Synthesis and biological evaluation of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines as anti-inflammatory and antimicrobial agents

• Efficient regiospecific synthesis of 7-trifluoromethylpyrazolo[1,5-a]pyrimidines.
• Structures established on the basis of 1H, 13C, 19F NMR spectra and IR data.
• Isolation and characterization of an intermediate in DCM at −15 °C.
• Compound 4e exhibited anti-inflammatory activity comparable to the standard drug.
• Promising antimicrobial activity against Gram +ve bacteria and pathogenic fungi.

A series of 2-H/methyl-3-phenyl-5-alkyl/aryl/heteroaryl-7-trifluoromethylpyrazolo[1,5-a]pyrimidines (4a–l) were synthesized by refluxing 3(5)-amino-4-phenyl-5(3)-H/methyl-1H-pyrazoles (1–2) with trifluoromethyl-β-diketones (3a–f) in ethanol for 6 h. The structure of the compounds was assigned on the basis of 1H, 13C, 19F NMR and IR spectral data. The intermediate, 5-methyl-4-phenyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidin-5,7-diol (5b), involved in the reaction was also isolated and characterized in one case by performing the reaction in DCM at −15 °C. A total of nine compounds 4a–f, 4h–i, 4k were tested for their anti-inflammatory activity by Carrageenan-induced rat paw edema assay. Compound 4e exhibited the comparable anti-inflammatory activity (83.4%) to the standard drug Indomethacin (84.2%). To rationalize the anti-inflammatoy activity, docking experiments were performed to study the ability of these compounds to bind into the active site of COX-2 enzyme. All the twelve compounds synthesized (4a–l) were screened for their antimicrobial activity in vitro against two Gram +ve, two Gram −ve bacteria and two fungi. Preliminary results reveal that some of the synthesized compounds revealed promising antimicrobial activity against Gram +ve bacteria and pathogenic fungi used in this study.

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