Design, synthesis and antithrombotic evaluation of novel dabigatran prodrugs containing methyl ferulate

  • Bioorg Med Chem Lett. 2013 Apr 1;23(7):2089-92. doi: 10.1016/j.bmcl.2013.01.126.
Xiao-Zhi Yang  1 ,  Xiao-Juan Diao ,  Wen-Hui Yang ,  Feng Li ,  Guang-Wei He ,  Guo-Qing Gong ,  Yun-Gen Xu
Affiliations
  • 1. Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
PMID: 23466230 DOI: 10.1016/j.bmcl.2013.01.126
Abstract

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).