Design, synthesis, biological evaluation and molecular docking of novel substituted 1-ethyl-1H-benzimidazole fluorinated derivatives as thrombin inhibitors

Six novel substituted 1-ethyl-1H-benzimidazole fluorinated derivatives were designed and synthesised based on computer-aided simulation. The structures of the target compounds were characterised by 1H NMR, 13C NMR, 19F NMR and FT-ICR-MS. The preliminary screening inhibition rate data of synthesised compounds were more than 80 %. Compounds 12a and 12f were evaluated for their anti-thrombin activity in vitro (IC50). The tested data indicated that the compounds showed better thrombin inhibitory activity than reference drug argatroban (9.88 ± 2.26 nM). Especially, compound 12f was the most potent derivative with an IC50 of 3.21 ± 0.57 nM and could act as a candidate compound for further exploration of thrombin inhibitor.