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Nevertheless, these compounds constitute the major class of antiviral drugs,andthis approach is likely to yield additional active compounds in the near future. Forthe long term, however, other strategies may ultimately lead tumor selectiveagent within lower toxicity.Obviously, the key to design analogue with a lower affinity for the hostenzyme than the viral enzyme, which requires that there be structural differencesbetween the enzyme active sites. For reverse transcriptase, the most wellstudied inhibitor is 3’-azido-3’-deoxythymidine (AZT; 32), which is currentlyused clinically to treat AIDS. 285,286OHNCH 3HOO NON 3(32)3’-azido-3’-deoxythymidine (AZT) inhibits HIV reverse transcriptase withan IC50 of 40nM 287 , but is 100-300 times less active against mammalian DNApolymerase and DNA polymerase . The reason for this selectivity is not clearsince 3’-azido-3’-deoxythymidine (AZT) is a chain terminator for mammalianDNA polymerases and inhibits normal cellular DNA synthesis .288 Several otherdideoxy nucleoside analogs have been shown to be potent inhibitors of HIVreplication in vitro. 289,290 In general, these compounds have the samemechanism of action as 3’-azido- 3’-deoxythymidine (AZT), that is, intracellular59Pyrimidine…..