11 Feb

Aryl Phosphate Derivatives of Bromo-Methoxy-Azidothymidine: RESULTS(3)

The lead compound, WHI-07, with a p-bromo substitution (5-bromo-6-methoxy-5,6-dihydro-3′-azidothymidine-5′-(p-bromophenyl)-methoxyalaninyl phosphate), had an EC50 value of 6 ^M in sperm motility assays (Fig. 2), which is consistent with a one-log higher potency than that of the detergent spermicide N-9 (EC50 = 81 ^M). WHI-07 displayed a potent anti-HIV activity with an IC50 value of 0.005 ^M in HIV replication assays, which was virtually identical to that of AZT (IC50 = 0.006 ^M) and 439-fold more potent than that of N-9 (IC50 = 2.195 ^M) when tested side by side under identical experimental conditions (Fig. 2). canadian neighbor pharmacy

The removal of the azido group of the pentose ring (WHI-11 and WHI-12) was associated with a substantial loss of the anti-HIV activity and attenuation of the spermicidal activity for these novel dual-function AZT derivatives (Fig. 2). The 5-bromo-6-methoxy functional groups in the thymine ring appeared to be essential for the spermicidal activity of the p-methoxy-, p-fluoro-, or p-bromo-sub-stituted aryl phosphate derivatives of AZT, since no spermicidal activity was observed in their absence (i.e., the EC50 values for compounds WHI-08, WHI-09, and WHI-10 were all > 300 ^M) (Fig. 2). In contrast, the anti-HIV activity of the aryl phosphate derivatives of AZT did not require the bromo-methoxy functional groups in the thymine ring.

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