Advances in nucleoside monophosphate prodrugs as anti-HCV agents

• Type of Material: Article
• Authors: Drew R. Bobeck, RFS Pharma, LLC; Raymond Schinazi, Emory University; Steven Coats, Emory University
• Language: English
• Date: 2010-01-01
• Publisher: INT MEDICAL PRESS LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020
• Final Published Version (URL): http://dx.doi.org/10.3851/IMP1667
• Title of Journal or Parent Work: ANTIVIRAL THERAPY
• Volume: 15
• Issue: 7
• Start Page: 935
• End Page: 950
• Grant/Funding Information: This work was supported, in part, by 2P30-AI-050409, R01-AI-076535, 5R37-AI-041980 and 5R37-AI-025899, and by the Center for AIDS Research, Laboratory of Biochemical Pharmacology, Department of Pediatrics, Emory University School of Medicine and Veterans Affairs Medical Center, Decatur, GA, USA (all to RFS).
• Keywords: IN-VITRO; THERAPY; NS5B POLYMERASE; PHOSPHORAMIDATE PROTIDE APPROACH; Science & Technology; Pharmacology & Pharmacy; RNA REPLICATION; INFECTION; HEPDIRECT PRODRUGS; Life Sciences & Biomedicine; Infectious Diseases; INACTIVE NUCLEOSIDE; HEPATITIS-C VIRUS; POTENT INHIBITORS; Virology
• Research Categories: Health Sciences, Pharmacology; Biology, Virology; Health Sciences, Pharmacy

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.