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Design, Synthesis, and Anti‐Thrombotic Evaluation of Some Novel Fluorinated Thrombin Inhibitor Derivatives
Author(s) -
Chen Haifeng,
Ren Yujie
Publication year - 2015
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.201400460
Subject(s) - argatroban , chemistry , thrombin , discovery and development of direct thrombin inhibitors , stereochemistry , enzyme inhibitor , imidazole , propanoic acid , enzyme , combinatorial chemistry , pharmacology , biochemistry , platelet , medicine , immunology , biology
Computer‐aided simulation was used to design and synthesize nine novel fluorinated thrombin inhibitor derivatives. These compounds were confirmed by spectral analyses ( 1 H NMR, 13 C NMR, and FT‐ICR‐MS). Their inhibitory activities against thrombin enzyme were evaluated by chromogenic assay. All the derivatives demonstrated thrombin inhibitory activity in vitro . Five of these compounds exerted more potent effects against thrombin enzyme compared with the reference drug argatroban. Compound 3‐(2‐(((4‐carbamimidoylphenyl)amino)methyl)‐1‐ethyl‐ N ‐(2‐fluoro‐phenyl)‐1 H ‐benzo[ d ]imidazole‐5‐carboxamido)propanoic acid (IC 50 = 3.52 ± 0.32 nmol/L) was a more potent inhibitor of thrombosis than argatroban (IC 50 = 9.46 ± 0.92 nmol/L).