ETHER, CARBONATE AND URETHANE DEOXYNUCLEOSIDE DERIVATIVES AS PRODRUGS

3'-Deoxythymidine and its 3'-azido derivative, 2',3'-dideoxycytidine, 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine have been acylated to form carbonates and methanes in chemoselective reactions. The nucleosi des have been N- and/or O-alkylated by alpha-chloroethyl or chlorometh yl alkyl carbonates to form alpha-alkyloxycarbonyloxyethyl or alkyloxy carbonyloxymethyl derivatives. The products are lipophilic in order to facilitate transport through biological membranes and are designed to be cleaved by esterases with liberation of the bioactive nucleoside. Initial esterase cleavage of the alkylated derivatives produces hemiac etals or -aminals which subsequently dissociate to the active nucleosi de.