title: Design of novel N-phenylnicotinamides as selective cyclooxygenase-1 inhibitors.
abstract: A series of N-phenylnicotinamides (1-40) were designed and evaluated in vitro for their COX inhibitory activities. Most of the synthesized compounds were proved to be potent and selective inhibitors of COX-1. Compound 28 showed the most potent COX-1 inhibitory activity (COX-1 IC(50) = 0.68 ± 0.07 μM) and good selectivity (COX-2 IC(50)>100μM). This compound may be useful as a lead compound for superior COX-1 inhibitors. On the basis of the biological results, structure-activity relationships for the COX-1-inhibitory activities of the synthesized N-phenylnicotinamides were discussed concisely.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.forename: Zi-Lin
authors.initials: ZL
authors.lastname: Li
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhen-Wei
authors.initials: ZW
authors.lastname: Zhu
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000813:Anilides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D003198:Computer Simulation; D051545:Cyclooxygenase 1 / Q000737:chemistry* / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000813:Anilides; D016861:Cyclooxygenase Inhibitors; D009536:Niacinamide; D051545:Cyclooxygenase 1