Synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing a cleavable moiety with anti-platelet activity

► We coupled dabigatran with HTMP via esterification to afford seven new prodrugs. ► Y-2, One of our compounds, showed more potent activity for inhibiting thrombosis in vivo than that of dabigatran etexilate. ► In a certain sense, ADP-induced platelet aggregation test indicated the more potent activity of Y-2 was due to HTMP. ► Pharmacokinetic evaluation proved that Y-2 could be metabolized into dabigatran and HTMP.