Design and Synthesis of (R)-1-Arylsulfonylpiperidine-2-carboxamides as 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors

被引：6
作者：
Xia, Guangxin [1 ,2 ]
Liu, Lin [1 ,2 ]
Liu, Haiyan [1 ]
Yu, Jianxin [1 ]
Xu, Zhenmin [1 ]
Chen, Qian [1 ]
Ma, Chen [1 ]
Li, Ping [1 ]
Xiong, Bing [2 ]
Liu, Xuejun [1 ]
Shen, Jingkang [1 ,2 ]
机构：
[1] Shanghai Pharmaceut Holding Co Ltd, Cent Res Inst, Shanghai 201203, Peoples R China
[2] Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
来源：
CHEMMEDCHEM | 2013年 / 8卷 / 04期
关键词：
11-HSD1; diabetes; docking; inhibitors; 11-BETA-HSD1; INHIBITORS; SELECTIVE INHIBITORS; DISCOVERY; DOCKING; POTENT;
D O I：
10.1002/cmdc.201300022
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
R adamantly beats S: 11β-HSD1 is a target for treating metabolic syndrome. The Risomer 5 was selected as a starting point for optimization and SAR studies. Inhibitor 8w emerged after several rounds of optimization, showing cross-species inhibition of human and mouse 11β-HSD1. It also displays a good DMPK profile invitro, and was advanced to PK/PD evaluations invivo. The results confirmed its dose-dependent activity in mice. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
引用
收藏
页码：577 / 581
页数：5
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