title: Synthesis and anti-platelet activity of novel arylsulfonate--acylhydrazone derivatives, designed as antithrombotic candidates.
abstract: In this work, we describe a new class of promising anti-platelet drug candidates with significant antithrombotic activity in vivo. This new series of compounds was structurally planned by modification of known thrombin inhibitors based on the use of acylhydrazone subunit, as a nonpeptide scaffold, and variations at P1 moiety. Three different families of arylsulfonate-acylhydrazone derivatives were designed. The bioassays indicated the first class of derivatives represented by 4f (LASSBio-693) and 4j (LASSBio-743), which were active in inhibiting the platelet aggregation induced by thrombin. The second class represented by compounds 4e (LASSBio-774) and 4h (LASSBio-480) that selectively inhibit the platelet aggregation involving TXA(2) formation. Finally, the third class of derivatives was identified acting as a novel symbiotic agent able to inhibit the platelet aggregation induced by collagen or AA and by thrombin, represented by compounds 4b (LASSBio-694) and 4g (LASSBio-770).
authors.affiliation: Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Faculdade de Farmácia, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, RJ, PO Box 68006, 21944-910, Brazil. lidia@pharma.ufrj.br
authors.forename: Lídia M
authors.initials: LM
authors.lastname: Lima
authors.forename: Flávia S
authors.initials: FS
authors.lastname: Frattani
authors.forename: Jean L
authors.initials: JL
authors.lastname: Dos Santos
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.forename: Carlos Alberto M
authors.initials: CA
authors.lastname: Fraga
authors.forename: Russolina B
authors.initials: RB
authors.lastname: Zingali
authors.forename: Eliezer J
authors.initials: EJ
authors.lastname: Barreiro
mesh_terms: D006835:Hydrazones / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D013451:Sulfonic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis
chemical_list: D006835:Hydrazones; D010975:Platelet Aggregation Inhibitors; D013451:Sulfonic Acids; D013928:Thromboxane A2