Discovery of triazolinone non-nucleoside inhibitors of HIV reverse transcriptase

Novel non-nucleoside inhibitors of HIV-RT that contain pyridazinone isosteres were prepared, and a series of triazolinones were found to be potent inhibitors of HIV replication. These compounds were active against several NNRTI-resistant virus strains. Pharmacokinetic studies indicated that inhibitor 7e has good bioavailability in rats. Several fragments of inhibitor 7c were prepared, and the binding of these compounds to HIV-RT was analyzed by surface plasmon resonance spectroscopy.

Novel diaryl ether HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) were prepared. Triazolinone compounds that strongly inhibit wild-type and NNRTI-resistant viruses and display excellent pharmacokinetic properties were identified.Figure optionsDownload as PowerPoint slide