Adamantane 11-β-HSD-1 inhibitors:: Application of an isocyanide multicomponent reaction

被引：36

作者：

Sorensen, Bryan

Rohde, Jeff

Wang, Jiahong

Fung, Steven

Monzon, Katina

Chiou, William

Pan, Liping

Deng, Xiaoqing

Stolarik, DeAnne

Frevert, Ernst U.

Jacobson, Peer

Link, J. T.

机构：

[1] Abbott Labs, Metab Dis Res, Abbott Pk, IL 60064 USA

[2] Abbott Labs, Drug Metab, Abbott Pk, IL 60064 USA

[3] Abbott Labs, Exploratory Sci, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 23期

关键词：

11-beta-HSD-1; inhibitors; adamantane; multicomponent reaction; metabolism; HSD1; inhibitor; hydroxysteroid dehydrogenase type 1; metabolic syndrome;

D O I：

10.1016/j.bmcl.2006.08.129

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of potent and selective adamantane aminoamide 1-beta-HSD-1 inhibitors has been optimized. Chemically these studies were expedited by utilizing readily obtained amino acids as starting materials or an isocyanide multicomponent reaction. Structure-activity relationship studies resulted in the discovery of dual human and mouse 11-beta-HSD-1 potent and selective inhibitors like adamantane 11 and related compounds with high metabolic stability and robust pharmacokinetic profiles. (c) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：5958 / 5962

页数：5

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