title: Exploring the Phe-Gly dipeptide-derived piperazinone scaffold in the search for antagonists of the thrombin receptor PAR1.
abstract: A series of Phe-Gly dipeptide-derived piperazinones containing an aromatic urea moiety and a basic amino acid has been synthesized and evaluated as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cells. The synthetic strategy involves coupling of a protected basic amino acid benzyl amide to 1,2- and 1,2,4-substituted-piperazinone derivatives, through a carbonylmethyl group at the N1-position, followed by formation of an aromatic urea at the exocyclic moiety linked at the C2 position of the piperazine ring and removal of protecting groups. None of the compounds showed activity in the biological evaluation.
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. angel@iqm.csic.es.
authors.forename: Ángel M
authors.initials: ÁM
authors.lastname: Valdivielso
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. iqmgl37@iqm.csic.es.
authors.forename: M Teresa
authors.initials: MT
authors.lastname: García-López
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. mgutierrez@iqm.csic.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Gutiérrez-Rodríguez
authors.affiliation: Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain. rosario@iqm.csic.es.
authors.forename: Rosario
authors.initials: R
authors.lastname: Herranz
mesh_terms: D004151:Dipeptides / Q000737:chemistry*; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry; D057786:Peptidomimetics / Q000138:chemical synthesis / Q000737:chemistry*; D010879:Piperazines / Q000737:chemistry*; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000737:chemistry*; D044463:Receptor, PAR-1 / Q000737:chemistry*; D013237:Stereoisomerism; D013917:Thrombin / Q000737:chemistry; D014508:Urea / Q000737:chemistry
chemical_list: D004151:Dipeptides; D010446:Peptide Fragments; D057786:Peptidomimetics; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D044463:Receptor, PAR-1; C082835:thrombin receptor peptide (42-47); D014508:Urea; D013917:Thrombin
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