3-Thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (S1) Based Molecules as Potent, Dual Inhibitors of B-Cell Lymphoma 2 (Bcl-2) and Myeloid Cell Leukemia Sequence 1 (Mcl-1): Structure-Based Design and Structure-Activity Relationship
发表时间：2019-03-09
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- 论文类型：
- 期刊论文
- 第一作者：
- Zhang, Zhichao
- 通讯作者：
- Zhang, ZC (reprint author), Dalian Univ Technol, Sch Chem, Dalian 116012, Peoples R China.
- 合写作者：
- Wu, Guiye,Xie, Feibo,Song, Ting,Chang, Xilong
- 发表时间：
- 2011-02-24
- 发表刊物：
- JOURNAL OF MEDICINAL CHEMISTRY
- 收录刊物：
- Scopus、SCIE、PubMed
- 文献类型：
- J
- 卷号：
- 54
- 期号：
- 4
- 页面范围：
- 1101-1105
- ISSN号：
- 0022-2623
- 摘要：
- We recently described the discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-1, from which a novel dual inhibitor 3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (6h) was obtained, which showed significant enhanced IC(50) value against Mcl-1 (5 nM), greater Mcl-1/Bak disruption potential, and accordingly a 10-fold increased cytotoxicity over 3.
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- 否
