Design, synthesis, anti-HIV evaluation and molecular modeling of piperidine-linked amino-triazine derivatives as potent non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem. 2012 Jun 15;20(12):3856-64. doi: 10.1016/j.bmc.2012.04.030. Epub 2012 Apr 21.

Abstract

A novel series of piperidine-linked amino-triazine derivatives were designed, synthesized and evaluated for in vitro anti-HIV activity as non-nucleoside reverse transcriptase inhibitors on the basis of our previous work. Screening results indicated that most compounds showed excellent activity against wild-type HIV-1 with EC(50) values in low nanomolar concentration range (especially compound 6b3, EC(50) = 4.61 nM, SI = 5945) and high activity against K103N/Y181C resistant mutant strain of HIV-1 with EC(50) values in low micromolar concentration range. In addition, preliminary structure-activity relationship and molecular modeling of these new analogs were detailed in this manuscript.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amines / chemistry
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology*
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Design*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-2 / drug effects*
  • Humans
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Molecular Structure
  • Piperidines / chemistry
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Triazines / chemistry

Substances

  • Amines
  • Anti-HIV Agents
  • Piperidines
  • Reverse Transcriptase Inhibitors
  • Triazines
  • piperidine
  • HIV Reverse Transcriptase