Synthesis and antiviral evaluation of fluorinated acyclo-nucleosides and their phosphoramidates

• Type of Material: Article
• Authors: Sawsan Mahmoud, Emory University; Hao Li, Emory University; Tamara R. McBrayer, CocrystalPharma Inc; Leda Bassit, Emory University; Sherif F. Hammad, Helwan University; Steven Coats, Emory University; Franck Amblard, Emory University; Raymond Schinazi, Emory University
• Language: English
• Date: 2017-01-01
• Publisher: TAYLOR & FRANCIS INC
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2016
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1080/15257770.2016.1218023
• Title of Journal or Parent Work: NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
• Volume: 36
• Issue: 1
• Start Page: 66
• End Page: 82
• Grant/Funding Information: This work was supported in part by NIH grant 5P30-AI-50409 (CFAR). We would like to acknowledge the Egyptian Ministry of Higher Education and the Egyptian Educational Culture Bureau in USA for funding Dr. Sawsan’s Ph.D. studies at Emory University. Dr. Schinazi is the Chairman and a major shareholder of CocrystalPharma, Inc. Emory received no funding from CocrystalPharma, Inc. to perform this work and vice versa.
• Keywords: PRODRUGS; antiviral agent; Life Sciences & Biomedicine; acyclonucleoside; VIRUS; Biochemistry & Molecular Biology; Science & Technology; phosphoramidates; Fluorine
• Research Categories: Biology, Virology; Biology, Molecular

Abstract

A novel series of tetrafluoro and hexafluoro acyclic nucleosides and their phosphoramidates were successfully prepared from commercially available 2,2,3,3-tetrafluoro-1,4-butanediol and 2,2,3,3,4,4-hexafluoro-1,5-pentanediol in four to six steps. Their ability to block HIV, HCV, HSV-1, and HBV replication along with their cytotoxicity toward HepG2, human lymphocyte, CEM, and Vero cells was assessed.