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Synthesis and Structure−Activity Relationship of a New Series of COX-2 Selective Inhibitors: 1,5-Diarylimidazoles

2003; American Chemical Society; Volume: 46; Issue: 16 Linguagem: Inglês

10.1021/jm030765s

1520-4804

Carmen Almansa, José Alfón, Alberto Fernández de Arriba, Fernando L. Cavalcanti, Ignasi Escamilla, Luis Alberto Gómez, Agustí Miralles, Robert Soliva, Javier Bartrolí, Elena Carceller, Manuel Merlos, Julián Garcı́a-Rafanell,

Synthesis and Reactions of Organic Compounds

The synthesis and the pharmacological activity of a series of 1,5-diarylimidazoles developed as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vivo (carrageenan-induced paw edema, air-pouch, and hyperalgesia tests). Modification of all the positions of two regioisomeric imidazole cores led to the identification of 4-[4-chloro-5-(3-fluoro-4-methoxyphenyl)imidazol-1-yl]benzenesulfonamide (UR-8880, 51f) as the best candidate, which is now undergoing Phase I clinical trials.