(Benzylideneamino)triazole-Thione Derivatives of Flurbiprofen: An Efficient Microwave-Assisted Synthesis and In Vivo Analgesic Potential.

Abstract

Triazole is an imperative heterocycle renowned for its broad-spectrum biological significance. In this manuscript, facile microwave-assisted synthesis of a series of 4-(benzylideneamino)-3-(1-(2-fluoro-[1,1′-biphenyl]-4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione 6(a–m) derivatives along with their in vivo analgesic activity is reported. 2-(2-Fluoro-[1,1′-biphenyl]-4-yl)propanoic acid (flurbiprofen) was converted to methyl 2-(2-fluoro-[1,1′-biphenyl]-4-yl)propanoate using microwave irradiation, followed by its hydrazinolysis with hydrazine monohydrate. 2-(2-Fluoro-[1,1′-biphenyl]-4-yl)propanehydrazide thus obtained was converted to 4-amino-3-(1-(2-fluoro-[1,1′-biphenyl]-4-yl)ethyl)-1H-1,2,4-triazole-5(4H)-thione, followed by its condensation with different aromatic aldehydes to get the title compounds. Structures of all the synthesized compounds were established using different methods (1H NMR and 13C NMR spectroscopies, mass spectrometry, and elemental analysis) and evaluated for their potential as analgesic agents by tail flick, hot plate, and writhing methods. The results of this in vivo study revealed several compounds as potent analgesic agents among which compound 6e showed significant analgesic effect for all the three assays employed.