Synthesis and evaluation of novel amidate prodrugs of PMEA and PMPA

Authors
Ballatore, C McGuigan, C De Clercq, E Balzarini, J
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.