RENIN INHIBITORS CONTAINING ALPHA-HETEROATOM AMINO-ACIDS AS P2 RESIDUES

被引：22

作者：

REPINE, JT

KALTENBRONN, JS

DOHERTY, AM

HAMBY, JM

HIMMELSBACH, RJ

KORNBERG, BE

TAYLOR, MD

LUNNEY, EA

HUMBLET, C

RAPUNDALO, ST

BATLEY, BL

RYAN, MJ

PAINCHAUD, CA

机构：

[1] WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES DIV, DEPT CHEM, ANN ARBOR, MI 48106 USA

[2] WARNER LAMBERT PARKE DAVIS, PARKE DAVIS PHARMACEUT RES DIV, DEPT PHARMACOL, ANN ARBOR, MI 48106 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 06期

关键词：

D O I：

10.1021/jm00084a008

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of renin inhibitors having alpha-heteroatom amino acids as P2 substitutions has been prepared. Examples where the heteroatom is oxygen, sulfur, or nitrogen are described. Many of the compounds exhibit subnanomolar potency when tested in vitro against monkey renin. When selected compounds were tested orally in conscious, salt-depleted, normotensive, Cynomolgus monkeys, low to moderate blood pressure lowering was observed. At an oral dose of 30 mg/kg, compound 53a lowered blood pressure by a maximum of 18 mmHg at 2.5 h post-dose.

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收藏

页码：1032 / 1042

页数：11

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