Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine

9-(2-Phosphonylmethoxyethyl)adenine (PMEA; 1) was acylated with chloromethyl pivalate to afford bis(pivaloyloxymethyl) PMEA (2). The ester prodrug demonstrated enhanced in vitro potency against HSV-2 greater than 150-fold higher than the parent compound. The antiviral activity of 2 was 50-fold bette...

Full description

Saved in:
Bibliographic Details
Published inAntiviral research Vol. 19; no. 3; p. 267
Main Authors Starrett, Jr, J E, Tortolani, D R, Hitchcock, M J, Martin, J C, Mansuri, M M
Format Journal Article
LanguageEnglish
Published Netherlands 01.09.1992
Subjects
Adenine - analogs & derivatives
Adenine - chemical synthesis
Adenine - pharmacology
Antiviral Agents - chemical synthesis
Antiviral Agents - pharmacology
Cell Line
Cytomegalovirus - drug effects
Drug Evaluation, Preclinical
HIV - drug effects
Humans
Organophosphonates
Prodrugs - chemical synthesis
Prodrugs - pharmacology
Simplexvirus - drug effects
Online AccessGet more information

Cover

More Information
Summary:9-(2-Phosphonylmethoxyethyl)adenine (PMEA; 1) was acylated with chloromethyl pivalate to afford bis(pivaloyloxymethyl) PMEA (2). The ester prodrug demonstrated enhanced in vitro potency against HSV-2 greater than 150-fold higher than the parent compound. The antiviral activity of 2 was 50-fold better than PMEA against HSV-1, and equipotent against HIV and HCMV. The toxicity of 2 was studied in both resting and growing cells.
ISSN:0166-3542
DOI:10.1016/0166-3542(92)90084-I