Synthesis and antiviral activity of phosphoralaninate derivatives of methylenecyclopropane analogues of nucleosides.
Antiviral Res
; 43(1): 37-53, 1999 Aug.
Article
de En
| MEDLINE
| ID: mdl-10480262
ABSTRACT
Phenylmethylphosphoro-L-alaninate prodrugs of antiviral Z-methylenecyclopropane nucleoside analogues and their inactive E-isomers were synthesized and evaluated for their antiviral activity against HCMV, HSV-1, HSV-2, HHV-6, EBV, VZV, HIV-1 and HBV. The adenine Z-analogue was a potent inhibitor of all these viruses but it displayed cellular toxicity. The guanine Z-derivative was active against HCMV, HBV, EBV and VZV and it was not cytotoxic. The 2,6-diaminopurine analogue was the most potent against HIV-1 and HBV and somewhat less against HHV-6, HCMV, EBV and VZV in a non-cytotoxic concentration range. The 2-amino-6-cyclopropylamino and 2-amino-6-methoxypurine prodrugs were also more active than parent analogues against several viruses but with a less favorable cytotoxicity profile. In the E-series of analogues, adenine derivative was active against HIV-1, HBV and EBV, and it was non-cytotoxic. The guanine analogue exhibited a significant effect only against HBV. The 2,6-diaminopurine E-analogue was inactive with the exception of a single EBV assay. The 2-amino-6-methoxypurine Z-methylenecyclopropane nucleoside analogue was an effective inhibitor of HCMV, MCMV and EBV. The 2,6-diaminopurine Z-prodrug seems to be the best candidate for further development.
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Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Antiviraux
/
Promédicaments
/
Cyclopropanes
/
Alanine
Limites:
Humans
Langue:
En
Journal:
Antiviral Res
Année:
1999
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique