The design and synthesis of diaryl ether second generation HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs) with enhanced potency versus key clinical mutations

Bioorg Med Chem Lett. 2008 May 1;18(9):2959-66. doi: 10.1016/j.bmcl.2008.03.064. Epub 2008 Mar 25.

Abstract

Using a combination of traditional Medicinal Chemistry/SAR analysis, crystallography, and molecular modeling, we have designed and synthesized a series of novel, highly potent NNRTIs that possess broad antiviral activity against a number of key clinical mutations.

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / pharmacology*
  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design*
  • Drug Resistance, Viral
  • Ethers / chemistry*
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / genetics
  • Models, Chemical
  • Mutation
  • Nucleosides / chemistry
  • Reverse Transcriptase Inhibitors / chemical synthesis
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship
  • Virus Replication / drug effects*
  • Virus Replication / physiology

Substances

  • Anti-HIV Agents
  • Ethers
  • Nucleosides
  • Reverse Transcriptase Inhibitors

Associated data

  • PDB/3C6U