Medicinal chemistry of N-acylhydrazones: new lead-compounds of analgesic, antiinflammatory and antithrombotic drugs.
In this article we provide an overview on the medicinal chemistry of new bioactive N-acylhydrazone (NAH) derivatives designed through the structural optimization of N-arylhydrazone precursors, originally planned by molecular hybridization of two known 5-lipoxygenase inhibitors, i.e. CBS-1108 and BW-755c. The analgesic, antiedematogenic and platelet anti-aggregating profile of several isosteric NAH compounds was investigated by using classical in vivo and ex-vivo pharmacological assays, which allowed the identification of new potent centrally and peripherically-acting analgesic leads, new antiinflammatory agents and new antithrombotic prototypes. During this study, dozens of active NAH compounds were discovered, clarifying the structure-activity relationships for this series of derivatives and indicating the pharmacophoric character of the N-acylhydrazone moiety for its biological profile.
Laboratório de Avaliacao e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, PO Box 68006, Zip Code 21944-971, Rio de Janeiro, RJ, Brazil. cmfraga@pharma.ufrj.br
Carlos A M
CA
Fraga
Eliezer J
EJ
Barreiro
D000700:Analgesics / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000494:pharmacology*; D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D006801:Humans; D006835:Hydrazones / Q000737:chemistry / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006835:Hydrazones; D010975:Platelet Aggregation Inhibitors