EVOLUTION OF A SERIES OF PEPTIDOLEUKOTRIENE ANTAGONISTS - SYNTHESIS AND STRUCTURE-ACTIVITY-RELATIONSHIPS OF 1,6-DISUBSTITUTED INDOLES AND INDAZOLES

被引：38

作者：

BROWN, FJ ^{[1
]}

YEE, YK ^{[1
]}

CRONK, LA ^{[1
]}

HEBBEL, KC ^{[1
]}

KRELL, RD ^{[1
]}

SNYDER, DW ^{[1
]}

机构：

[1] ICI AMER INC, BUSINESS UNIT, ICI PHARMACOL GRP, DEPT PHARMACOL, WILMINGTON, DE 19897 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 06期

关键词：

D O I：

10.1021/jm00168a036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A perception of structural similarities between two independent series of leukotriene antagonists (one emanating from FPL 55712 and one based upon the leukotrienes themselves) led to the discovery of a novel class of indole and indazole derived antagonists of peptidoleukotrienes. A systematic exploration of C-6 substituted 4-(indol-l-ylmethyl)-3-methoxybenzoic acids identified cyclopentylacetamide and cyclopentylurethane as preferred substituents. The corresponding indazoles were equipotent. These compounds are selective leukotriene antagonists with pKB values of 7.5-7.8 vs LTE4 on guinea pig trachea. © 1990, American Chemical Society. All rights reserved.

引用

页码：1771 / 1781

页数：11

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