Citation: Zhang Xinwei, Zhang Cunlong, Tang Lin, Lu Kuan, Zhao Huan, Wu Weibin, Jiang Yuyang. Synthesis and biological evaluation of piperidyl benzimidazole carboxamide derivatives as potent PARP-1 inhibitors and antitumor agents[J]. Chinese Chemical Letters, ;2020, 31(1): 136-140. doi: 10.1016/j.cclet.2019.04.045 shu

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

Zhang Xinwei ^a,b,1 ,
Zhang Cunlong ^c,1 ,
Tang Lin ^c ,
Lu Kuan ^c ,
Zhao Huan ^d ,
Wu Weibin ^c,**, ,
Jiang Yuyang ^b,e,**,

a.
Department of Chemistry, Tsinghua University, Beijing 100084, China
b.
The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China
c.
Shenzhen Kivita Innovative Drug Discovery Institute, Shenzhen 518057, China
d.
Shenzhen Ruikang Pharmaceutical Technology Co., Ltd., Shenzhen 518057, China
e.
Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China

^**

Received Date: 12 March 2019
Revised Date: 15 April 2019
Accepted Date: 17 April 2019
Available Online: 18 January 2019

Figures(3)

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.
- PARP-1 inhibitor,
- Piperidyl benzimidazole carboxamide,
- A-620223,
- Structure-activity relationship,
- Antitumor activity
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