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

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Abstract

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.

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Acknowledgments

This work was supported by the Science and Technology Commission of Shanghai Municipality (13DZ1930402, 13DZ 1930403).

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Authors and Affiliations

  1. School of Chemical and Environmental Engineering, Shanghai Institute of Technology, No. 100, Haiquan Road, Fengxian District, Shanghai, 201418, China

    Fei Wang & Yu-Jie Ren

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  1. Fei Wang
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  2. Yu-Jie Ren
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Correspondence to Yu-Jie Ren.

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Wang, F., Ren, YJ. Design, synthesis, biological evaluation and molecular docking of novel substituted 1-ethyl-1H-benzimidazole fluorinated derivatives as thrombin inhibitors. J IRAN CHEM SOC 13, 1155–1166 (2016). https://doi.org/10.1007/s13738-016-0830-1

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  • DOI: https://doi.org/10.1007/s13738-016-0830-1

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