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

Bin Liu; Younghee Lee; Jinming Zou; H Michael Petrassi; Rhoda W Joseph; Wenchun Chao; Enrique L Michelotti; Marina Bukhtiyarova; Eric B Springman; Bruce D Dorsey

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 of HIV-1

Bioorg Med Chem Lett. 2010 Nov 15;20(22):6592-6. doi: 10.1016/j.bmcl.2010.09.034. Epub 2010 Sep 21.

Authors

Bin Liu¹, Younghee Lee, Jinming Zou, H Michael Petrassi, Rhoda W Joseph, Wenchun Chao, Enrique L Michelotti, Marina Bukhtiyarova, Eric B Springman, Bruce D Dorsey

Affiliation

¹ Ansaris, Four Valley Square, 512 E. Township Line Rd, Blue Bell, PA 19422, United States. [email protected]

PMID: 20888224
DOI: 10.1016/j.bmcl.2010.09.034

Abstract

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.

MeSH terms

Animals
Drug Discovery*
Models, Molecular
Rats
Reverse Transcriptase Inhibitors / chemistry*
Reverse Transcriptase Inhibitors / pharmacokinetics
Reverse Transcriptase Inhibitors / pharmacology*
Structure-Activity Relationship
Triazines / chemical synthesis*
Triazines / pharmacology*

Substances

Reverse Transcriptase Inhibitors
Triazines