Design and synthesis of 3,4-methylenedioxy-6-nitrophenoxyacetylhydrazone derivatives obtained from natural safrole: new lead-agents with analgesic and antipyretic properties.
In this work, we reported the synthesis and evaluation of the analgesic, anti-inflammatory, and antipyretic properties of new 2-(6-nitro-benzo[1,3]dioxol-5-yloxy)-acetylhydrazone derivatives (3), designed exploring molecular hybridization and isosteric replacement approaches between nimesulide (1) and carbanalogue NAH series (2) developed at LASSBio. Target compounds were synthesized in very good yields exploiting abundant Brazilian natural product safrole (4) as starting material. The evaluation of the antinociceptive properties of this series led us to discover a new potent prototype of analgesic and antipyretic agent, that is, NAH derivative 3c, named LASSBio-891, which showed to be more potent than dipyrone used as standard.
Bezerra-Netto
Heleno J C
HJ
Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21944-971, Brazil.
Lacerda
Daniel I
DI
Miranda
Ana Luisa P
AL
Alves
Hélio M
HM
Barreiro
Eliezer J
EJ
Fraga
Carlos A M
CA
D000700:Analgesics / Q000138:chemical synthesis* / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000138:chemical synthesis* / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D006835:Hydrazones / Q000138:chemical synthesis / Q000494:pharmacology*; D012451:Safrole / Q000031:analogs & derivatives / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000700:Analgesics; D018712:Analgesics, Non-Narcotic; D000893:Anti-Inflammatory Agents; D006835:Hydrazones; D012451:Safrole