Synthesis of dual function (5R,6R)- and (5S,6S)-5-bromo-6-methoxy-5,6-dihydro-AZT-5′-(para-bromophenyl methoxyalaninyl phosphate) as novel spermicidal and anti-HIV agents

We synthesized a novel compound, 5-bromo-6-methoxy-5,6-dihydro-AZT-5'-(p-bromophenyl methoxyalaninyl phosphate), which had an EC50 value of 5 mu M in sperm motility assays. This is >1 log(10) better than that of the detergent spermicide nonoxynol-9 (EC50 81 mu M). The compound also displayed a potent anti-human immunodeficiency virus (HIV) activity with an IC50 value of 0.005 mu M in HIV replication assays, which was virtually identical to that of AZT (IC50 0.006 mu M) and >2 log(10) more potent than that of nonoxynol-9 (IC50 2.2 mu M). The promising results reported herein recommend the further development of the dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives as a new class of vaginal contraceptives capable of preventing the sexual transmission of HIV while providing fertility control for women who are at high risk of acquiring HIV by heterosexual transmission. These dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives may also have utility in curbing domestic and wildlife animal retroviral transmissions.