Structure-Activity Relationship Study of a Series of Caspase Inhibitors Containing γ-Amino Acid Moiety for Treatment of Cholestatic Liver Disease

Jianfeng Mou, Songliang Wu, Zhi Luo, Fengying Guo, Haiying He, Jianhua Wang, Fusen Lin, Fengxun Guo, Jianping Sun, Liang Shen, Minggao Zeng, Chuan Wang, Deming Xu, Zhengxian Gu, Xin Tian, Aiming Zhang, Hongjiang Xu, Ling Yang, Xiquan Zhang, Jian Li, Shuhui Chen

Index: 10.1016/j.bmcl.2018.04.002

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Abstract

A series of caspase inhibitors containing γ-amino acid moiety have been synthesized. A systemic study on their structure-activity relationship of anti-apoptotic cellular activity is presented. These efforts led to the discovery of compound 20o as a potent caspase inhibitor, which demonstrated preclinical ameliorating total bilirubin efficacy with a significantly improved pharmacokinetic profile.