title: Synthesis of 1,5-diarylhaloimidazole analogs and their inhibitory activities against PGE₂ production from LPS-treated RAW 264.7 cells.
abstract: A number of 1,5-diarylimidazole analogs were synthesized and evaluated their inhibitory activities of cyclooxygenase-2 catalyzed prostaglandin E(2) production. Reactions of 1,5-diarylimidazoles with halogenating reagents (NCS, NBS, NIS) afforded halogenated analogs. Among the analogs tested, compounds Ib, IIa, IIb and IIe exhibited significantly improved inhibitory activities against COX-2-mediated PGE(2) production from LPS-induced RAW 264.7 cells compared to those of the parent 1,5-diarylimidazoles. Especially, the analogs Ib (IC(50)=0.55 μM) and IIa (IC(50)=0.58 μM) showed best results. Halogenation on the 1,5-diarylimidazole ring enhanced inhibitory activities against COX-2 catalyzed PGE(2) production, however, inhibitory activities were significantly varied by position(s) and species of the substituted halogen(s).
authors.affiliation: College of Pharmacy, Chuncheon 200-701, Republic of Korea.
authors.forename: Zunhua
authors.initials: Z
authors.lastname: Yang
authors.forename: Tuyen N
authors.initials: TN
authors.lastname: Truong
authors.forename: Tuan-Anh N
authors.initials: TA
authors.lastname: Pham
authors.forename: Jae-Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Sung-Soo
authors.initials: SS
authors.lastname: Kim
authors.forename: Haeil
authors.initials: H
authors.lastname: Park
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000032:analysis / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D007093:Imidazoles; D008070:Lipopolysaccharides; D015232:Dinoprostone