SYNTHESES AND BIOLOGICAL-ACTIVITIES OF POTENT POTASSIUM CHANNEL OPENERS DERIVED FROM (+/-)-2-OXO-1-PYRIDIN-3-YL-CYCLOHEXANECARBOTHIOIC ACID METHYLAMIDE - NEW POTASSIUM CHANNEL OPENERS

被引：11

作者：

BROWN, TJ ^{[1
]}

CHAPMAN, RF ^{[1
]}

MASON, JS ^{[1
]}

PALFREYMAN, MN ^{[1
]}

VICKER, N ^{[1
]}

WALSH, RJA ^{[1
]}

机构：

[1] RHONE POULENC RORER LTD,DAGENHAM RES CTR,RAINHAM RD S,DAGENHAM RM10 7XS,ESSEX,ENGLAND

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1993年 / 36卷 / 11期

关键词：

D O I：

10.1021/jm00063a010

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The syntheses and biological activities of (+/-)-2-(cyanomethylene)-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (6) and trans-(+/-)-2-(cyanomethyl)-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (14) derived from (+/-)-2-oxo-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (4) are reported. Compounds were tested for antagonism of potassium-induced contraction of de-endothelialized rat aorta. The effects of modification of 6 and 14 on in vitro K+-channel opening activity are presented. These new series of potassium channel openers so derived are best exemplified by (+/-)-2-[2-(phenylsulfanyl)ethylidene]-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (13d, RP 66266) and trans-(+/-)-2-[2-[(phenylsulfonyl)amino]ethyl]-1-pyridin-3-ylcyclohexanecarbothioic acid methylamide (25a, RP 66784), which have IC90 values of 3 and 0.3 nM, respectively. The potency of the most active compounds indicates a possible interaction at an extra binding site. The compounds described herein are potential antihypertensive and antianginal agents.

引用

页码：1604 / 1612

页数：9

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