Novel dabigatran derivatives with a fluorine atom at the C-2 position of the terminal benzene ring: Design, synthesis and anticoagulant activity evaluation

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• 作者：Haoran Yang ; Qianqian Liu ; Xiaodong Gao ; Yujie Ren ; ^{clab@sit.edu.cn} ; Yonghong Gao
• 关键词：Anticoagulant activity ; Fluorinated dabigatran derivatives ; Molecular docking ; Synthesis
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2017
• 出版时间：27 January 2017
• 年：2017
• 卷：126
• 期：Complete
• 页码：799-809
• 全文大小：1514 K
• 卷排序：126

文摘

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.