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  • Synthesis and biological evaluation of N-aryl-N'-(5-(2-hydroxybenzoyl)pyrimidin-2-yl)guanidines as toll-like receptor 4 antagonists synthesis of guanidine-based TLR4 antagonists
    Sova, Matej, 1979- ...
    Background: Toll-like receptor 4 (TLR4) has been associated with several inflammatory diseases, such as sepsis, atherosclerosis and chronic pain. Objective: The aim of the present study was to ... develop an efficient and straightforward synthetic approach for the preparation of small-molecule antagonists N-aryl-N%-(5-(2-hydroxybenzoyl)pyrimidin-2-yl)guanidines in order to evaluate these for TLR4 antagonist activity and to obtain useful information about their structure-activity relationships. Methods: The present work have designed and optimized a three-step synthetic route for derivatives of a previously demonstrated antagonist of TLR4: 1-(4-fluorophenyl)-2-(5-(2-hydroxy-5-methoxybenzoyl)pyrimidin-2-yl)guanidine. The antagonist activities of eight novel synthesized compounds were evaluated on cells which selectively express TLR4. Results: Three guanidine derivatives showed promising antagonist activities, with IC50 values in the low micromolar range. Conclusion: Our findings represent an important starting point for further studies of small-molecule agents targeting Toll-like receptors.
    Vir: Medicinal chemistry. - ISSN 1573-4064 (Vol. 12, iss. 8, 2016, str. 742-750)
    Vrsta gradiva - članek, sestavni del
    Leto - 2016
    Jezik - angleški
    COBISS.SI-ID - 4108145

vir: Medicinal chemistry. - ISSN 1573-4064 (Vol. 12, iss. 8, 2016, str. 742-750)
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