Abacavir prodrugs: microwave-assisted synthesis and their evaluation of anti-HIV activities.
The synthesis of a new series of abacavir prodrugs involving N2-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 microM and CC50 of >100 microM with selectivity index of >2000. Compound 3 was found to be 32 times more potent than the parent drug (EC50 of 1.6 microM). At pH 7.4, 37 degrees C, the hydrolytic t1/2 ranged between 120 and 240 min.
Sriram
Dharmarajan
D
Medicinal Chemistry Research Laboratory, Pharmacy Group, Birla Institute of Technology and Science, Pilani-333031, India. dsriram@bits-pilani.ac.in
Yogeeswari
Perumal
P
Myneedu
Naga Sirisha
NS
Saraswat
Vivek
V
D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001547:Benzaldehydes / Q000737:chemistry; D015224:Dideoxynucleosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D007659:Ketones / Q000737:chemistry; D008872:Microwaves; D011355:Prodrugs / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D013696:Temperature; D000099227:Abacavir
D019380:Anti-HIV Agents; D001547:Benzaldehydes; D015224:Dideoxynucleosides; D007659:Ketones; D011355:Prodrugs; D000099227:Abacavir