title: Synthesis and pharmacological evaluation of peptide-mimetic protease-activated receptor-1 antagonists containing novel heterocyclic scaffolds.
abstract: Protease-activated receptor-1 (PAR-1) is a G-coupled receptor activated by alpha-thrombin and other proteases. In this paper we describe the synthesis and the pharmacological evaluation of novel peptide-mimetic antagonists (compounds 1-16) characterized by the presence of new heterocyclic nuclei such as 2-methyl-indole (5- and 6-substituted) and 1,4-benzodiazepine moiety. The new derivatives, tested in order to evaluate their antagonist potency by using human platelet aggregation induced by PAR-1AP, resulted in some cases (compounds 1 and 4) more potent than the reference. The compounds, tested on aortic rings, confirmed the results obtained in the aggregation assay.
authors.affiliation: Dipartimento di Chimica Farmaceutica e Tossicologica, Università degli Studi di Napoli Federico II Via D. Montesano, 49, 80131 Napoli, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Severino
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Fiorino
authors.forename: Elisa
authors.initials: E
authors.lastname: Perissutti
authors.forename: Francesco
authors.initials: F
authors.lastname: Frecentese
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Santagada
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Caliendo
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D018716:Molecular Mimicry; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors
chemical_list: D006571:Heterocyclic Compounds; D007211:Indoles; D010455:Peptides; D011480:Protease Inhibitors; D010975:Platelet Aggregation Inhibitors