Synthesis and biological evaluation of piperidyl benzimidazole carboxamide derivatives as potent PARP-1 inhibitors and antitumor agents

被引：19

作者：

Zhang, Xinwei ^{[1
,2
]}

Zhang, Cunlong ^{[3
]}

Tang, Lin ^{[3
]}

Lu, Kuan ^{[3
]}

Zhao, Huan ^{[4
]}

Wu, Weibin ^{[3
]}

Jiang, Yuyang ^{[2
,5
]}

机构：

[1] Tsinghua Univ, Dept Chem, Beijing 100084, Peoples R China

[2] Tsinghua Univ, State Key Lab Chem Oncogen, Key Lab Chem Biol, Grad Sch Shenzhen, Shenzhen 518055, Peoples R China

[3] Shenzhen Kivita Innovat Drug Discovery Inst, Shenzhen 518057, Peoples R China

[4] Shenzhen Ruikang Pharmaceut Technol Co Ltd, Shenzhen 518057, Peoples R China

[5] Tsinghua Univ, Sch Med, Dept Pharmacol & Pharmaceut Sci, Beijing 100084, Peoples R China

来源：

CHINESE CHEMICAL LETTERS | 2020年 / 31卷 / 01期

关键词：

PARP-1; inhibitor; Piperidyl benzimidazole carboxamide; A-620223; Structure-activity relationship; Antitumor activity; POLY(ADP-RIBOSE) POLYMERASE PARP; REFRACTORY SOLID TUMORS; PHASE-I; ABT-888; COMBINATION; DISCOVERY; DESIGN; ADULTS;

D O I：

10.1016/j.cclet.2019.04.045

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

We have synthesized a series of compounds based on a piperidyl benzimidazole carboxamide structure, and tested their PARP-1 inhibitory activity, as well as cellular inhibitory activity. Some of them show great potency as PARP-1 inhibitors and antitumor activity, which are valuable for further research. In addition, the predicted ADME properties and proposed binding mode with PARP-1 of the compounds were obtained via computational simulation. (C) 2019 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.

引用

页码：136 / 140

页数：5

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