Advances in nucleoside monophosphate prodrugs as anti-HCV agents

• Authors: Drew R. Bobeck, RFS Pharma, LLC; Raymond Schinazi, Emory University; Steven Coats, Emory University
• Journal Title: ANTIVIRAL THERAPY
• Volume: Volume 15, Number 7
• Publisher: INT MEDICAL PRESS LTD | 2010-01-01, Pages 935-950
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.3851/IMP1667
• Subjects: Health Sciences, Pharmacology; Health Sciences, Pharmacy; Biology, Virology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Infectious Diseases; Pharmacology & Pharmacy; Virology; HEPATITIS-C VIRUS; PHOSPHORAMIDATE PROTIDE APPROACH; HEPDIRECT PRODRUGS; RNA REPLICATION; INACTIVE NUCLEOSIDE; POTENT INHIBITORS; NS5B POLYMERASE; IN-VITRO; INFECTION; THERAPY

Abstract

Nucleoside monophosphate prodrugs that are eventually bioconverted to the active nucleoside triphosphate (NTP) offer the potential to deliver increased intracellular NTP levels and/or organ-specific NTP enhancement. There are several classes of monophosphate prodrugs that have been applied to HCV drug discovery, and some of these approaches are currently being evaluated in humans. This review discusses recent advances in monophosphate prodrug approaches to improve oral absorption, stability and pharmacokinetic profile, including their advantages and potential pitfalls. ©2010 International Medical Press.