Discovery of adamantane ethers as inhibitors of 11β-HSD-1:: Synthesis and biological evaluation

被引：41

作者：

Patel, Jyoti R. ^{[1
]}

Shuai, Qi ^{[1
]}

Dinges, Jurgen ^{[1
]}

Winn, Marty ^{[1
]}

Pliushchev, Marina ^{[1
]}

Fung, Steven ^{[1
]}

Monzon, Katina ^{[1
]}

Chiou, William ^{[1
]}

Wang, Jiahong ^{[1
]}

Pan, Liping ^{[1
]}

Wagaw, Seble ^{[1
]}

Engstrom, Kenneth ^{[1
]}

Kerdesky, Francis A. ^{[1
]}

Longenecker, Kenton ^{[1
]}

Judge, Russell ^{[1
]}

Qin, Wenying ^{[1
]}

Imade, Hovis M. ^{[1
]}

Stolarik, DeAnne ^{[1
]}

Beno, David W. A. ^{[1
]}

Brune, Michael ^{[1
]}

Chovan, Linda E. ^{[1
]}

Sham, Hing L. ^{[1
]}

Jacobson, Peer ^{[1
]}

Link, J. T. ^{[1
]}

机构：

[1] Abbott Labs, Global Pharmaceut Res & Dev, Abbott Pk, IL 60064 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 03期

关键词：

metabolic syndrome; 11; beta-HSD-1; beta-HSD-2; inhibitor; adamantane ethers; X-ray crystal structure;

D O I：

10.1016/j.bmcl.2006.10.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A novel class of adamantane ethers 11 beta-hydroxysteroid hydrogenase type I inhibitors has been discovered. These compounds have excellent HSD-1 potency and selectivity against HSD-2. The structure-activity relationships, selectivity, metabolism, PK, ex vivo pharmacodynarnic data, and an X-ray crystal structure of one of these inhibitors bound to h-HSD-1 are discussed. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：750 / 755

页数：6

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