Discovery of a Potent, Selective, and Orally Bioavailable Acidic 11尾-Hydroxysteroid Dehydrogenase Type 1 (11尾-HSD1) Inhibitor: Discovery of 2-[(3S)-1-[5-(Cyclohexylcarbamoyl)-6-propylsulfanylpy

详细信息    查看全文

• 作者：James S. Scott ; Suzanne S. Bowker ; Joanne deSchoolmeester ; Stefan Gerhardt ; David Hargreaves ; Elaine Kilgour ; Adele Lloyd ; Rachel M. Mayers ; William McCoull ; Nicholas J. Newcombe ; Derek Ogg ; Martin J. Packer ; Amanda Rees ; John Revill ; Paul Schofield ; Nidhal Selmi ; John G. Swales ; Paul R. O. Whittamore
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：June 28, 2012
• 年：2012
• 卷：55
• 期：12
• 页码：5951-5964
• 全文大小：494K
• 年卷期：v.55,no.12(June 28, 2012)
• ISSN：1520-4804

文摘

Inhibition of 11尾-HSD1 is an attractive mechanism for the treatment of obesity and other elements of the metabolic syndrome. We report here the discovery of a nicotinic amide derived carboxylic acid class of inhibitors that has good potency, selectivity, and pharmacokinetic characteristics. Compound 11i (AZD4017) is an effective inhibitor of 11尾-HSD1 in human adipocytes and exhibits good druglike properties and as a consequence was selected for clinical development.