Design, synthesis and evaluation of novel oxazaphosphorine prodrugs of 9-(2-phosphonomethoxyethyl)adenine (PMEA, adefovir) as potent HBV inhibitors

A series of novel oxazaphosphorine prodrugs of PMEA is disclosed. l-valine methyl ester (7c) demonstrated highly potent anti-HBV activity, excellent stability in human plasma and release of the parent compound PMEA in human microsomes.