Synthesis and optimization of arylsulfonylpiperazines as a novel class of inhibitors of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1)

被引：20

作者：

Sun, Daqing ^{[1
]}

Wang, Zhulun ^{[1
]}

Cardozo, Mario ^{[1
]}

Choi, Rebekah ^{[1
]}

DeGraffenreid, Michael ^{[1
]}

Di, Yongmei ^{[1
]}

He, Xiao ^{[1
]}

Jaen, Juan C. ^{[1
]}

Labelle, Marc ^{[1
]}

Liu, Jinsong ^{[1
]}

Ma, Ji ^{[1
]}

Miao, Shichang ^{[1
]}

Sudom, Athena ^{[1
]}

Tang, Liang ^{[1
]}

Tu, Hua ^{[1
]}

Ursu, Stefania ^{[1
]}

Walker, Nigel ^{[1
]}

Yan, Xuelei ^{[1
]}

Ye, Qiuping ^{[1
]}

Powers, Jay P. ^{[1
]}

机构：

[1] Amgen Inc, San Francisco, CA 94080 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 05期

关键词：

11; beta-HSD1; beta-HSD2; Diabetes; Metabolic syndrome; Hydroxysteroid dehydrogenase; Arylsulfonylpiperazines; SELECTIVE INHIBITORS; METABOLIC SYNDROME; DISCOVERY; POTENT; DRUGS; MICE;

D O I：

10.1016/j.bmcl.2008.12.114

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and SAR of a series of arylsulfonylpiperazine inhibitors of 11 beta-HSD1 are described. Optimization rapidly led to potent, selective, and orally bioavailable inhibitors demonstrating efficacy in a cynomolgus monkey ex vivo enzyme inhibition model. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：1522 / 1527

页数：6

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