Exploring the Phe-Gly Dipeptide-Derived Piperazinone Scaffold in the Search for Antagonists of the Thrombin Receptor PAR1

Molecules

Ángel M. Valdivielso¹  M. Teresa Garc໚-López¹  Marta Gutiérrez-Rodríguez¹ 

[1] Instituto de Química Médica (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain;

关键词: peptidomimetics;    regioselectivity;    piperazinones;    platelet antiaggregant activity;    PAR1 antagonists;   

DOI  :  10.3390/molecules19044814

来源: mdpi

【 摘 要 】

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 N_1-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.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.