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

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.

Cite this article as:

Han Mingming , Zhao Xu, Wu Xuedong, Huang Wei , Li Xingzhou*, Yu Fang *, 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, Medicinal Chemistry 2018; 14 (6) . https://dx.doi.org/10.2174/1573406414666180112102225