Design and synthesis of novel potent antinociceptive agents: methyl-imidazolyl N-acylhydrazone derivatives.
This paper describes recent results of design, synthesis and pharmacological 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 functionalized 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-heteroaromatic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 4a-b are the most potent antinociceptive agents from this series.
Figueiredo
J M
JM
Laboratorio de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Rio de Janeiro, RJ, Brazil.
Câmara
C A
CA
Amarante
E G
EG
Miranda
A L
AL
Santos
F M
FM
Rodrigues
C R
CR
Fraga
C A
CA
Barreiro
E J
EJ
D019342:Acetic Acid; D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D002351:Carrageenan; D003085:Colic / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D015195:Drug Design; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D051379:Mice; D023421:Models, Animal; D051381:Rats; D013329:Structure-Activity Relationship
D000700:Analgesics; D006571:Heterocyclic Compounds; D006835:Hydrazones; D007093:Imidazoles; D002351:Carrageenan; D019342:Acetic Acid