5-Substituted 2-aminothiophenes as A1 adenosine receptor allosteric enhancers

Bioorg Med Chem. 2008 Feb 1;16(3):1319-27. doi: 10.1016/j.bmc.2007.10.065. Epub 2007 Oct 23.


Two series of 5-substituted 2-amino-4-(3-trifluoromethylphenyl)thiophenes were prepared and evaluated as allosteric enhancers at the A(1) adenosine receptor (A(1)AR). In the 3-benzoyl series, a 5-phenyl group was found to confer the greatest potency (9a: ED(50)=2.1 microM, AE score=18%). However, the analogue with no 5-substituent (6b: ED(50)=15.8 microM, AE score=77%) proved to be the most efficacious. In the 3-ethoxycarbonyl series, the 5-(4-chlorophenyl) analogue was clearly the most potent and efficacious (9l: ED(50)=6.6 microM, AE score=57%). The antagonist activity of all compounds was measured using a [(3)H]CPX competitive binding assay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A1 Receptor Antagonists*
  • Allosteric Regulation
  • Amination
  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry*
  • Aniline Compounds / pharmacology*
  • Animals
  • CHO Cells
  • Carboxylic Acids / chemical synthesis
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / pharmacology
  • Cricetinae
  • Cricetulus
  • Humans
  • Molecular Structure
  • Receptor, Adenosine A1 / metabolism
  • Structure-Activity Relationship


  • Adenosine A1 Receptor Antagonists
  • Aniline Compounds
  • Carboxylic Acids
  • Receptor, Adenosine A1
  • 2-aminothiophenol