Preparation and optimization of a series of 3-carboxamido-5-phenacylaminopyrazole bradykinin B1 receptor antagonists

被引：38

作者：

Dressen, Darren ^{[1
]}

Garofalo, Albert W. ^{[1
]}

Hawkinson, Jon ^{[1
]}

Hom, Dennis ^{[1
]}

Jagodzinski, Jacek ^{[1
]}

Marugg, Jennifer L. ^{[1
]}

Neitzel, Martin L. ^{[1
]}

Pleiss, Michael A. ^{[1
]}

Szoke, Balazs ^{[1
]}

Tung, Jay S. ^{[1
]}

Wone, David W. G. ^{[1
]}

Wu, Jing ^{[1
]}

Zhang, Heather ^{[1
]}

机构：

[1] Elan Pharmaceut Inc, San Francisco, CA 94080 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 21期

关键词：

D O I：

10.1021/jm051292n

中图分类号：

R914 [药物化学];

学科分类号：

100701 [药物化学];

摘要：

The B1 receptor is an attractive target for the treatment of pain and inflammation. A series of 3-carboxamido5-phenacylamino pyrazole B1 receptor antagonists are described that exhibit good potency against B1 and high selectivity over B2. Initially, N-unsubstituted pyrazoles were studied, but these compounds suffered from extensive glucuronidation in primates. This difficulty could be surmounted by the use of N-substituted pyrazoles. Optimization efforts culminated in compound 41, which has high receptor potency and metabolic stability.

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页码：5161 / 5167

页数：7

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