- Design and synthesis of (R)-1-arylsulfonylpiperidine-2-carboxamides as 11β-hydroxysteroid dehydrogenase type 1 inhibitors.
Design and synthesis of (R)-1-arylsulfonylpiperidine-2-carboxamides as 11β-hydroxysteroid dehydrogenase type 1 inhibitors.
ChemMedChem (2013-03-09)
Guangxin Xia, Lin Liu, Haiyan Liu, Jianxin Yu, Zhenmin Xu, Qian Chen, Chen Ma, Ping Li, Bing Xiong, Xuejun Liu, Jingkang Shen
PMID23471829
ABSTRACT
R adamantly beats S: 11β-HSD1 is a target for treating metabolic syndrome. The R isomer 5 was selected as a starting point for optimization and SAR studies. Inhibitor 8 w 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.