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 2–20 nM range with negligible cytotoxicity and auspicious predicted pharmacological properties.

Graphical abstractSynthesis, assaying, and computational results are reported for new anti-HIV agents that exhibit high potency, low cytotoxicity, and promising pharmacological properties.Figure optionsDownload full-size imageDownload as PowerPoint slide