Computer-assisted design, synthesis and biological evaluation of novel pyrrolyl heteroaryl sulfones targeted at HIV-1 reverse transcriptase as non-nucleoside inhibitors

Bioorg Med Chem. 2000 Sep;8(9):2305-9. doi: 10.1016/s0968-0896(00)00144-9.

Abstract

Three pyrrolyl heteroaryl sulfones (ethyl 1-[(1H-benzimidazol-2(3H)one-5-yl)sulfonyl]-1H-pyrrole-2-carboxyla te, ethyl 1-[(1H-benzimidazol-5(6)-yl)sulfonyl]-1H-pyrrole-2-carboxylate and ethyl 1-[(1H-benzotriazol-5(6)-yl)sulfonyl]-1H-pyrrole-2-carboxylate) were designed as novel HIV-1 reverse transcriptase non-nucleoside inhibitors using structure-based computational methods. Although these compounds were inactive in the cell-based assay, they inhibited the target enzyme with micromolar potency (IC50s = 2 microM, 3 microM and 9 microM, respectively).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Benzimidazoles / chemical synthesis
  • Benzimidazoles / pharmacology
  • Cell Division / drug effects
  • Cell Survival / drug effects
  • Computer-Aided Design
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • HIV-1 / drug effects
  • Inhibitory Concentration 50
  • Proline / analogs & derivatives*
  • Proline / chemical synthesis
  • Proline / pharmacology
  • RNA-Directed DNA Polymerase / drug effects*
  • Sulfones / chemical synthesis
  • Sulfones / pharmacology*

Substances

  • Anti-HIV Agents
  • Benzimidazoles
  • Enzyme Inhibitors
  • Sulfones
  • 2-pyrrolecarboxylic acid
  • Proline
  • RNA-Directed DNA Polymerase