Discovery and optimization of piperidyl benzamide derivatives as a novel class of 11β-HSD1 inhibitors

Y Rew, DL McMinn, Z Wang, X He, RW Hungate…

Index: Rew, Yosup; McMinn, Dustin L.; Wang, Zhulun; He, Xiao; Hungate, Randall W.; Jaen, Juan C.; Sudom, Athena; Sun, Daqing; Tu, Hua; Ursu, Stefania; Villemure, Elisia; Walker, Nigel P.C.; Yan, Xuelei; Ye, Qiuping; Powers, Jay P. Bioorganic and Medicinal Chemistry Letters, 2009 , vol. 19, # 6 p. 1797 - 1801

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Citation Number: 27

Abstract

Discovery and optimization of a piperidyl benzamide series of 11β-HSD1 inhibitors is described. This series was derived from a cyclohexyl benzamide lead structures to address PXR selectivity, high non-specific protein binding, poor solubility, limited in vivo exposure, and in vitro cytotoxicity issues observed with the cyclohexyl benzamide structures. These efforts led to the discovery of piperidyl benzamide 15 which features improved properties ...