Abacavir prodrugs: Microwave-assisted synthesis and their evaluation of anti-HIV activities

The synthesis of a new series of abacavir prodrugs involving N-2-substitution with various substituted benzaldehyde and ketone derivatives is described. The in vitro anti-HIV activities indicated that compound (3-(2-(4-methylaminobenzylideneamino)-6-(cyclopropylamino)-9H-purin-9-yl)cyclopentyl)methanol (3) was found to be most potent compound with EC50 of 0.05 mu M and CC50 of >100 mu M With selectivity index of >2000. Compound 3 was found to be 32 times more potent than the parent drug (EC50 of 1.6 mu M). At pH 7.4, 37 degrees C, the hydrolytic t(1/2) ranged between 120 and 240 min. (C) 2006 Elsevier Ltd. All rights reserved.