ACTION OF URACIL ANALOGS ON HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 AND ITS REVERSE-TRANSCRIPTASE

Three structural analogs of 5-ethyl-1-benzyloxymethyl-6-(phenylthio) ( E-BPU) inhibited human immunodeficiency virus type 1 (HIV-1) replicati on without cytotoxicity in vitro and were more potent than azidothymid ine and were as potent as E-BPU, The target of these compounds is HIV- 1 reverse transcriptase. Reverse transcriptases resistant to nevirapin e (tyrosine at position 181 to cysteine) and TIBO R82150 (leucine at p osition 100 to isoleucine) are cross resistant to E-BPU analogs. Nevir apine- or TIBO R82150-resistant HIV-1 were cross resistant to E-BPU an alogs but were inhibited at concentrations 11- to 135-fold lower than the cytotoxic doses.