Synthesis and analgesic activity of novel N-acylarylhydrazones and isosters, derived from natural safrole

A new series of antinociceptive compounds belonging to the N-acylarylhydraz one (NAH) class were synthesized from natural safrole (7). The most analges ic derivative represented by 10f, [(4'-N,N-dimethylaminobenzylidene-3-(3',4 '-methylenedioxyphenyl)-propionylhydrazine], was more potent than dipyrone and indomethacin, used as standards. The NAH compounds described herein wer e structurally planned by molecular hybridization and classical bioisosteri sm strategies on previously reported analgesic NAH in order to identify the pharmacophoric contribution of the N-acylarylhydrazone moiety and investig ate the structure-activity relationship (SAR) in these series. (C) 2000 Edi tions scientifiques et medicales Elsevier SAS.