SYNTHESIS AND ANTIRETROVIRAL EVALUATION OF NEW ALKOXY AND ARYLOXY PHOSPHATE DERIVATIVES OF 3'-AZIDO-3'-DEOXYTHYMIDINE

A series of new ether lipid-3'-azido-3'-deoxythymidine (AZT) conjugate s (11a-g) were synthesized and evaluated for anti-HIV activity. The ef fect of chirality on the antiviral activity was examined through the s ynthesis of AZT conjugates bearing alkoxypropanols in the lipid portio n of the molecule (11a-d). In addition, the long alkyl chain of alkoxy ethyl ether lipid-AZT analogs was replaced with aromatic groups (11e-g ), and the effect of this structural modification on activity is repor ted. The results of the biological tests indicate that analogs with a methyl group alpha to the phosphate moiety (11c,d) exhibit a marked de gree of stereoselectivity with regard to their anti-HIV activity. Also , replacement-of the long alkyl chain with aromatic groups in the oxya lkyl ether phospholipid-AZT conjugates leads to substantially more pot ent compounds (11e-g) with an anti-HIV activity comparable to that of AZT.