2-(S)-phenethylaminothiazolones as potent, orally efficacious inhibitors of 11β-hydroxysteriod dehydrogenase type 1

被引：20

作者：

Jean, David J. St., Jr. ^{[1
]}

Yuan, Chester

Bercot, Eric A.

Cupples, Rod

Chen, Michelle

Fretland, Jenne

Hale, Clarence

Hungate, Randall W.

Komorowski, Renee

Veniant, Murielle

Wang, Minghan

Zhang, Xiping

Fotsch, Christopher

机构：

[1] Amgen Inc, Dept Med Chem, Thousand Oaks, CA 91320 USA

[2] Amgen Inc, Dept Small Mol Proc Dev, Thousand Oaks, CA 91320 USA

[3] Amgen Inc, Dept Metab Disorders, Thousand Oaks, CA 91320 USA

[4] Amgen Inc, Dept Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 03期

关键词：

D O I：

10.1021/jm061214f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

11 beta-hydroxysteroid dehydrogenase type 1 (11 beta-HSD1) is the enzyme that converts cortisone to cortisol. A growing body of evidence suggests that selective inhibition of 11 beta-HSD1 could potentially treat metabolic syndrome as well as type 2 diabetes. Through modification of our initial lead 1, we have discovered trifluoromethyl thiazolone 17. This compound had a K-i of 22 nM, possessed low in vivo clearance, and showed a 91% inhibition of adipose 11 beta-HSD1 enzymatic activity in a mouse ex vivo pharmacodynamic model.

引用

页码：429 / 432

页数：4

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