Design, synthesis, biological evaluation and molecular docking of novel dabigatran derivatives as potential thrombin inhibitors

Abstract

A series of dabigatran derivatives were designed and synthesized to discover effective thrombin inhibitors. All the target compounds were characterized by ¹H NMR, ¹³C NMR and HRMS. These compounds were evaluated in vitro and showed potent anticoagulant activities against thrombin. Among these compounds, the ethyl group substitution at N-1 of benzimidazole exhibited better anticoagulant activity against thrombin. Especially, compound 10i showed an IC₅₀ of 2.04 nM. Docking simulations demonstrated that compound 10i could bind tightly with the crystal structure of the thrombin active site. Based on the results obtained, compound 10i may act as a candidate compound for further development of direct thrombin inhibitors.