Design, synthesis and biological evaluation of novel 5-fluoro-1H-benzimidazole-4-carboxamide derivatives as potent PARP-1 inhibitors

被引：19

作者：

Wang, Junwei ^{[1
,2
]}

Wang, Xuyan ^{[2
]}

Li, Hui ^{[1
]}

Ji, Dezhong ^{[1
]}

Li, Yuyan ^{[2
]}

Xu, Yungen ^{[1
,2
]}

Zhu, Qihua ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 210009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Dept Med Chem, Nanjing 210009, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 16期

基金：

中国国家自然科学基金;

关键词：

PARP-1; Inhibitors; Fluorine atom; Benzimidazole; Antitumor; MEDICINAL CHEMISTRY; CANCER; OVARIAN; VELIPARIB; FLUORINE; BRCANESS;

D O I：

10.1016/j.bmcl.2016.06.045

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of novel 5-fluorine-benzimidazole-4-carboxamide analogs were designed and synthesized. All target compounds were evaluated for their PARP-1 inhibitory activity. Compounds possessed high intrinsic PARP-1 inhibitory potency have been evaluated in vitro cellular assays to measure the potentiation effect of cytotoxic agents against cancer cell line. These efforts led to the identification of compound 10f, which displayed strong inhibition against the PARP-1 enzyme with an IC50 of 43.7 nM, excellent cell inhibitory activity in HCT116 cells (IC50 = 7.4 mu M) and potentiation of temozolomide cytotoxicity in cancer cell line A549 (PF50 = 1.6). (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：4127 / 4132

页数：6

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