Biaryl ethers as novel non-nucleoside reverse transcriptase inhibitors with improved potency against key mutant viruses

J Med Chem. 2009 Nov 26;52(22):7163-9. doi: 10.1021/jm901230r.

Abstract

Biaryl ethers were recently reported as potent NNRTIs. Herein we disclose a detailed SAR study that led to the biaryl ether 6. This compound possessed excellent potency against WT RT and key clinically observed RT mutants and had an excellent pharmacokinetic profile in rats, dogs, and rhesus macaques. The compound also exhibited a clean safety profile in preclinical safety studies.

MeSH terms

  • Animals
  • Cell Line
  • Dogs
  • Ethers / chemical synthesis
  • Ethers / chemistry*
  • Ethers / pharmacokinetics
  • Ethers / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / genetics*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics*
  • Humans
  • Macaca mulatta
  • Mutation*
  • Nucleosides / chemistry
  • Rats
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacokinetics
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Ethers
  • Nucleosides
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase