Discovery and SAR of a series of 4,6-diamino-1,3,5-triazin-2-ol as novel non-nucleoside reverse transcriptase inhibitors of HIV-1

The discovery and SAR study of a series of 4,6-diamino-1,3,5-triazin-2-ol compounds as novel HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) are reported. The lead compounds in this series showed excellent activity against wild-type and drug-resistant RT enzymes and viral strains. In addition, compounds from this series demonstrated favorable pharmacokinetic profile in rat. A preliminary modeling study was conducted to understand the binding mode of this series of compounds. (C) 2010 Elsevier Ltd. All rights reserved.