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 urethanes in chemoselective reactions. The nucleosides have been N- and/or O-alkylated by alpha-chloroethyl or chloromethyl alkyl carbonates to form alpha-alkyloxycarbonyloxyethyl or alkyloxycarbonyloxymethyl 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 hemiacetals or -aminals which subsequently dissociate to the active nucleoside.
Hammer
K
K
Department of Chemistry, University of Oslo, Norway.
Hatlelid
J
J
Grøtli
M
M
Arukwe
J
J
Klaveness
J
J
Rise
F
F
Undheim
K
K
D000998:Antiviral Agents / Q000138:chemical synthesis* / Q000737:chemistry; D002254:Carbonates / Q000138:chemical synthesis; D003853:Deoxyribonucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D004355:Drug Stability; D004987:Ethers / Q000138:chemical synthesis; D006678:HIV / Q000187:drug effects*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry; D012995:Solubility; D014520:Urethane / Q000138:chemical synthesis
D000998:Antiviral Agents; D002254:Carbonates; D003853:Deoxyribonucleosides; D004987:Ethers; D011355:Prodrugs; D014520:Urethane