Transformation of a selective factor Xa inhibitor rivaroxaban into a dual factor Xa/thrombin inhibitor by modification of the morpholin-3-one moiety

Abstract

Replacement of the P₄ morpholin-3-one moiety in a selective factor Xa inhibitor rivaroxaban by 2-ethoxycarbonylpiperidine resulted in a dual factor Xa/thrombin inhibitor 24, possessing a K_i of 62 ± 18 nM for factor Xa and a K_i of 353 ± 75 nM for thrombin. Presented rationalization of dual activity provides a good starting point for “designing in” thrombin inhibitory activity to potent factor Xa inhibitor rivaroxaban.