Identification of a new biaryl scaffold generating potent renin inhibitors

被引：6

作者：

Lacombe, Patrick ^{[1
]}

Aspiotis, Renee ^{[1
]}

Bayly, Christopher ^{[1
]}

Chen, Austin ^{[1
]}

Dube, Daniel ^{[1
]}

Fortin, Rejean ^{[1
]}

Gallant, Michel ^{[1
]}

Juteau, Helene ^{[1
]}

Liu, Suzanna ^{[1
]}

McKay, Dan ^{[1
]}

Roy, Patrick ^{[1
]}

Wu, Tom ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2010年 / 20卷 / 19期

关键词：

Renin; Inhibitor; Anti-hypertensive; HYPERTENSION; ALISKIREN;

D O I：

10.1016/j.bmcl.2010.07.127

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The discovery and SAR of a series of potent renin inhibitors possessing a novel biaryl scaffold are described herein. Molecular modeling revealed that the cyclopropylamide spacer present in 1 can be replaced by a simple, substituted aromatic ring such as a toluene in 2. The resulting compounds exhibit subnanomolar renin IC(50) and good oral bioavailability in rats. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：5822 / 5826

页数：5

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