Discovery of 4-heteroarylbicyclo[2.2.2]octyltriazoles as potent and selective inhibitors of 11β-HSD1:: Novel therapeutic agents for the treatment of metabolic syndrome

被引：54

作者：

Gu, X

Dragovic, J

Koo, GC

Koprak, SL

LeGrand, C

Mundt, SS

Shah, K

Springer, MS

Tan, EY

Thieringer, R

Hermanowski-Vosatka, A

Zokian, HJ

Balkovec, JM

Waddell, ST

机构：

[1] Merck & Co Inc, Dept Med Chem, Rahway, NJ 07065 USA

[2] Merck & Co Inc, Dept Cardiovasc Dis, Rahway, NJ 07065 USA

[3] Merck & Co Inc, Dept Drug Metab, Rahway, NJ 07065 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 23期

关键词：

metabolic syndrome; 11 beta-hydroxysteroid dehydrogenase type I; 11; beta-HSD1; beta-HSD2; glucocorticoids; cortisone; cortisol; bicyclo[2.2.2]octyltriazole; heterocycle; oxadiazole; imidazole; triazole; pharmacokinectics; pharmacodynamic assay;

D O I：

10.1016/j.bmcl.2005.08.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Replacement of the pentyl chain on our original bicyclo[2.2.2]octyltriazole leads 1 and 2 has led to the discovery that heteroaryl substituted bicyclo[2.2.2]octyltriazoles are potent and selective 11 beta-hydroxysteroid dehydrogenase type I (11 beta-HSD1) inhibitors with excellent pharmacokinetic profiles. (c) 2005 Elsevier Ltd. All rights reserved.

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页码：5266 / 5269

页数：4

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