Novel dabigatran derivatives with a fluorine atom at the C-2 position of the terminal benzene ring: Design, synthesis and anticoagulant activity evaluation
Fifteen novel fluorinated dabigatran derivatives were designed and synthesized. In the experimental part, recrystallization was used to simplify the operation. Eleven compounds efficiently inhibited thrombin at nanomolar levels in vitro. Compound 7k showed the best inhibitory activity against thrombin (IC50 = 0.84 nM). Computational studies were performed to explain the inhibitory mechanism.