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.

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

Graphical Abstract