Synthesis and optimization of novel 4, 4-disubstituted cyclohexylbenzamide derivatives as potent 11β-HSD1 inhibitors

D Sun, Z Wang, S Caille, M DeGraffenreid…

Index: Sun, Daqing; Wang, Zhulun; Caille, Seb; Degraffenreid, Michael; Gonzalez-Lopez De Turiso, Felix; Hungate, Randall; Jaen, Juan C.; Jiang, Ben; Julian, Lisa D.; Kelly, Ron; McMinn, Dustin L.; Kaizerman, Jacob; Rew, Yosup; Sudom, Athena; Tu, Hua; Ursu, Stefania; Walker, Nigel; Willcockson, Maren; Yan, Xuelei; Ye, Qiuping; Powers, Jay P. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 1 p. 405 - 410

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Citation Number: 13

Abstract

The synthesis and SAR of a series of 4, 4-disubstituted cyclohexylbenzamide inhibitors of 11β-HSD1 are described. Optimization rapidly led to potent, highly selective, and orally bioavailable inhibitors demonstrating efficacy in both rat and non-human primate ex vivo pharmacodynamic models.