RESUMEN

N-aralkylpyroglutamides of substituted bispidine were prepared and evaluated for their ability to inhibit collagen induced platelet aggregation, both in vivo and in vitro. Some compounds showed high anti-platelet efficacy (in vitro) of which six inhibited both collagen as well as U46619 induced platelet aggregation with concentration dependent anti-platelet efficacy through dual mechanism. In particular, the compound 4j offered significant protection against collagen epinephrine induced pulmonary thromboembolism as well as ferric chloride induced arterial thrombosis, without affecting bleeding tendency in mice. Therefore, the present study suggests that the compound 4j displays a remarkable antithrombotic efficacy much better than aspirin and clopidogrel.

Asunto(s)

Plaquetas/efectos de los fármacos , Compuestos Bicíclicos Heterocíclicos con Puentes/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Embolia Pulmonar/prevención & control , Ácido Pirrolidona Carboxílico/uso terapéutico , Trombosis/prevención & control , Animales , Coagulación Sanguínea/efectos de los fármacos , Plaquetas/patología , Compuestos Bicíclicos Heterocíclicos con Puentes/efectos adversos , Compuestos Bicíclicos Heterocíclicos con Puentes/síntesis química , Compuestos Bicíclicos Heterocíclicos con Puentes/química , Hemorragia/inducido químicamente , Humanos , Ratones , Adhesividad Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/síntesis química , Inhibidores de Agregación Plaquetaria/química , Embolia Pulmonar/sangre , Embolia Pulmonar/patología , Ácido Pirrolidona Carboxílico/efectos adversos , Ácido Pirrolidona Carboxílico/síntesis química , Ácido Pirrolidona Carboxílico/química , Trombosis/sangre , Trombosis/patología