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-br omophenyl 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 poten t 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 o f 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 furth er development of the dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT deriva tives as a new class of vaginal contraceptives capable of preventing the se xual transmission of HIV while providing fertility control for women who ar e at high risk of acquiring HIV by heterosexual transmission. These dual fu nction 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives may also have utility i n curbing domestic and wildlife animal retroviral transmissions.