Design and synthesis of novel potent antinociceptive agents: Methyl-imidazolyl N-acylhydrazone derivatives

This paper describes recent results of design, synthesis and pharmacologica l evaluation of new N-heterocyclic functionalized N-acylhydrazone compounds , belonging to the 2-methyl-imidazolyl-3-acylhydrazone class (4a-e). These compounds were planned by applying the molecular simplification strategy to propose the structural modifications on the previously described functiona lized imidazo[1,2-a]pyridine 3-acylhydrazone series (2), which presented an important analgesic profile. This new series (4) was synthesized in order to investigate the possible pharmacophoric contribution of the N-heteroarom atic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 4a-b are the most potent antinociceptive agents from this series. (C) 2000 Elsevier Science Ltd. All rights reserved.