3-Thiomorpholin-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-carbonitrile (S1) derivatives as pan-Bcl-2-inhibitors of Bcl-2, Bcl-x L and Mcl-1

…, X Chang, X Liang, Y Zhao, G Wu, S Xie, P Su…

Index: Song, Ting; Li, Xiangqian; Chang, Xilong; Liang, Xiaomeng; Zhao, Yan; Wu, Guiye; Xie, Shenghui; Su, Pengchen; Wu, Zhiyong; Feng, Yingang; Zhang, Zhichao Bioorganic and Medicinal Chemistry, 2013 , vol. 21, # 1 p. 11 - 20

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Citation Number: 21

Abstract

Based on the binding mode of our previously discovered dual inhibitor of Bcl-2 and Mcl-1, 3- thiomorpholin-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-carbonitrile (3, S1), a library of 9- substituted 3 derivatives was synthesized to further probe the p4 pocket of the two targets. By NMR, structure–activity relationship study, and site-directed mutation, compound 6d (3-(4- aminophenylthio)-8-oxo-8H-acenaphtho [1, 2-b] pyrrole-9-3-phenyl) propylamine) was ...