Small Molecule 11β- Hydroxysteroid Dehydrogenase Type 1 Inhibitors

被引：21

作者：

Sun, Daqing ^{[1
]}

Wang, Minghan ^{[2
]}

Wang, Zhulun ^{[1
]}

机构：

[1] Amgen Inc, 1120 Vet Blvd, San Francisco, CA 94080 USA

[2] Amgen Inc, Thousand Oaks, CA 91320 USA

来源：

CURRENT TOPICS IN MEDICINAL CHEMISTRY | 2011年 / 11卷 / 12期

关键词：

11; beta-HSD1; beta-HSD2; metabolic syndrome; type; 2; diabetes; sulfonamide; amide; triazole; BETA-KETO SULFONES; SELECTIVE INHIBITORS; ADIPOSE-TISSUE; 11-BETA-HYDROXYSTEROID DEHYDROGENASES; GLUCOCORTICOID ACTION; METABOLIC SYNDROME; VISCERAL OBESITY; DISCOVERY; POTENT; TRIAZOLES;

D O I：

10.2174/156802611795860988

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) catalyzes the interconversion of inactive cortisone to active cortisol in a NADPH dependent manner. Excess cortisol or 11 beta-HSD1 leads to insulin resistance and metabolic syndrome. Inhibition of 11 beta-HSD1 activity has been pursued vigorously by the pharmaceutical industry as a potential therapeutic strategy for the treatment of type 2 diabetes. As a result, a large number of chemical classes have been identified as potent and selective small molecule inhibitors for 11 beta-HSD1. Here we review the recent progress in the discovery and development of small molecule inhibitors of 11 beta-HSD1 by highlighting the medicinal chemistry, SAR, in vivo pharmacodynamic effects and efficacy of a few representative classes of inhibitors in models of diabetes. Furthermore, we also review the structural characteristics of each class of inhibitors by analyzing the inhibitor co-crystal structures of 11 beta-HSD1.

引用

页码：1464 / 1475

页数：12

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