Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA

Citation
C. Ballatore et al., Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA, BIOORG MED, 11(8), 2001, pp. 1053-1056
Citations number
18
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
ISSN journal
0960894X → ACNP
Volume
11
Issue
8
Year of publication
2001
Pages
1053 - 1056
Database
ISI
SICI code
0960-894X(20010423)11:8<1053:SAEONA>2.0.ZU;2-2
Abstract
Some novel amidate prodrugs of PMEA and PMPA have been synthesised and test ed in vitro for their biological activity. Compound 5 in particular showed greatly enhanced antiviral potency compared with the parent nucleotide anal ogue. In vitro enzymatic studies and structure-activity relationships indic ate that the degradation mechanism of such prodrugs may be the same as that described for the phosphoramidate triesters of nucleotide analogues. (C) 2 001 Elsevier Science Ltd. All rights reserved.