title: Design, synthesis and biological evaluation of novel imidazo[4,5-c]pyridinecarboxamide derivatives as PARP-1 inhibitors.
abstract: A series of novel cyclic amine-substituted imidazo[4,5-c]pyridinecarboxamide analogs were designed and synthesized. All the target compounds were evaluated for their PARP inhibition activity, and the result indicated that most of the compounds possessed inhibitory effect on PARP at the concentration of 1μM, among which compound 8d (IC50=0.528 μM) was selected for evaluating the antitumor effect in vivo. The result showed the antitumor efficacy of the compound 8d and cisplatin combination group in a mouse A549 model is similar with that of the ABT-888 and cisplatin combination group.
authors.affiliation: Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Zhu
authors.forename: Xuyan
authors.initials: X
authors.lastname: Wang
authors.forename: Zhaoxing
authors.initials: Z
authors.lastname: Chu
authors.forename: Guangwei
authors.initials: G
authors.lastname: He
authors.forename: Guangping
authors.initials: G
authors.lastname: Dong
authors.forename: Yungen
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D004791:Enzyme Inhibitors; D007093:Imidazoles; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009536:Niacinamide; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases