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
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