title: Synthesis and in vitro evaluation of a phosphonate prodrug: bis(pivaloyloxymethyl) 9-(2-phosphonylmethoxyethyl)adenine.
abstract: 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.
authors.affiliation: Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492.
authors.forename: J E
authors.initials: JE
authors.lastname: Starrett
authors.forename: D R
authors.initials: DR
authors.lastname: Tortolani
authors.forename: M J
authors.initials: MJ
authors.lastname: Hitchcock
authors.forename: J C
authors.initials: JC
authors.lastname: Martin
authors.forename: M M
authors.initials: MM
authors.lastname: Mansuri
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006678:HIV / Q000187:drug effects; D006801:Humans; D063065:Organophosphonates; D011355:Prodrugs / Q000138:chemical synthesis* / Q000494:pharmacology*; D018139:Simplexvirus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D063065:Organophosphonates; D011355:Prodrugs; C053001:adefovir; D000225:Adenine