title: Design, synthesis and biological evaluation of new peptide-based ureas and thioureas as potential antagonists of the thrombin receptor PAR1.
abstract: By applying a diversity oriented synthesis strategy for the search of new antagonists of the thrombin receptor PAR1, a series of peptide-based ureas and thioureas, including analogues of the PAR1 reference antagonist RWJ-58259, has been designed and synthesized. The general synthetic scheme involves reduction of basic amino acid-derived amino nitriles by hydrogen transfer from hydrazine monohydrate in the presence of Raney Ni, followed by reaction with diverse isocyanates and isothiocyanates, and protecting group removal. All new compounds have been evaluated as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN. Some protected peptide-based ureas displayed significant antagonist activity.
authors.affiliation: Instituto de Química Médica (CSIC), Juan de Cierva 3, 28006 Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Ventosa-Andrés
authors.forename: Angel M
authors.initials: AM
authors.lastname: Valdivielso
authors.forename: Ioannis
authors.initials: I
authors.lastname: Pappos
authors.forename: M Teresa
authors.initials: MT
authors.lastname: García-López
authors.forename: Nikos E
authors.initials: NE
authors.lastname: Tsopanoglou
authors.forename: Rosario
authors.initials: R
authors.lastname: Herranz
mesh_terms: D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010974:Platelet Aggregation / Q000187:drug effects; D012016:Reference Values; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors
chemical_list: D010455:Peptides; D014508:Urea; D010975:Platelet Aggregation Inhibitors