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

Abstract

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 µM in sperm motility assays. This is >1 log₁₀ better than that of the detergent spermicide nonoxynol-9 (EC₅₀ 81 µM). The compound also displayed a potent anti-human immunodeficiency virus (HIV) activity with an IC₅₀ value of 0.005 µM in HIV replication assays, which was virtually identical to that of AZT (IC₅₀ 0.006 µM) and >2 log₁₀ more potent than that of nonoxynol-9 (IC₅₀ 2.2 µM). 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.