Discovery of indazole aldosterone synthase (CYP11B2) inhibitors as potential treatments for hypertension

被引：21

作者：

Hoyt, Scott B. ^{[1
]}

Taylor, Jerry ^{[1
]}

London, Clare ^{[1
]}

Ali, Amjad ^{[1
]}

Ujjainwalla, Feroze ^{[1
]}

Tata, Jim ^{[1
]}

Struthers, Mary ^{[1
]}

Cully, Doris ^{[1
]}

Wisniewski, Tom ^{[1
]}

Ren, Ning ^{[1
]}

Bopp, Charlene ^{[1
]}

Sok, Andrea ^{[1
]}

Verras, Andreas ^{[1
]}

McMasters, Daniel ^{[1
]}

Chen, Qing ^{[1
]}

Tung, Elaine ^{[1
]}

Tang, Wei ^{[1
]}

Salituro, Gino ^{[1
]}

Clemas, Joe ^{[1
]}

Zhou, Gaochao ^{[1
]}

MacNeil, Douglas ^{[1
]}

Duffy, Ruth ^{[1
]}

Xiong, Yusheng ^{[1
]}

机构：

[1] Merck Res Labs, POB 2000, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2017年 / 27卷 / 11期

关键词：

Aldosterone synthase; CYP11B2; Indazole; Hit-to-lead; Hypertension; IN-VIVO ACTIVITY; PYRIDYL;

D O I：

10.1016/j.bmcl.2017.04.021

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We report the discovery and hit-to-lead optimization of a structurally novel indazole series of CYP11B2 inhibitors. Benchmark compound 34 from this series displays potent inhibition of CYP11B2, high selectivity versus related steroidal and hepatic CYP targets, and lead-like physical and pharmacokinetic properties. On the basis of these and other data, the indazole series was progressed to lead optimization for further refinement. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：2384 / 2388

页数：5

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