Highly functionalized 2-oxopiperazine-based peptidomimetics: An approach to PAR1 antagonists
| Autor: | Pilar Ventosa-Andrés, Ángel M. Valdivielso, Marta Gutiérrez-Rodríguez, Ioannis Pappos, M. Ángeles Fernández-Ibáñez, Francisco Tato, Rosario Herranz, Nikos E. Tsopanoglou, M. Teresa García-López |
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| Rok vydání: | 2013 |
| Předmět: |
Agonist
Platelet Aggregation Peptidomimetic Stereochemistry medicine.drug_class PAR1 antagonists Cytotoxicity Molecular Conformation Antineoplastic Agents Ring (chemistry) Piperazines Structure-Activity Relationship Cell Line Tumor Drug Discovery medicine Humans Moiety Receptor PAR-1 Platelet antiaggregant activity Cell Proliferation Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug Chemistry Organic Chemistry α-Amino nitriles Regioselectivity General Medicine Amino acid Surface modification Peptidomimetics Drug Screening Assays Antitumor 2-Oxopiperazines HT29 Cells |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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