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

作者：Zhu, Qihua; Wang, Xueyan; Hu, Yan; He, Xiaorong; Gong, Guoqing; Xu, Yungen^*

来源：Bioorganic & Medicinal Chemistry, 2015, 23(20): 6551-6559.

DOI：10.1016/j.bmc.2015.09.026

• Imidazo[4,5-c]pyridine-7-carboxamide
• PARP inhibitor
• Antitumor

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.

• 出版日期2015-10-15
• 单位中国药科大学