title: Synthesis and antiplatelet evaluation of novel aryl-sulfonamide derivatives, from natural safrole.
abstract: In the scope of a research program aiming at the synthesis and pharmacological evaluation of novel possible antiplatelet prototype compounds, exploring bioisosterism principles for molecular design, we describe in this paper the synthesis of new aryl-sulfonamides derivatives, structurally similar to known thromboxane A2 receptor antagonists. The synthetic route used to access the new compounds described herein starts from safrole, an abundant Brazilian natural product, which occurs in Sassafras oil (Ocotea pretiosa). The results from preliminary evaluation of these novel aryl-sulfonamide compounds by the platelet aggregation inhibitory test, using rabbit PRP, induced by ADP, collagen, arachidonic acid, and U46619, identified the N-[2-(4-carboxymethoxyphenyl)ethyl]-6-methyl-3,4-methylenedioxyphe nyl- sulfonamido derivative as the most active among them, presenting in IC50 value for the U-46619-induced platelet aggregation in rabbit platelet-rich plasma: 329 microM.
authors.affiliation: Laboratório de Avaliação e Síntese de Substâncias Bioativas, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Brazil.
authors.forename: L M
authors.initials: LM
authors.lastname: Lima
authors.forename: C B
authors.initials: CB
authors.lastname: Ormelli
authors.forename: F F
authors.initials: FF
authors.lastname: Brito
authors.forename: A L
authors.initials: AL
authors.lastname: Miranda
authors.forename: C A
authors.initials: CA
authors.lastname: Fraga
authors.forename: E J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D000818:Animals; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D011817:Rabbits; D012451:Safrole / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D010975:Platelet Aggregation Inhibitors; D013449:Sulfonamides; D012451:Safrole