Optimization of pyrimidinyl- and triazinyl-amines as non-nucleoside inhibitors of HIV-1 reverse transcriptase

Non-nucleoside inhibitors of HIV-1 reverse transcriptase are being pursued through synthesis and assaying for anti-viral activity. Following computational analyses, the focus has been on the motif Het–NH–Ph–U, where Het is an aromatic heterocycle and U is an unsaturated, hydrophobic group. Previous investigations with Het=2-thiazoyl and 2-pyrimidinyl are extended here to triazinyl derivatives. The result is several NNRTIs in the 2–20nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.