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. Issue 20 (15th October 2015)

• Record Type: Journal Article
• Authors: Zhu, Qihua; Wang, Xueyan; Hu, Yan; He, Xiaorong; Gong, Guoqing; Xu, Yungen
• Is Part Of: Bioorganic & medicinal chemistry. Volume 23:Issue 20(2015)
• Page Start: 6551
• Page End: 6559
• Publication Date: 2015-10-15
• Subjects: Imidazo[4, 5-c]pyridine-7-carboxamide -- PARP inhibitor -- Antitumor; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2015.09.026
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: A series of novel 2-(piperidin-4-yl)-3 H -imidazo[4, 5- c ]pyridine-7-carboxamide derivatives as PARP inhibitors is described. Abstract: 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)-3 H -imidazo[4, 5- c ]pyridine-7-carboxamide11a (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.