A novel class of small-molecule caspase-3 inhibitors prepared by multicomponent reactions

被引：56

作者：

Zhu, Qiuhua ^{[1
,2
]}

Gao, Lixin ^{[3
]}

Chen, Zhipeng ^{[1
]}

Zheng, Sichao ^{[1
]}

Shu, Huafei ^{[1
]}

Li, Jia ^{[3
]}

Jiang, Huanfeng ^{[2
]}

Liu, Shuwen ^{[1
]}

机构：

[1] So Med Univ, Sch Pharmaceut Sci, Guangzhou 510515, Guangdong, Peoples R China

[2] S China Univ Technol, Sch Chem & Chem Engn, Guangzhou 510640, Peoples R China

[3] Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Chinese Natl Ctr Drug Screening, Shanghai 201203, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 54卷

关键词：

Caspase-3; inhibitor; Dihydropyrrole; Multicomponent reaction; Synthesis; PARTITION-COEFFICIENTS; SULFONAMIDE ANALOGS; DRUG DISCOVERY; CELL-DEATH; APOPTOSIS; POTENT; TETRAHYDROPYRIMIDINES; SOLUBILITY; MECHANISMS; CANCER;

D O I：

10.1016/j.ejmech.2012.05.001

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of tetra- and pentasubstituted polyfunctional dihydropyrroles 5 and 6 were synthesized via practical multicomponent reactions (MCRs) for research on their structure activity relationship as caspase-3 inhibitors. Among 39 compounds evaluated, 14 of them exhibited inhibition against caspase-3 with IC50 ranging from 5 to 20 mu M. The inhibitory activities of 5 and 6 depend on the nature of substituents on different positions. 5 and 6 possess a different scaffold from those previously reported and are the first caspase-3 inhibitors prepared via MCRs. The most active compounds 5k (IC50 = 5.27 mu M) could therefore be used as a lead for the development of highly potent caspase-3 inhibitors as drug candidates for therapeutic agents by taking advantage of MCRs. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：232 / 238

页数：7

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