Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved drug resistance properties. 2

J Med Chem. 2004 Nov 18;47(24):5923-36. doi: 10.1021/jm040072r.

Abstract

HIV-1 nonnucleoside reverse transcriptase inhibitors (NNRTIs) are part of the combination therapy currently used to treat HIV infection. The features of a new NNRTI drug for HIV treatment must include selective potent activity against both wild-type virus as well as against mutant virus that have been selected by use of current antiretroviral treatment regimens. Based on analogy with known HIV-1 NNRTI inhibitors and modeling studies utilizing the X-ray crystal structure of inhibitors bound in the HIV-1 RT, a series of substituted 2-quinolones was synthesized and evaluated as HIV-1 inhibitors.

MeSH terms

  • Alkynes
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Benzoxazines
  • Binding Sites
  • Cell Line
  • Crystallography, X-Ray
  • Cyclopropanes
  • Drug Design
  • Drug Resistance, Viral*
  • HIV Reverse Transcriptase / chemistry*
  • HIV Reverse Transcriptase / genetics
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects
  • HIV-1 / enzymology
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Mutation
  • Oxazines / chemistry
  • Quinolones / chemical synthesis*
  • Quinolones / chemistry
  • Quinolones / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Oxazines
  • Quinolones
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • efavirenz