Synthesis and pharmacological evaluation of novel antinociceptive N-substituted-phenylimidazolyl-4-acylhydrazone derivatives.
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.
Cunha
Anna C
AC
Laboratório de Avaliação e Sintese de Sustâncias Biotivas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Ilha do Fundão, P. O. Box 68006, 21944-970 Rio de Janeiro RJ, Brazil.
Tributino
Jorge L M
JL
Miranda
Ana L P
AL
Fraga
Carlos A M
CA
Barreiro
Eliezer J
EJ
D000700:Analgesics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy; D005260:Female; D006835:Hydrazones / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D007093:Imidazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010146:Pain / Q000188:drug therapy; D051381:Rats
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006835:Hydrazones; D007093:Imidazoles