第八章心血管药物 cardiovascular drugs

第八章心血管药物Cardiovascular drugs

心血管药物 Cardiovascular drugs

第一节强心药 Cardiotonic agents

第二节抗心绞痛药 Antianginal drugs

第三节抗心率失常药 Antiarrhythmic drugs

第四节抗高血压药 Antihypertensive drugs

第五节降血酯药 Antilipidemic drugs

抗高脂蛋白血症药 Antihyperlipoproteinemic drugs

强心药 Cardiotonic agents正性肌力药 Inotropic agents

I 强心苷类 Cardiac glycosides

II 非苷类强心药


1 临床常用强心苷类

2 结构特征及构效关系

3 作用机制

4 代表药物

1 临床常用强心苷类－ 1

洋地黄毒苷 Digitoxin

地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3

H3C

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H


毛花苷 C Lanatoside C

毒毛花苷 K Strophanthin K

OHO

OHC

H3C

O O

OO

H3C OH

H

OOO

OCH3

H

OH

HOHO

HO

HOHO

HO

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OHOHOH

H

OH

CH3

HO

HOHO

HO

O


AacutearingAgravefrac14parafrac34UumlOtilde Convallatoxin

O O

OHC

H3C

OH

H

OH

OO

HO

HO

H3C

OH

H

2 结构特征及构效关系－ 1

1) 由糖苷基与配糖基两部分组成2) 糖苷基部分 ① 以 14- 糖苷键连接 ② 糖基本身并无活性失糖后配糖基 3-

OH 迅速转为 3-OH 而失活

常见糖苷基O

HOHO

HO

HO

OHO OH

H3C

OH

HO

O OHH3C

OCH3

HOO OHH3CHO

HOOH

-D-NtildeoacutemicroOslashraquoAEligparafrac34IgraveCcedil -D-AEligIumlIgraveNtildeIgraveCcedil

-L-EcircoacuteAgraveicircIgraveCcedil -D-frac14OacuteAumlAtildeoacuteAcirceacuteIgraveCcedil

2 结构特征及构效关系－ 23) 配糖基部分① 甾核立体构象顺－反－顺

OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D

2 结构特征及构效关系－ 3 ② 17 位 - 不饱和内酯环

卡烯内酯 Cardenolide 蟾二烯羟酸内酯 Bufadienolide

O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17


17 位 - 不饱和内酯环内酯环变为 17 位则活性降低双键被饱和或内酯环打开活性均显著降低

或消失不饱和氰基取代保留活性

2 结构特征及构效关系－ 5③ 羟基取代

通常 3 位有 OH 与糖苷基连接转为构型则失活

3

OH

CH3

H

CH3

HO

H

H

H


通常 14 位有 OH 若脱水成双键（ 814 or141

5 ）则失活 C14 应保持 sp3 杂化在甾核的其它位置上引入 OH

8

13

14

15

OH

CH3

H

CH3

HO

H

H

H

2 结构特征及构效关系－ 6④ 角甲基

通常 10 13 有两个甲基称 19-CH3 和 18-C

H3

19-CH3 氧化为 19-CH2OH 或 19-CHO 活性升高若氧化为 19-COOH 则活性大大降低

19-CH3 脱除活性大大降低10

13

18

19

OH

CH3

H

CH3

HO

H

H

H


⑤ 引入双键 56 和 1617 保留作用 89 丧失强心作用

56

89

16

17OH

CH3

H

CH3

HO

H

H

H

3 强心苷类作用机制抑制心肌细胞膜结合的 Na+K+-ATPase 使细胞内

Na+ 增多 K+ 减少并进一步导致细胞内 Ca2+ 增加使心肌收缩加强

强心苷类中毒引发心律紊乱可用钾盐防止或缓解

4 强心苷类代表药物

地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3

II 非苷类强心药1 磷酸二酯酶抑制剂 PDEI Phosphodiesterase inhibit

ors

2 1 受体激动剂 1-Adrenoceptor ago

nists

3 钙敏化药 Calcium sensitizers

1 磷酸二酯酶抑制剂类强心药－1

氨力农 Amrinone 米力农 Milrinone

HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS

依洛昔酮 Enoximone 匹洛昔酮 Piroximone


贝马力农 Bemarinone

维司力农 Vesnarinone

CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O

2 1 受体激动剂类强心药－ 1

多巴胺 Dopamine

多巴酚丁胺 Dobutamine

CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效


异波帕胺 Ibopamine

地诺帕明 Denopamine

CH2CH2NHCH2CHCH3O

CH3OOH

OH

CH2CH2NHCH3(CH3)2CHCO

(CH3)2CHCO

O

O

口服有效


扎莫特罗 Xamoterol

普瑞特罗 Prenalterol

HO OCH2 CH CH2NHCH(CH3)2

OH

HO OCH2 CH CH2NHCH2CH2NHC

OH

N

O

O

双重作用

选择性 1 受体激动剂

3 钙敏化剂类强心药

AEligyenAumlordfplusmnfrac12 Pimobendan

OgraveAacuteEumldivideAcirciacuteszligograve IsomazoleAacuteograveAcirciacuteszligograve Sulmazole

N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O







抗心绞痛药 Antianginal drugs

I 硝酸酯及亚硝酸酯类 Nitrates and nitrites

II 钙拮抗剂 Calcium antagonists

III - 受体阻断剂 -Blockers （见抗肾上腺素药物）

I 硝酸酯及亚硝酸酯类Nitrates and nitrites

发展作用比较作用机制代表药物

1 硝酸酯及亚硝酸酯类的发展－1

Icircigrave EumlAumlIumlotildeotildeyenPentaerythritoltetranitrate

paraiexcl EumlAumlIumlotildeotildeyenErythrityltetranitrate

IumlotildeEumlaacute EcircOacuteIacuteNitroglycerol

CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2

NtildeCcedilIumlotildeEumlaacuteOgraveigraveIcircigrave otildeyen Amyl nitriteCH3 CH

CH3

CH2 CH2ONO


microyenIumlotildeEumlaacuteOgraveigraveEacutefrac12AgraveaeligotildeyenIsosorbide mononitrate

IumlotildeEumlaacuteOgraveigraveEacutefrac12AgraveaeligotildeyenIsosorbide dinitrate

O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2


cedilEcircAcircparaAacuteugraveIumlotildeotildeyen Mannityl hexanitrate

C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO

2 硝酸酯及亚硝酸酯类作用比较

药物给药方式起效时间 min 作用时间 min

亚硝酸异戊酯吸入 05 1

硝酸甘油舌下 2 30

丁四硝酯口服 15 360

硝酸异山梨酯口服 15 560

戊四硝酯口服 20 5560

3 NO 舒张血管作用过程血管内皮细胞

合成并释放

血管内皮舒张因子 NO （ EDRF ）弥散

血管平滑肌细胞 NO激活

鸟苷酸环化酶

血管平滑肌松弛

肌球蛋白去磷酸化

蛋白激酶

cGMP

GMP

激活

3 硝酸酯及亚硝酸酯类作用机制

硝酸酯类硝酸酯受体（－ SH ）

（血管内皮细胞和血管平滑肌细胞）

NOSNO


硝酸酯受体 SH耗竭可产生耐受性给予硫醇保护剂可克服耐受性如 HSCH2CH(OH)CH(OH)CH2SH

4 硝酸酯及亚硝酸酯类代表药物硝酸异山梨酯 Isosorbide dinitrate

1436-Dianhydro-D-glucitol-25-dinitrate

爆炸性水解性

常温干燥稳定遇酸碱热易水解

6

54

3

2

1O

O

H

H

O2NO

ONO2


1 作用与临床应用

2 结构类型

1 钙拮抗剂的作用与临床应用

① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用

2 钙拮抗剂的结构类型

① 二氢吡啶类 Dihydropyridines DHP

② 芳烷基胺类 Aralkylamines

③ 苯并硫氮杂卓类 Benzothiazepines

④ 二苯基哌嗪类 Diphenylpiperazines

⑤ 其它类

二氢吡啶类钙拮抗剂－ 1

NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X

硝苯地平 Nifedipin

eCH3 CH3 CH3 2-NO2

尼群地平 Nitrendi

pineC2H5 CH3 CH3 3-NO2

尼索地平 Nisoldipi

neCH3 CH2CH(CH3)2 CH3 2-NO2

尼鲁地平 Niludipi

neCH2CH2OC3H7 CH2CH2OC3H7 CH3 3-NO2


药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod

ipineCH(CH3)2 CH2CH2OCH3 CH3 3-NO2

非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod

ipineCH3 C2H5 CH2OCH2CH2NH2 2-Cl

CH2CH2NCH2C6H5

CH3

二氢吡啶类的构效关系－ 11 14- 二氢吡啶环是必须结构氧

化为吡啶作用消失还原双键作用减弱

2 二氢吡啶环上的 NH 不被取代可保持最佳活性

3 26 位取代基应为低级烷烃4 35 位羧酸酯基优于其它基团且

两个酯基不同者优于相同者可容纳较大基团主要影响血管选择性和作用时间

NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3

二氢吡啶类的构效关系－ 2

5 4 位主要影响作用强度以取代苯基为宜且苯环的邻间位吸电子基取代增强活性对位取代则活性降低或消失

6 S 构型体活性较强7 苯环平面与二氢吡啶环平面的扭角越小活性越强

NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3

硝苯地平 Nifedipine 14-Dihydro-26-dimethyl-4-(2-ni

trophenyl)-35-pyridinedicarboxylic acid dimethyl ester

临床用于预防和治疗冠心病心绞痛抗高血压但不用于抗心律失常

2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2

芳烷基胺类钙拮抗剂－ 1

OgraveAgraveAumlordfAringAacuteAtildetimes Emopamil(-) gt (+)

R=H IcircnotAgrave AringAacuteAtildetimes Verapamil (_) EcircOgraveEacuteIumlETHOcircETHAumlpara sup1yacute EumlUgrave (+) ETHAumlfrac12EcircIacuteacute

R=OCH3 cedilecirc AcircaringAringAacuteAtildetimes Gallopamil (-)

NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN


middotuml AgraveucircAringAacuteAtildetimesFalipamil

agraveccedilAringAacuteAtildetimesTiapamil

O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S

维拉帕米 Verapamil

5-[(34-Dimethoxyphenethyl)methylamino]-2-(34-dimethoxyphenyl)-2-isopropyl

valeronitrile

抗室上性心动过速等抗心绞痛

H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3

苯并硫氮杂卓类钙拮抗剂

AumlaacuteiquestEumlAacuteogravetimesiquestNictiazemN

R=

R=CH3 microOslashparaucircAacuteogravetimesiquest Diltiazem

N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45

抗各型心绞痛首过效应明显

地尔硫卓的体内代谢脱 O －甲基

脱乙酰基

脱 N －甲基 NHCH3

N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH

二苯基哌嗪类钙拮抗剂

X=H 桂利嗪 Cinnarizine

X=F 氟桂利嗪 Flunarizine

利多氟嗪 Lidoflazine

X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F

其它类钙拮抗剂－ 1

szligszligiquestEumlIcircocircAacuteOumlPerhexiline

UumlETHAEligOtildemicroOslashparaucircBepridil

CHCH2

NH

CH2 N CH2CHCH2OCH2CH(CH3)2

N


AEligOtildeAumlaacuteAgrave AtildedividePrenylamine

middotOgravemicroOslashAacuteOuml Fendiline

CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3







抗心率失常药 Antiarrhythmic drugs

1 作用2 分类3 发展4 构效关系

1 心肌细胞膜电位与离子转运

零电位

阈电位静息电位

动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+

iquestccedilAumlcurrenmicroccedilIcircraquomv

-100

-80

-60

-40

-20

0

+20

cedilacute frac14laquo raquomacr

Egraveyenfrac14laquoraquomacr

4

3

2

1

0

-

-

-

-

-

-

-

2 抗心率失常药的分类－ 1

传统分类 I 类钠通道阻滞剂 IA IB IC

II 类 - 受体拮抗剂 III 类延长动作电位时程药物 IV 类钙拮抗剂


按作用机制分类离子通道阻断剂

bull 钠通道阻断剂bull 钾通道阻断剂bull 钙拮抗剂

- 受体拮抗剂

3 钠通道阻断剂 IA 类膜稳定剂－1

N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH

iquestuumlAumlaacuteparaiexcl Quinidine (+)8S9S

iquestuumlAumlthorn Quinine (-)8S9R

Quinidine 的体内代谢

9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

3 钠通道阻断剂 IA 类－ 2

AEligOtildeAcircsup3iquestuml OgraveograveProcaine

H2N CNHCH2CH2N(C2H5)2

O

H2N COCH2CH2N(C2H5)2

O

AEligOtildeAcircsup3iquestuml OgraveogravedegmiddotProcainamide


degcentOgravearingAcirciacuteAacuteOuml Ajmaline

C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2

plusmnucircszligAacutedegmiddot Disopyramide

N NOH

C2H5

OH

CH3


szligAacuteAtildeAgraveAringmicroPirmenol

Icircdivideplusmnfrac12szligograveAacuteOumlCibenzoline

N

NH

OH

CH2CH2CH2 N

H3C

H3C

3 钠通道阻断剂 IB 类提高颤动阈值－1

R 药名

NHCOCH2N(C2H5)2 利多卡因 Lidocaine

NHCOCH(CH3)NH2 妥卡胺 Tocainide

OCH2CH(CH3)NH2 美西律 Mexiletine

NHCONH(CH2)3NHCH(CH3)2 瑞卡南 Recainam

NHCOCH2N+(CH3)(C2H5)2Cl-

甲基利多卡因 Methyllidocai

ne

CH3

R

CH3

神经细胞膜稳定作用

3 钠通道阻断剂 IB 类－ 2

AumlordfAgravetimesIcircdivideagraveordm Moricizine

N

S

COCH2CH2N

NHCOOC2H5

O

IB IC 类抗心律失常作用扩张冠脉解痉

3 钠通道阻断剂 IC 类减慢传导－1

middotuacute iquestuml AumlaacuteFlecainide

paradivideiquestuml AumlaacuteEncainide

NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3

3 钠通道阻断剂 IC 类－ 2

OacutecentmicroOslashiquestuml AumlaacuteIndecainide

AgraveIacuteiquestuml AumlaacuteLorcainide

Cl N N

COCH2

CH(CH3)2

H2NOC (CH2)3NHCH(CH3)2


sup3pound iquestcopyszligoslashPyrozolin

AEligOtildeAcircTHORNAringAacuteIacuteordfPropafenone

COCH2CH2

OCH2CHCH2NH(CH2)2CH3

OH

N

N

NH OH

CH2

CH2

N

N

4 钾通道阻断剂－ 1

OgraveOgraveotildepoundiquestuml AumlaacuteAcecainide

degmiddot microacircIacuteordfAmiodarone

CONHCH2CH2N(C2H5)2CH3CONH

O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5


AtildeAgraveszligszligAcirciexcl Melperone

frac14timesNtildeotildeplusmnfrac12Iacuteiexcl Meobentine

F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3


aumlaringUumlETHdegmiddot Bretylium tosylate

CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-

选择性作用于心肌钾离子通道致心律失常副作用较小

5 离子通道阻断剂类抗心率失常药的构效关系

芳香环或环系插入膜磷酯的烷基链中芳环上可带有不同取代基脂溶性越大活性越强

氨基（阳离子）与膜多肽的阴离子基结合氮上取代基可相同可不同 X Y 为可形成氢键的极性取代基与膜磷酯的极性端形成氢键立体化学对活性的影响要具体分析

X (CH2)2 N+H

Y

R

R







抗高血压药物的作用部位和机理

紧张脑

神经节

肾脏心输出量增加

血流量增加

血管收缩

肾素血管紧张素 I

血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加

抗高血压药 Antihypertensive drugs

I 作用于自主神经系统的药物

II 影响 RAS 系统的药物

III 作用于离子通道的药物

IV 利尿药及其它药物

I 作用于自主神经系统的抗高血压药1 作用于神经末梢的药物

2 作用于中枢神经系统的药物

3 作用于毛细小动脉的药物

4 神经节阻断药

5 肾上腺素能受体拮抗剂

1 作用于神经末梢的抗高血压药 -1

NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21

AgraveucircEacuteaacuteAEligfrac12 Reserpine

NH

N

HNH

N

H

CH3O

microOslashEacuteaacuteAEligfrac12 Deserpidine AtildeAgraveEumldivideEacuteaacuteAEligfrac12 Methoserpidine

阻止囊泡再摄取


胍乙啶 Guanethidine

胍那佐啶GuanazodineNH

CH2NH C NH2

NH

N CH2CH2NH C NH2

NH

进入囊泡置换去甲肾上腺素

利舍平 Reserpine

结构特点六个不对称碳原子整个分子呈左旋性 15 16 20 位的 H都是顺式为型 17 位的 OCH3 为型 16 18 位的取代基是顺式为型 3-H差向异构后失效

21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

利舍平 Reserpine 具有弱碱性 pKb=66 溶于醋酸易氧化变质先生成 34- 二去氢利舍平（黄绿色荧光）再生成 3456- 四去氢利舍平（蓝色荧光）进一步氧化则生成黄褐色的聚合物宜避光避热保存

具酯类结构酸碱可促其水解碱性水解断裂两个酯基生成利舍平酸仍有活性

具吲哚生物碱的呈色反应对轻中度的早期高血压疗效显著作用温和持久具中枢镇静镇痛作用

2 作用于中枢神经系统的抗高血压药 -1

bull 中枢受体激动剂bull 因分子中有两个相邻的酚羟基易氧化变色故制剂

中常加入还原剂以增加稳定性同时应避光保存bull 在碱性溶液中更易氧化氧化中因形成吲哚醌类而使溶液颜色逐渐变深后者进一步聚合生成黑色聚合物

bull 与水合茚三酮反应显蓝紫色bull 属中强度降压药

HO

HO

OH

O

H2N CH3

甲基多巴Methyldopa


AumlordfEumldivideAumlaacuteparauml Moxonidine IR1 (+)

N

N

Cl

CH3O

NHH3C

HN

N

iquestEacuteAgraveOumlparauml Clonidine IR1 (+) frac12microNtildesup1

2 (+) cedilplusmntimesdivideOacuteAtilde

NH

HN

N

Cl

Cl

（中枢镇静）

3 作用于毛细小动脉的抗高血压药－ 1

sup2frac14Ccediluacuteagraveordm BudralazineIacuteETHCcediluacuteagraveordm Todralazine

EumllaquoeumlAcircCcediluacuteagraveordm DihydralazineeumlAcircCcediluacuteagraveordm Hydralazine

N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2


sup3curren acuteordm degmiddot Vincamine

microOslashdegIacute szligograve Dibazole

paradivideCcediluacuteagraveordm Endralazine

NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管


Aacuteugravefrac14timesaumlaringiumlsect Hexamethonium bromide

2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3

AtildeAgraveiquestuml Agrave Atildedivide Mecamylamine

CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂

II 影响 RAS 系统的抗高血压药

肾素－血管紧张素－醛固酮系统

Renin-angiotensin-aldosterone system RAS or RA

AS

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Leu-Val-Tyr-Ser血管紧张素原 Angiotensinogen

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu血管紧张素 I Angiotensin I

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe血管紧张素 II Angiotensin II

血管收缩血压升高

醛固酮 Aldosterone 血容量增加

肾素 Renin

血管紧张素转化酶 ACEAngiotensin-converting enzyme

Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg舒缓激肽 Bradykinin

Arg-Pro-Pro-Gly-Phe-Ser-Pro

血压下降

ACE

血管舒张


血管紧张素转化酶抑制剂 ACEI

肾素抑制剂

血管紧张素 II 受体拮抗剂

血管紧张素转化酶抑制剂 -1

degcentAgrave AEligOtildeAgraveucircAlaceprilCH2 CH

CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5

iquestuml IacuteETHAEligOtildeAgraveucircCaptoprilCH2 CH

CH3

C

O

N COOHHS

IgraveaeligAEligOtildeAcircTHORNeumlAuml Teprotide

Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro


AgravemicroAringmicroAEligOtildeAgraveucircLisinopril

H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH

OgraveAgraveAumlCcedilAEligOtildeAgraveucircEnalaprilCH C

O

N COOH

CH3

NHCH2CH2CH

COOC2H5


AgravetimesAtildetimesAEligOtildeAgraveucircRamipril

AcircYacuteAEligOtildeAgraveucircSpirapril

NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S


IcircdivideAgrave AEligOtildeAgraveucircCilazapril

agrave AumlCcedilAEligOtildeAgraveucircQuinapril

N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5

卡托普利 Captopril

分子中有两个不对称碳原子呈左旋性为 SS 构型不稳定见光或在水溶液中易氧化生成二硫化物鉴别与亚硝酸作用生成亚硝酰硫醇酯呈红色

用于高血压和充血性心力衰竭副作用皮疹味觉消失咳嗽

CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O

雷米普利 Ramipril

2S-[1[R(R)]23a6a]]-1-[2-[[1-(Ethoxycarbonyl)-3-

phenylpropyl]amino]-1-oxopropyl]octahydrocyclopenta[b]pyrrole-2-

carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038

Ntildeordfsup1Uumlfrac12ocircOtildeAringEumlOslashOcirc Angiotensinogen

NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph

CH CHCH2NHCHCONHCONHCHCONHCHCOOH

Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2

Pro - His - Pro - Phe - His - Phe - Phe - Val -Tyr

Asp - Arg - Val - Tyr - Ile - His - Pro - Phe - His - Leu - Leu - Val - Tyr - Ser

OgraveOumlmicrodegdegtimesAtildecedilEumlOslashPepstatin

CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3


AcircEgraveEacutesup3Igravesup1Losartan

Eacutesup3Agrave ETHAcirc Saralasin

Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N

Sar - Arg - Val - Tyr - Val - His - Pro - Ala


N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O

伊贝沙坦 Irbesartan 坎地沙坦 Candesartan


HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH

依普沙坦 Eprosartan

替米沙坦 Telmisartan

III 作用于离子通道的抗高血压药

钙拮抗剂

钾通道开放剂

钾通道开放剂－ 1 舒张血管平滑肌

抗高血压抗心绞痛对心肌缺血的保护作用治疗外周血管阻塞性疾病

抗哮喘对抗平滑肌过敏反应和治疗肌疲劳尿频尿急

钾通道开放剂－ 2

AtildetimesAringmicromicroOslashparaucircMinoxidil

N N

N

NH

OH

NH2

parathornmicroordf agraveordmDiazoxide

N

NHSCl

CH3

O O


EacutelaquoAcircuacuteiquestuml AacuteOumlCormakalin

szligAacuteAumlCcedilmicroOslashparaucircPinacidil

N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH








血浆脂蛋白 Lipoprotein 血脂包括胆固醇胆固醇酯甘油三酯磷酯及游离脂肪酸

结合成脂蛋白于血液中运转脂蛋白分为五种

乳糜微粒 CM 极低密度脂蛋白 VLDL 中等密度脂蛋白 IDL 低密度脂蛋白 LDL 高密度脂蛋白 HDL

降血酯药 Antilipidemic drugs

分类及发展苯氧乙酸类及其构效关系烟酸类羟甲戊二酰辅酶 A还原酶抑制剂类其它类

苯氧乙酸类降血酯药及其构效关系－ 1

1 羧基或易于水解的烷氧羰基是具有活性的必要条件2 脂肪酸部分的季碳原子并非活性必需只有一个烷基取代

亦有活性

AcircEgraveplusmnacute paraiexcl otildeyenClofibrate

OCl C COOC2H5

CH3

CH3


3 分子的芳基部分保证了亲脂性并能与蛋白质链某些部分互补增加苯基数目活性有增强的趋势

middotCcedilAringmicroplusmnacuteIgraveOslashFenofibrate

UumlETHAcircEgraveplusmnacuteIgraveOslashBeclobrate

Cl CH2 O C COOC2H5

C2H5

CH3

Cl CO O C COOCH(CH3)2

CH3

CH3


4 大部分有效药物在苯环对位或者烷基或芳烷基取代基上有氯但若以其它基团置换降脂活性并无改变取代基也并非必须在对位

frac14ordfmiddotCcedilplusmnacuteAEligeumlGemfibrozil

H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3


5 芳环对位的其它取代基特别是环烷基能增强对乙酰辅酶 A羧化酶的抑制降低或完全控制游离脂肪酸的合成

YacuteAacutemiddotOacuteAEligfrac12NafenopinO C

CH3

CH3

COOH


6 在氯贝丁酯的碳原子上再引入其它芳基或芳氧基取代基也能显著降低甘油三酯水平

AgraveucircplusmnacuteIgraveOslashLifibrate

OCl

CHCOO N CH3

OCl


7 以硫取代芳基与羧酸之间的氧可以提高降血脂作用

AEligOtildeAcircTHORNsup2frac14iquestfrac14Probucol

C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH

烟酸类降血酯药－ 1

1环上取代物

NtildeIgraveEumlaacute Nicotinic acidN

COOH

5pound middotuacuteNtildeIgraveEumlaacute 5-Fluoronicotinic acid

N

COOHF


2酯类前药

R =

Icircigrave EumlAumlNtildeIgraveotildeyen Niceritol NtildeIgraveEumlaacutefrac14iexcl frac14otildeyen Inositol nicotinate

OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O

烟酸类降血酯药－ 33烟酸类似物

4与苯氧乙酸类拼合物

degcentIcircocircAumlordfEumlfrac34 AcipimoxN

N

CH3

COOH

O

OgraveAgraveIacuteETHplusmnacuteIgraveOslashEtofibrate

N

COO(CH2)2OOCC O

CH3

CH3

Cl

羟甲戊二酰辅酶 A还原酶抑制剂HMG-CoA reductase inhibitors

羟甲戊二酰辅酶 A还原酶是体内胆固醇生物合成的限速酶

羟甲戊二酰辅酶 A还原酶抑制剂可有效降低体内胆固醇水平用于治疗高胆固醇血症

有一定的肝脏毒性

Acetyl-CoA

Acetyl acetyl-CoA

HMG-CoA 羟甲戊二酰辅酶 A

Mevalonate 甲羟戊酸

Isopentenyl pyrophosphate Isopentenyl adenine

Farnesyl pyrophosphate Coenzyme ADolichol

Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O

HMG-CoA还原酶抑制剂 -1

AtildeAgravemiddotyen EumlucircIacuteiexcl Mevastatin

O

CH3

H3C

O

HCH3

O

OHO

Acircaringmiddotyen EumlucircIacuteiexcl Lovastatin

O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5


ETHAacutemiddotyen EumlucircIacuteiexcl Simvastatin

OH3C

O

HCH3

O

OHO

H3C

H3C CH3

AEligOtildemiddotyen EumlucircIacuteiexcl Pravastatin

OCH3

H3C

O

HCH3

COOHHO

HO

OH


middotuacute middotyen EumlucircIacuteiexcl Fluvastatin

N

F

CHCH3

CH3

COOHHO

OH

HMG-CoA还原酶抑制剂的构效关系 8 位侧链碳为手性碳 R 和 S 构

型的活性相同该碳上再引入一个甲基活性增强引入其它烷基都不如甲基去甲基或将甲基移到位活性都下降

疏水部分最好具有平面性 1 位侧链内酯或羟基酸是活性中心 3和 5任一羟基酰化后活性都

大大降低 C3和 C5相对构型（顺式）及绝对构型（ RR）为最大活性所必须

5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO

西立伐他汀 Cerivastatin

因毒性太大引起横纹肌溶解已被 FDA撤销

COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3

不饱和脂肪酸类降血酯药

CH3(CH2)7CH=CH(CH2)7COOH OacuteIacuteEumlaacutepounduml 18Cpoundcopy Olic acid

CH3CH2(CH=CHCH2)3(CH2)6COOH NtildeCcedilAcirceacuteEumlaacutepounduml 18Cpoundcopy Linolenic acid

CH3(CH2)4(CH=CHCH2)3(CH2)3COOH frac14OacuteAumlordfAumlaacuteiquestEumlEumlaacutepounduml 18Cpoundcopy Gamolenic acid

CH3(CH2)4(CH=CHCH2)4CH2CH2COOH raquouml EacuteuacuteEumlAumlIumlcopyEumlaacutepounduml 20Cpoundcopy Arachidonic acid

CH3(CH2)4(CH=CHCH2)2(CH2)6COOH NtildeCcedilOacuteIacuteEumlaacutepounduml 18Cpoundcopy Linolic acid

阴离子交换树脂类降血脂药吸附肠内胆酸加速胆固醇分解排泄

降胆敏（降脂树脂 1号 Cholestyramine ）降胆宁（降脂树脂 2号 Colestipol ）降胆葡胺（降脂树脂 3号 DEAE Sephadex ）

iquestfrac14AgraveacuteIumlcopydegmiddotCholestyramine

CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表

心血管药物要求－ 1 掌握

心血管药物按临床治疗疾病的分类及各类药物的类型强心苷类的结构特点及构效关系钙拮抗剂的类型及二氢吡啶类的构效关系 ACEI 的作用及结构特点硝酸异山梨酯硝苯地平维拉帕米普鲁卡因胺甲

基多巴卡托普利氯贝丁酯的结构化学名称性质及应用

心血管药物要求－ 2 熟悉

硝酸酯类药物的作用机制及特点磷酸二酯酶抑制剂的作用抗高血压药物的作用环节苯氧乙酸类降酯药的结构特点及构效关系米力农尼卡地平地尔硫卓胺碘酮可乐定雷米

普利吉非贝齐烟酸辛伐他汀的结构名称和应用

心血管药物要求－ 3 了解

心肌动作电位过程与抗心率失常药的作用 HMG － CoA还原酶抑制剂的作用及构效关系地高辛硝酸甘油桂利嗪奎尼丁溴苄胺利舍平依那普利氯沙坦氟伐他汀的结构名称和应用

1048698谢谢

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3 作用机制

4 代表药物



地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3

H3C

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H




OHO

OHC

H3C

O O

OO

H3C OH

H

OOO

OCH3

H

OH

HOHO

HO

HOHO

HO

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OHOHOH

H

OH

CH3

HO

HOHO

HO

O



O O

OHC

H3C

OH

H

OH

OO

HO

HO

H3C

OH

H




常见糖苷基O

HOHO

HO

HO

OHO OH

H3C

OH

HO

O OHH3C

OCH3

HOO OHH3CHO

HOOH




OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 131



地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3

H3C

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H




OHO

OHC

H3C

O O

OO

H3C OH

H

OOO

OCH3

H

OH

HOHO

HO

HOHO

HO

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OHOHOH

H

OH

CH3

HO

HOHO

HO

O



O O

OHC

H3C

OH

H

OH

OO

HO

HO

H3C

OH

H




常见糖苷基O

HOHO

HO

HO

OHO OH

H3C

OH

HO

O OHH3C

OCH3

HOO OHH3CHO

HOOH




OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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OHO

OHC

H3C

O O

OO

H3C OH

H

OOO

OCH3

H

OH

HOHO

HO

HOHO

HO

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OHOHOH

H

OH

CH3

HO

HOHO

HO

O



O O

OHC

H3C

OH

H

OH

OO

HO

HO

H3C

OH

H




常见糖苷基O

HOHO

HO

HO

OHO OH

H3C

OH

HO

O OHH3C

OCH3

HOO OHH3CHO

HOOH




OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131



O O

OHC

H3C

OH

H

OH

OO

HO

HO

H3C

OH

H




常见糖苷基O

HOHO

HO

HO

OHO OH

H3C

OH

HO

O OHH3C

OCH3

HOO OHH3CHO

HOOH




OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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常见糖苷基O

HOHO

HO

HO

OHO OH

H3C

OH

HO

O OHH3C

OCH3

HOO OHH3CHO

HOOH




OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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OH

CH3

H

CH3

HO

H

H

H

cis-trans-cis

19

18

17

1615

14

131211

10 98

765

43

2

1

A

BC

D



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131



O O

OH

R

HO

O O

19

18

17 16

1514

13

1211

109

8

76

54

3

21

A B

C D

20

21

22

23 24

2322

21

20

17






3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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3

OH

CH3

H

CH3

HO

H

H

H




8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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8

13

14

15

OH

CH3

H

CH3

HO

H

H

H



H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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H3



13

18

19

OH

CH3

H

CH3

HO

H

H

H



56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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56

89

16

17OH

CH3

H

CH3

HO

H

H

H





地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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地高辛 Digoxin

H3C

O O

OO

H3C OH

H

H

OO

H3CO

O

H3C

OH

HO

OHOH

H

OH

CH3


ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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ors


nists




HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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HN

N

NC

O

CH3HN

N

H2N

O

NH

NH

CON

O

CH3CH2

NH

NH

CO

O

H3C

H3CS





CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH3O

CH3OCON N

NH

O

N

NH

OCH3 CH3

CH3O

O


多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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多巴胺 Dopamine


CH2CH2NHHO

HO

CH CH2

CH3

CH2 OH

CH2CH2NH2HO

HO

口服无效




CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH2CH2NHCH2CHCH3O

CH3OOH

OH


(CH3)2CHCO

O

O

口服有效





OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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OH


OH

N

O

O

双重作用





N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

NH

CH3 N NH

O

CH3

NN

HN

S

OCH3

CH3

O

N

HN

S

OCH3

CH3

O

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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Slide 131

















CH2ONO2

CHONO2

CH2ONO2

CH2ONO2

CHONO2

CHONO2

CH2ONO2

CH2ONO2

C

CH2ONO2

O2NOCH2 CH2ONO2


CH3

CH2 CH2ONO




O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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O

O

H

H

O2NO

OH

O

O

H

H

O2NO

ONO2



C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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C

C

ONO2

C

CH2ONO2

C

ONO2

CH2ONO2

H

H

H

H

O2NO

O2NO









合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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合成并释放



鸟苷酸环化酶



蛋白激酶

cGMP

GMP

激活




NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NOSNO





爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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爆炸性水解性


6

54

3

2

1O

O

H

H

O2NO

ONO2



2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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2 结构类型


① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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① 抗心绞痛

② 抗心率失常

③ 抗高血压

④ 其它作用






⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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⑤ 其它类


NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3


药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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药名 R1 R2 R3 X


eCH3 CH3 CH3 2-NO2








药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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药名 R1 R2 R3 X

尼卡地平 Nicard

ipineCH3 CH3 3-NO2

尼莫地平 Nimod


非洛地平 Felodi

pineC2H5 CH3 CH3

2-Cl 3-

Cl

氨氯地平 Amlod


CH2CH2NCH2C6H5

CH3






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 131






NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NH

R1OOCH

COOR2

H3C R3

X

12

34

5

6

2

3




2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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2

6

54

3

21

NH

H3COOCH

COOCH3

H3C R3

NO2





NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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NCH(CH3)2

CH3O

CH3O

CH3 CN

R

OCH3

OCH3

NCH(CH3)2

CH3 CN




O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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O2

N NCH3O

CH3O

CH3

O

OCH3

OCH3

NCH3O

CH3O

CH3

OCH3

OCH3

S

O2S



valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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valeronitrile


H3CO

H3CO

N

CH3 CN

CH(CH3)2

OCH3

OCH3



R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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R=


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C

O

R1 2

3

45



脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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脱乙酰基


N

SH

H

O

CH2CH2N(CH3)2

OCH3

O C CH3

O

OH

OH





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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Slide 131





X

N N CH2 CH CHCH

X

N N CH2CHCH2CH2 NH

H3C

H3C

C

OF

F




CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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CHCH2

NH


N




CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CHCH2CH2NHCHCH2

CH3

CHCH2CH2NHCH

CH3










零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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零电位


动作电位

细胞膜 +_+_+_+_+_+_+_+_

+_

+_

+_

+_

+

_

+

_+_+__+

Na+ K+-ATPase

ATP Na+

K+Ca++Cl-Na+

K+K+


-100

-80

-60

-40

-20

0

+20



4

3

2

1

0

-

-

-

-

-

-

-







- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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- 受体拮抗剂


N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

HCHCH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OOH

HH




9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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9

4

87

6

54 3

2

1

8

7

6

5

3

2

1N

HCHCH2

N

CH3OH

HOH N

HCHCH2

N

CH3OH

HOH

HO

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HCHCH2

N

CH3OH

HOH

OH

1

2

3

5

6

7

8

12

345

6

78

4

9

N

HCHCH2

N

HOH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9

N

HHOCH2CH2

N

CH3OH

HOH

1

2

3

5

6

7

8

1

2

345

6

78

4

9




O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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O


O




C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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Slide 131



C CH2CH2NH2NCO

N

CH(CH3)2

CH(CH3)2


N NOH

C2H5

OH

CH3




N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

NH

OH

CH2CH2CH2 N

H3C

H3C


R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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R 药名







ne

CH3

R

CH3




N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

S

COCH2CH2N

NHCOOC2H5

O





NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NHCO

CH2CH2

OCH3

N

CH3

NH

CH2NHCO

OCH2CF3

OCH2CF3




Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

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Cl N N

COCH2

CH(CH3)2





COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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COCH2CH2


OH

N

N

NH OH

CH2

CH2

N

N





O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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O

C

O

OCH2CH2N

(CH2)3CH3

I

I

C2H5

C2H5




F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

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F COCH2CH2CH2 N CH3

CH2NHCCH3ON

NHCH3

CH3



CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH2 N+ CH2CH3

CH3

CH3BrCH3 SO3

-





X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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X (CH2)2 N+H

Y

R

R








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 131








紧张脑

神经节


血流量增加

血管收缩


血管紧张素 II

醛固酮

增大血容积

高血压

外周阻力增加












NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3

12

34

56

789

10

11

1213

141516

17

18

1920

21


NH

N

HNH

N

H

CH3O






CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH2NH C NH2

NH

N CH2CH2NH C NH2

NH


利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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利舍平 Reserpine


21

2019

18

17

1615

14

1312

11

10

98 7

65

43

21NH

NCH3O

H

H

H

OCH3

CH3OOC OOC

OCH3

OCH3

OCH3








HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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HO

HO

OH

O

H2N CH3




N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

N

Cl

CH3O

NHH3C

HN

N



NH

HN

N

Cl

Cl

（中枢镇静）




N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

N

NHNH2

N

N

NHNH2

NHNH2

N

N

NHNHCOOC2H5

N

N

NHN CCH3

CH C(CH3)2





NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NN

C2H5CH3OC

HO

O

NN

N NHNH2PhCO

NH

NCH2

扩张脑血管



2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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2Br-H3C N+ (CH2)6

H3C

H3C

N+ CH3

CH3

CH3


CH2

CH3

CH3

CH3

NHCH3

HCl


1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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1 - 受体拮抗剂

- 受体拮抗剂




AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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AS






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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肾素抑制剂




CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH3

C

O

N CONHCHCOOHCH3CS

O

CH2C6H5


CH3

C

O

N COOHHS





H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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H2N(CH2)3CH2

CH C

O

N COOHNHCH2CH2CH

COOH


O

N COOH

CH3

NHCH2CH2CH

COOC2H5




NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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NCOOH

CO HN Ph

COOC2H5CH3

OCN

HOOC

NH

Ph

CH3C2H5OOC

S

S




N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

N

NH

O

CH

COOH

PhCH2CH2

COOC2H5

N

HOOC

CCH

O

NHCHCH2CH2

CH3

COOC2H5




CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH2 C C

O

NHS

HCOOH

H3C

CH2 C C

O

NS

HCOOH

H3C

N

O




carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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carboxylic acid

(R) NH

(R)

CH3

N

O

(S) (S)

(S)C2H5O O

HOOC

H

H1

2 3

3a4

56

6a






肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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肾素 Renin




血压下降

ACE

血管舒张



肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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肾素抑制剂


肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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肾素抑制剂

U-71038


NCONH CHCONHCH

COOC(CH3)3

CONH

CH2Ph


Bu-i OH Pr-i CH

CH2COOH

CH3

OC2H5

N

N

CH3

CH2




CHCH2C Val

O

ValCH3

StaCH3

Ala Sta OH

Sta= COCH2CHCHCH2CH

OH

NH2

CH3

CH3




Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Sar = Gly(Me)

N

NCH2OHCH3(CH2)3

Cl

NH

NN

N



N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

NH3C

NN

HN N

ON

N

ONN

HN N

CH3

HO O



HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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HOOC

N

NH3C

COOHS

N

N

N

N

CH3

CH3

CH3

COOH




钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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钙拮抗剂

钾通道开放剂






N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N N

N

NH

OH

NH2


N

NHSCl

CH3

O O




N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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N

NHC NCHC(CH3)3

NHCN

CH3

O

N

NC

CH3

CH3

O

OH















亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

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Slide 112

Slide 113

Slide 114

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亦有活性


OCl C COOC2H5

CH3

CH3





Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

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Slide 113

Slide 114

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Cl CH2 O C COOC2H5

C2H5

CH3


CH3

CH3




H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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H3C

CH3

OCH2CH2CH2C COOH

CH3

CH3




CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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CH3

CH3

COOH




OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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OCl

CHCOO N CH3

OCl




C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 102

Slide 103

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C SS

CH3

CH3

OH

C(CH3)3

C(CH3)3

(CH3)3C

(CH3)3C

HO

CHS

CH3

(CH3)3C

(CH3)3C

HO COOH


1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 103

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Slide 107

Slide 108

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1环上取代物


COOH


N

COOHF


2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

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Slide 2

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Slide 51

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Slide 101

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Slide 103

Slide 104

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Slide 106

Slide 107

Slide 108

Slide 109

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Slide 113

Slide 114

Slide 115

Slide 116

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2酯类前药

R =


OR

OR

OR

OR

RO

RO

CROCH2

ROCH2

CH2OR

CH2OR

N

C

O




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

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Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

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Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

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Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

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Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

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Slide 121

Slide 122

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Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131




N

CH3

COOH

O


N

COO(CH2)2OOCC O

CH3

CH3

Cl





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

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Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

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Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131





Acetyl-CoA

Acetyl acetyl-CoA





Cholesterol

HMG-CoA reductase

C OHH3C

HOSCoA

O

O

C OHH3C

HOOH

O



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131



O

CH3

H3C

O

HCH3

O

OHO


O

CH3

H3C

O

HCH3

H3C

O

OHO

1

2

345

6

7 8

3

5



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131



OH3C

O

HCH3

O

OHO

H3C

H3C CH3


OCH3

H3C

O

HCH3

COOHHO

HO

OH



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131



N

F

CHCH3

CH3

COOHHO

OH





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131





5

3

87

65 4

3

2

1

O

CH3

H3C

O

HCH3

H3C

O

OHO



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131



COOHHO

OH

N

CH3

CH3

F

H3CO

H3C CH3










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

Slide 14

Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131










CH CH2 CH CH2

CH2N+(CH3)3CH2CHn

nCl-

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

Slide 13

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Slide 15

Slide 16

Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

Slide 60

Slide 61

Slide 62

Slide 63

Slide 64

Slide 65

Slide 66

Slide 67

Slide 68

Slide 69

Slide 70

Slide 71

Slide 72

Slide 73

Slide 74

Slide 75

Slide 76

Slide 77

Slide 78

Slide 79

Slide 80

Slide 81

Slide 82

Slide 83

Slide 84

Slide 85

Slide 86

Slide 87

Slide 88

Slide 89

Slide 90

Slide 91

Slide 92

Slide 93

Slide 94

Slide 95

Slide 96

Slide 97

Slide 98

Slide 99

Slide 100

Slide 101

Slide 102

Slide 103

Slide 104

Slide 105

Slide 106

Slide 107

Slide 108

Slide 109

Slide 110

Slide 111

Slide 112

Slide 113

Slide 114

Slide 115

Slide 116

Slide 117

Slide 118

Slide 119

Slide 120

Slide 121

Slide 122

Slide 123

Slide 124

Slide 125

Slide 126

Slide 127

Slide 128

Slide 129

Slide 130

Slide 131

抗心绞痛药

阻断

钙拮

抗剂

硝酸酯类

发展

机制代

表









1048698谢谢

Slide 1

Slide 2

Slide 3

Slide 4

Slide 5

Slide 6

Slide 7

Slide 8

Slide 9

Slide 10

Slide 11

Slide 12

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Slide 17

Slide 18

Slide 19

Slide 20

Slide 21

Slide 22

Slide 23

Slide 24

Slide 25

Slide 26

Slide 27

Slide 28

Slide 29

Slide 30

Slide 31

Slide 32

Slide 33

Slide 34

Slide 35

Slide 36

Slide 37

Slide 38

Slide 39

Slide 40

Slide 41

Slide 42

Slide 43

Slide 44

Slide 45

Slide 46

Slide 47

Slide 48

Slide 49

Slide 50

Slide 51

Slide 52

Slide 53

Slide 54

Slide 55

Slide 56

Slide 57

Slide 58

Slide 59

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第八章 心血管药物 cardiovascular drugs

Documents

第八章心血管药物 cardiovascular drugs