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Antimicrob Agents Chemother. 2009 Jun;53(6):2660-2. doi: 10.1128/AAC.01546-08. Epub 2009 Mar 16.

The octadecyloxyethyl ester of (S)-9-[3-hydroxy-2-(phosphonomethoxy) propyl]adenine is a potent and selective inhibitor of hepatitis C virus replication in genotype 1A, 1B, and 2A replicons.

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1
San Diego Veterans Medical Research Foundation and the Department of Medicine, Division of Infectious Disease, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0676, USA.

Abstract

The octadecyloxyethyl (ODE) and hexadecyloxypropyl (HDP) esters of (S)-9-[3-hydroxy-2-(phosphonomethoxy)propyl]adenine (HPMPA) are potent inhibitors of orthopoxvirus, herpesvirus, human immunodeficiency virus type 1, and hepatitis B virus replication in vitro. HDP and ODE esters of (S)-HPMPA and (R)-HPMPA were evaluated for their activity in hepatitis C virus (HCV) replicon assays using luciferase (1B and 2A replicons) or RNA (1B) quantification. The ODE ester of (S)-HPMPA [ODE-(S)-HPMPA] was the most active compound, with 50% effective concentrations (EC(50)s) in the 0.69 to 1.31 microM range. HDP and ODE esters of (R)-HPMPA were severalfold less active, while (S)-HPMPA and (R)-HPMPA were inactive. In genotype 1A and 1B replicons analyzed by HCV RNA analysis, ODE-(S)-HPMPA was the most active compound, with EC(50)s of 1.8 and 2.1 microM, respectively.

PMID:
19289518
PMCID:
PMC2687240
DOI:
10.1128/AAC.01546-08
[Indexed for MEDLINE]
Free PMC Article
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