Protease-activated receptor-1 (PAR-1) is a G-coupled receptor activated by a-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.
Synthesis and pharmacological evaluation of peptide-mimetic protease-activated receptor-1 antagonists containing novel heterocyclic scaffolds / Severino, Beatrice; Fiorino, Ferdinando; Perissutti, Elisa; Frecentese, Francesco; Cirino, Giuseppe; Roviezzo, Fiorentina; Santagada, Vincenzo; Caliendo, Giuseppe. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 16:11(2008), pp. 6009-6020.
Synthesis and pharmacological evaluation of peptide-mimetic protease-activated receptor-1 antagonists containing novel heterocyclic scaffolds
SEVERINO, BEATRICE;FIORINO, FERDINANDO;PERISSUTTI, ELISA;FRECENTESE, FRANCESCO;CIRINO, GIUSEPPE;ROVIEZZO, FIORENTINA;SANTAGADA, VINCENZO;CALIENDO, GIUSEPPE
2008
Abstract
Protease-activated receptor-1 (PAR-1) is a G-coupled receptor activated by a-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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.