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2000
Volume 12, Issue 8
  • ISSN: 1573-4064
  • E-ISSN: 1875-6638

Abstract

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 Naryl- 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.

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/content/journals/mc/10.2174/1573406412666160314151900
2016-12-01
2025-06-01
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