PYRIMIDINE THIOETHERS - A NOVEL CLASS OF HIV-1 REVERSE-TRANSCRIPTASE INHIBITORS WITH ACTIVITY AGAINST BHAP-RESISTANT HIV

A series of pyrimidine thioethers was synthesized and evaluated for in hibitory properties against wild-type HIV-1 reverse transcriptase (RT) and an RT carrying the resistance-conferring mutation P236L. Modifica tions of both the pyrimidine and the functionality attached through th e thioether yielded several analogues, which demonstrated activity aga inst both enzyme types, with IC50 values as low as 190 nM against wild -type and 66 nM against P236L RT. Evaluation of a select number of pyr imidine thioethers in cell culture showed that these compounds have ex cellent activity against HIV-1(IIIB)-WT and retain good activity again st a laboratory-derived HIV-1(MF) delavirdine-resistant variant.