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

• Published in: Bioorganic & medicinal chemistry letters 2010-11, Vol.20 (22), p.6592-6596
• Main Authors: Liu, Bin, Lee, Younghee, Zou, Jinming, Petrassi, H. Michael, Joseph, Rhoda W., Chao, Wenchun, Michelotti, Enrique L., Bukhtiyarova, Marina, Springman, Eric B., Dorsey, Bruce D.
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; Biological and medical sciences; Drug Discovery; Drug resistance; Enzymes; Human immunodeficiency virus 1; Medical sciences; Models, Molecular; NNRTIs; non-nucleoside reverse transcriptase inhibitors; Pharmacokinetics; Pharmacology. Drug treatments; Rats; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacokinetics; Reverse Transcriptase Inhibitors - pharmacology; SAR; Structure-Activity Relationship; Triazines - chemical synthesis; Triazines - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2010.09.034

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