2-Aryl-2,2-difluoroacetamide FKBP12 ligands: synthesis and X-ray structural studies

Org Lett. 2001 Dec 13;3(25):3987-90. doi: 10.1021/ol0166909.

Abstract

[structure: see text] 2-Aryl-2,2-difluoroacetamido-proline and pipecolate esters are high affinity FKBP12 ligands whose rotamase inhibitory activity is comparable to that seen for the corresponding ketoamides. X-ray structural studies suggest that the fluorine atoms participate in discrete interactions with the Phe36 phenyl ring and the Tyr26 hydroxyl group, with the latter resembling a moderate-to-weak hydrogen bond.

MeSH terms

  • Acetamides / chemistry*
  • Animals
  • Binding Sites
  • Crystallography, X-Ray
  • Hydrocarbons, Fluorinated / chemical synthesis*
  • Hydrocarbons, Fluorinated / chemistry*
  • Hydrocarbons, Fluorinated / metabolism
  • Immunosuppressive Agents / chemistry
  • Immunosuppressive Agents / metabolism
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Protein Binding
  • Tacrolimus / chemistry*
  • Tacrolimus / metabolism
  • Tacrolimus Binding Protein 1A / chemistry*
  • Tacrolimus Binding Protein 1A / metabolism
  • Tacrolimus Binding Proteins / antagonists & inhibitors

Substances

  • Acetamides
  • Hydrocarbons, Fluorinated
  • Immunosuppressive Agents
  • Ligands
  • Tacrolimus Binding Protein 1A
  • Tacrolimus Binding Proteins
  • Tacrolimus