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

  • Eur J Med Chem. 2012 Nov:57:21-8. doi: 10.1016/j.ejmech.2012.09.016.
Xiao-Zhi Yang  1 ,  Wen-Hui Yang ,  Yun-Gen Xu ,  Xiao-Juan Diao ,  Guang-Wei He ,  Guo-Qing Gong
Affiliations
  • 1. Department of Medicinal Chemistry, China Pharmaceutical University, Tongjiaxiang 24, Nanjing 210009, China.
PMID: 23043765 DOI: 10.1016/j.ejmech.2012.09.016
Abstract

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).