Design and Synthesis of (R)‐1‐Arylsulfonylpiperidine‐2‐carboxamides as 11β‐Hydroxysteroid Dehydrogenase Type 1 Inhibitors. Issue 4 (7th March 2013)

• Record Type: Journal Article
• Authors: Xia, Guangxin; Liu, Lin; Liu, Haiyan; Yu, Jianxin; Xu, Zhenmin; Chen, Qian; Ma, Chen; Li, Ping; Xiong, Bing; Liu, Xuejun; Shen, Jingkang
• Is Part Of: ChemMedChem. Volume 8:Issue 4(2013:Apr.)
• Page Start: 577
• Page End: 581
• Publication Date: 2013-03-07
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201300022
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="graphical" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p> <italic> <bold>R</bold> </italic> <bold>adamantly beats</bold> <italic> <bold>S</bold> </italic> <bold>:</bold> 11β‐HSD1 is a target for treating metabolic syndrome. The <italic>R</italic> isomer <bold>5</bold> was selected as a starting point for optimization and SAR studies. Inhibitor <bold>8 w</bold> emerged after several rounds of optimization, showing cross‐species inhibition of human and mouse 11β‐HSD1. It also displays a good DMPK profile in vitro, and was advanced to PK/PD evaluations in vivo. The results confirmed its dose‐dependent activity in mice.<boxed-text content-type="graphic" position="anchor" orientation="portrait"><graphic position="anchor" mimetype="image" xlink:href="ark:/27927/pgg1x53ndfj" orientation="portrait" xlink:type="simple" xmlns:xlink="http://www.w3.org/1999/xlink" /></boxed-text></p> </abstract>