Synthesis and pharmacological evaluation of novel antinociceptive N-substituted-phenylimidazolyl-4-acylhydrazone derivatives

Farmaco. 2002 Dec;57(12):999-1007. doi: 10.1016/s0014-827x(02)01286-7.

Abstract

This paper describes recent results of design, synthesis and pharmacological evaluation of new N-heterocyclic functionalized N-acylhydrazone compounds (NAH), belonging to the N-substituted-phenylimidazolyl-4-acylhydrazone class (3a-o). These compounds were planned by applying the molecular hybridization strategy to propose the structural modifications on the previously described functionalized 2-methyl-imidazolyl-3-acylhydrazone class (2), which presented an important analgesic profile. This new series (3) was synthesized in order to investigate the possible pharmacophoric contribution of the N-heteroaromatic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 3g and 3n are the most potent analgesic agents from this series, at the screening dose of 100 mg/kg p.o. and compounds 3e, 3j and 3o presented the best antiinflammatory properties at the same screening concentration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / administration & dosage
  • Analgesics / chemical synthesis*
  • Analgesics / pharmacology*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Disease Models, Animal
  • Edema / drug therapy
  • Female
  • Hydrazones / administration & dosage
  • Hydrazones / chemical synthesis*
  • Hydrazones / pharmacology*
  • Imidazoles / administration & dosage
  • Imidazoles / chemical synthesis*
  • Imidazoles / pharmacology*
  • Male
  • Mice
  • Pain / drug therapy
  • Rats

Substances

  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Hydrazones
  • Imidazoles