Synthesis and structure-activity relationship of a new series of COX-2 selective inhibitors: 1,5-diarylimidazoles.

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Almansa C, Alfon J, de Arriba AF, Cavalcanti FL, Escamilla I, Gomez LA, Miralles A, Soliva R, Bartroli J, Carceller E, Merlos M, Garcia-Rafanell J

Synthesis and structure-activity relationship of a new series of COX-2 selective inhibitors: 1,5-diarylimidazoles.

J Med Chem. 2003 Jul 31;46(16):3463-75.

PubMed ID
12877584 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)600N/AN/ADetails
CelecoxibProstaglandin G/H synthase 2IC 50 (nM)79N/AN/ADetails
CimicoxibProstaglandin G/H synthase 2IC 50 (nM)5N/AN/ADetails
CimicoxibProstaglandin G/H synthase 2IC 50 (nM)66N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2IC 50 (nM)9N/AN/ADetails
IndomethacinProstaglandin G/H synthase 2IC 50 (nM)640N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)280N/AN/ADetails
RofecoxibProstaglandin G/H synthase 2IC 50 (nM)12N/AN/ADetails