Novel nevirapine-like inhibitors with improved activity against NNRTI-resistant HIV: 8-heteroarylthiomethyldipyridodiazepinone derivatives

Bioorg Med Chem Lett. 2004 Feb 9;14(3):739-42. doi: 10.1016/j.bmcl.2003.11.049.

Abstract

A series of 8-heteroarylthiomethyldipyridodiazepinone derivatives were prepared and evaluated for their antiviral profile against wild type virus and the important K103N/Y181C mutant as an indicator for broad activity. 2,6-Dimethylpyridine derivative 16 was found to have a good pharmacokinetic profile in spite of poor metabolic stability in rat liver microsomes.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Anti-HIV Agents* / chemical synthesis
  • Anti-HIV Agents* / metabolism
  • Anti-HIV Agents* / pharmacology
  • Azepines* / chemical synthesis
  • Azepines* / metabolism
  • Azepines* / pharmacology
  • Drug Resistance, Viral
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Reverse Transcriptase / chemistry
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Humans
  • Metabolic Clearance Rate
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Mutation
  • Nevirapine / chemical synthesis*
  • Nevirapine / pharmacology
  • Pyridines / chemical synthesis
  • Pyridines / metabolism
  • Pyridines / pharmacology
  • Rats
  • Reverse Transcriptase Inhibitors* / chemical synthesis
  • Reverse Transcriptase Inhibitors* / metabolism
  • Reverse Transcriptase Inhibitors* / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Azepines
  • Pyridines
  • Reverse Transcriptase Inhibitors
  • Nevirapine
  • HIV Reverse Transcriptase
  • pyridine