Title:Synthesis of a Novel Class of 1,3-oxathiolane Nucleoside Derivatives of T- 705 and Evaluation of Their Anti-influenza A Virus and Anti-HIV Activity
Volume: 14
Issue: 6
Author(s): Mingming Han, Xu Zhao, Xuedong Wu, Wei Huang, Xingzhou Li*Fang Yu*
Affiliation:
- Laboratory of Computer-Aided Drug Design & Discovery, Beijing Institute of Pharmacology and Toxicology, Beijing 100850,China
- College of Chemistry, Chemical Engineering and Environmental Engineering, Liaoning Shihua University, Fushun 113001,China
Keywords:
Nucleotide analog, favipiravi, anti-influenza, anti-HIV, 1, 3-oxathiolane nucleoside, viral enzymes.
Abstract: Background: T-705 (Favipiravir) is a broad spectrum antiviral agent approved for stockpiling
in Japan and currently in Phase 3 testing in the United States. Against influenza, it acts as a
prodrug, converted intracellularly to selectively inhibit viral RNA-dependent RNA polymerase or
similar enzymes. This is regarded as a novel antiviral mechanism of action, reducing crossresistance
to other existing anti-influenza drugs.
Objective: To develop new analogs, a class of 1,3-oxathiolane nucleoside derivatives of T-705 was
designed and synthesized in this work.
Results: Anti-influenza activity and Anti-HIV activity of these compounds were evaluated. Compound
1a displayed activity against A H1N1 with an IC50 of 40.4 µmol/L. Compound 1b showed
weak activity against HIV with a viral suppression rate of 70-80% at 30 µmol/L.
Conclusion: A class of 1,3-oxathiolane nucleoside derivatives of T-705 was designed and synthesized,
and one of them was identified as a novel scaffold against viral infection.
