Discovery of chromen-7-yl furan-2-carboxylate as a potent and selective factor XIa inhibitor

Research output: Contribution to journalArticle

Authors

External Institution(s)

  • King Saud University
  • Virginia Commonwealth University

Details

Original languageEnglish (US)
Pages (from-to)40-48
Number of pages9
JournalCardiovascular and Hematological Agents in Medicinal Chemistry
Volume15
Issue number1
StatusPublished - Apr 1 2017
Peer-reviewedYes

Abstract

Background: Direct inhibition of coagulation factor XIa (FXIa) carries a significant promise for developing effective and safe anticoagulants. Method: In this report, we studied 4-methyl-2-oxo-2H-chromen-7-yl furan-2-carboxylate 1, a coumarin derivative, for direct FXIa inhibition. Results: This small molecule was found to inhibit FXIa with an IC50 value of 0.77 μM. Coumarin 1 also displayed a moderate-to-high selectivity for FXIa inhibition over other coagulation, digestive, and fibrinolysis serine proteases. Coumarin 1 selectively doubled APTT of human plasma at a concentration of 72 μM. Insights about the structural features that contribute to the unique potential of such small molecule were deduced by profiling similar molecules in PubChem Open Chemistry Database as well as by performing a computational docking exercise. Conclusion: Overall, chromen-7-yl furan-2-carboxylate 1 is expected to serve as an excellent fragmental lead for further anticoagulant design and development.

    Research areas

  • Active site inhibitor, Anticoagulant, Clotting times, Coumarin, Direct inhibition, Factor XIa

Citation formats

APA

Harvard

Obaidullah, AJ & Al-Horani, RA 2017, 'Discovery of chromen-7-yl furan-2-carboxylate as a potent and selective factor XIa inhibitor', Cardiovascular and Hematological Agents in Medicinal Chemistry, vol. 15, no. 1, pp. 40-48. https://doi.org/10.2174/1871525715666170529093938