SYNTHESIS, BIOLOGICAL-ACTIVITY AND DECOMPOSITION STUDIES OF AMINO-ACID PHOSPHOMONOESTER AMIDATES OF ACYCLOVIR

Authors
ABRAHAM TW MCINTEE EJ IYER VV SCHINAZI RF WAGNER CR
Citation
Tw. Abraham et al., SYNTHESIS, BIOLOGICAL-ACTIVITY AND DECOMPOSITION STUDIES OF AMINO-ACID PHOSPHOMONOESTER AMIDATES OF ACYCLOVIR, Nucleosides & nucleotides, 16(10-11), 1997, pp. 2079-2092
Citations number
41
Journal title
Nucleosides & nucleotides → ACNP
ISSN journal
07328311
Volume
16
Issue
10-11
Year of publication
1997
Pages
2079 - 2092
Database
ISI
SICI code
0732-8311(1997)16:10-11<2079:SBADSO>2.0.ZU;2-5
Abstract
Highly stable and water soluble amino acid phosphomonoester amidates o f acyclovir (ACV) were synthesized and shown to function predominantly as prodrugs of ACV and not acyclovir monophosphate (ACV-MP) with acti vities within two fold of the amino acid prodrug of ACV, valaciclovir (VACV). Metabolism studies revealed that incubation of cell-free extra cts of Vero cells with the L-leucine phosphomonoester amidate of ACV ( 3c), resulted in a burst of ACV-MP production followed by the rapid ge neration of ACV.