Truncated Reverse Isoxazolidinyl Nucleosides: A New Class of Allosteric HIV-1 Reverse Transcriptase Inhibitors

Affairs of the HAART! The synthesis of HEPT-derived, truncated reverse isoxazolidinyl nucleosides ( shown) is reported. These compounds represent the first examples of isoxazolidines bearing a pyrimidine scaffold at the C-3 position using a glycoside-type linkage. Biological evaluation showed that some of the derivatives act as non-nucleoside inhibitors of HIV-1 reverse transcriptase, with an efficacy comparable to that of Nevirapine but with reduced toxicity.