Synthesis and SAR of a new series of COX-2-selective inhibitors: pyrazolo[1,5-a]pyrimidines.

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Almansa C, de Arriba AF, Cavalcanti FL, Gomez LA, Miralles A, Merlos M, Garcia-Rafanell J, Forn J

Synthesis and SAR of a new series of COX-2-selective inhibitors: pyrazolo[1,5-a]pyrimidines.

J Med Chem. 2001 Feb 1;44(3):350-61.

PubMed ID

11462976 [ View in PubMed

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Abstract

The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-a]pyrimidines 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 and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidi ne (10f) as one of the most potent and selective COX-2 inhibitor in this series.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Celecoxib	Prostaglandin G/H synthase 2	IC 50 (nM)	80	N/A	N/A	Details
Indomethacin	Prostaglandin G/H synthase 2	IC 50 (nM)	9	N/A	N/A	Details