Design, Synthesis and Bioactivity Evaluation of Novel Dabigatran Derivatives as Potential Thrombin Inhibitors

Title:Design, Synthesis and Bioactivity Evaluation of Novel Dabigatran Derivatives as Potential Thrombin Inhibitors

Volume: 13 Issue: 8

Author(s): Qianqian Liu, Yujie Ren and Xiaodong Gao

Affiliation:

Keywords: Dabigatran derivaties, synthesis, antithrombin activity, molecular docking.

Abstract: With the help of computer-aided drug design approach, five dabigatran derivatives were designed and synthesized. The structures of these compounds were elucidated by ¹H NMR, ¹³C NMR, HRMS analyses. All the compounds were evaluated for their thrombin inhibitory activitiy in vitro (IC₅₀) and they showed significant thrombin inhibition with IC₅₀ values from 2.74 to 20.31 nM. Especially, compound 7a, and 7b were potent thrombin inhibitor with IC₅₀ values of 2.74 and 2.99 nM, respectively, which were comporable to dabigatran (1.20 nM) and much better than argatroban (9.88 nM). Moreover, molecular docking study was performed to determine the inhibitory mechanism of active compounds.

Cite this article as:

Liu Qianqian, Ren Yujie and Gao Xiaodong, Design, Synthesis and Bioactivity Evaluation of Novel Dabigatran Derivatives as Potential Thrombin Inhibitors, Letters in Drug Design & Discovery 2016; 13 (8) . https://dx.doi.org/10.2174/1570180813666160622081105

DOI https://dx.doi.org/10.2174/1570180813666160622081105	Print ISSN 1570-1808
Publisher Name Bentham Science Publisher	Online ISSN 1875-628X