(Benzylideneamino)triazole–Thione Derivatives of Flurbiprofen: An Efficient Microwave-Assisted Synthesis and <i>In Vivo</i> 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)-1<i>H</i>-1,2,4-triazole-5(4<i>H</i>)-thione <b>6</b>(<b>a-m</b>) derivatives along with their <i>in vivo</i> 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)-1<i>H</i>-1,2,4-triazole-5(4<i>H</i>)-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 <i>in vivo</i> study revealed several compounds as potent analgesic agents among which compound <b>6e</b> showed significant analgesic effect for all the three assays employed.