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Highly functionalized 2-oxopiperazine-based peptidomimetics: An approach to PAR1 antagonists

By Ángel M. Valdivielso, Pilar Ventosa-Andrés, Francisco Tato, M. Ángeles Fernández-Ibañez, Ioannis Pappos, Nikos E. Tsopanoglou, M. Teresa García-López, Marta Gutiérrez-Rodríguez and Rosario Herranz


A series of pseudodipeptide-based chiral 1,3,4,5-tetrasubstituted-2- oxopiperazines has been designed and synthesized as potential PAR1 antagonists. These highly functionalized piperazines were synthesized from aromatic and basic amino acid derived Ψ[CH(CN)NH]pseudodipeptides through a four step pathway that involves reduction of the cyano group to build the 2-oxopiperazine ring, followed by selective functionalization at the N4-, N 1-positions, and at the exocyclic moiety at position C5. This regioselective functionalization required the fine tuning of reaction conditions. All new compounds were screened as inhibitors of human platelet aggregation induced by the PAR1 agonist SFLLRN and as cytotoxic agents in human cancer cell lines. Some of the compounds displayed moderate PAR1 antagonist activity, while, others were cytotoxic at μM concentration. No correlation was observed between both types of activities.Peer Reviewe

Topics: PAR1 antagonists, Peptidomimetics, 2-Oxopiperazines, α-Amino nitriles, Platelet antiaggregant activity, Cytotoxicity
Publisher: 'Elsevier BV'
Year: 2014
DOI identifier: 10.1016/j.ejmech.2013.09.058
OAI identifier:
Provided by: Digital.CSIC

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