RESUMO
A novel series of prodrugs containing dabigatran and methyl (E)-3-(4-hydroxy-2-methoxyphenyl)propenoate (methyl ferulate) were synthesized. All of them reveal the effect of thrombin-induced anti-platelet aggregation in vitro. In addition, in vivo experiment shows that one of the target compounds, X-2 (ED50=3.7 ± 1.0 µmol/kg) possesses a more potent activity for inhibiting venous thrombosis than that of dabigatran etexilate (ED50=7.8 ± 1.5 µmol/kg).
Assuntos
Desenho de Fármacos , Fibrinolíticos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Pró-Fármacos/farmacologia , Benzimidazóis/química , Benzimidazóis/farmacologia , Ácidos Cafeicos/química , Dabigatrana , Relação Dose-Resposta a Droga , Fibrinolíticos/síntese química , Fibrinolíticos/química , Humanos , Estrutura Molecular , Inibidores da Agregação Plaquetária/síntese química , Inibidores da Agregação Plaquetária/química , Pró-Fármacos/síntese química , Pró-Fármacos/química , Piridinas/farmacologia , Trombina/metabolismo , Trombose Venosa/tratamento farmacológico , beta-Alanina/análogos & derivados , beta-Alanina/químicaRESUMO
A novel series of prodrugs consisting of dabigatran and 2-hydroxymethyl-3,5,6-trimethylpyrazine (HTMP) were synthesized. The pharmacological results show that all of them possess the effect of anti-platelet aggregation induced by thrombin in vitro. Moreover, one of those compounds, Y-2 (ED(50) = 2.1 ± 1.3 mg/kg) shows more potent activity for inhibiting thrombosis in vivo than that of dabigatran etexilate (ED(50) = 4.4 ± 2.2 mg/kg).
