Pyrrolidine-3-carboxylic acids as endothelin antagonists.: 5.: Highly selective, potent, and orally active ETA antagonists

被引：34

作者：

Jae, HS ^{[1
]}

Winn, M ^{[1
]}

von Geldern, TW ^{[1
]}

Sorensen, BK ^{[1
]}

Chiou, WJ ^{[1
]}

Nguyen, B ^{[1
]}

Marsh, KC ^{[1
]}

Opgenorth, TJ ^{[1
]}

机构：

[1] Abbott Labs, Metab Dis Res & Drug Anal Dept, Pharmaceut Prod Res Div, Abbott Pk, IL 60064 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 23期

关键词：

D O I：

10.1021/jm010237l

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and structure-activity relationships (SAR) of a series of pyrrolidine-3-carboxylic acids as endothelin antagonists are described. The data shows an increase in selectivity when the methoxy of Atrasentan (ABT-627) is replaced with methyl, and the benzodioxole is replaced with dihydrobenzofuran. Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ETA-selective antagonist.

引用

页码：3978 / 3984

页数：7

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