RESUMEN

Replacement of the noragmatine group in thrombin inhibitors with a beta-alanyl-guanidine group resulted in a nearly equipotent and more selective compound 8 despite the fact that the pKa of this P1 moiety is five orders of magnitude lower. Further modification resulted in a nonpeptide inhibitor with this beta-alanyl-guanidine group, compound 28. This is an active and selective thrombin inhibitor and in view of its nonpeptide/low basicity structure selected for further pharmacological studies.

Asunto(s)

Antitrombinas/química , Guanidina/análogos & derivados , Antitrombinas/farmacología , Guanidina/química , Guanidina/farmacología , Relación Estructura-Actividad , Trombina/farmacología , Tripsina/farmacología