Discovery and SAR study of 2-(1-propylpiperidin-4-yl)-3H-imidazo [4,5-c]pyridine-7-carboxamide: A potent inhibitor of poly(ADP-ribose) polymerase-1 (PARP-1) for the treatment of cancer

被引：15

作者：

Zhu, Qihua ^{[1
,2
]}

Wang, Xueyan ^{[1
]}

Hu, Yan ^{[2
]}

He, Xiaorong ^{[3
]}

Gong, Guoqing ^{[1
]}

Xu, Yungen ^{[1
,2
]}

机构：

[1] China Pharmaceut Univ, Jiangsu Key Lab Drug Design & Optimizat, Nanjing 21009, Jiangsu, Peoples R China

[2] China Pharmaceut Univ, Dept Med Chem, Nanjing 21009, Jiangsu, Peoples R China

[3] China Pharmaceut Univ, Sch Engn, Nanjing 21009, Jiangsu, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 20期

关键词：

Imidazo[4,5-c]pyridine-7-carboxamide; PARP inhibitor; Antitumor; DNA-REPAIR; PHASE-I; TEMOZOLOMIDE; DERIVATIVES; OLAPARIB; ABT-888; AZD2281; MODELS; GROWTH; DOMAIN;

D O I：

10.1016/j.bmc.2015.09.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

A series of imidazo[4,5-c]pyridine-7-carboxamide derivatives as poly(ADP-ribose) polymerase (PARP) inhibitors have been developed. All target compounds were evaluated for their PARP-1 inhibitory activity and some were further assessed for cellular potency. These efforts led to identification of a novel PARP-1 inhibitor 2-(1-propylpiperidin-4-yl)-3H-imidazo[4,5-c]pyridine-7-carboxamide 11a (XZ-120312). 11a displayed strong inhibition against the PARP-1 enzyme with an IC50 of 8.6 +/- 0.6 nM and excellent potentiation of temozolomide cytotoxicity in cancer cell lines SW-620, MDA-MB-468 and A549 by 4.0, 3.0 and 7.7 times, respectively. (c) 2015 Elsevier Ltd. All rights reserved.

引用

页码：6551 / 6559

页数：9

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