Allosteric modulators of the adenosine A1 receptor: synthesis and pharmacological evaluation of 4-substituted 2-amino-3-benzoylthiophenes

J Med Chem. 2009 Jul 23;52(14):4543-7. doi: 10.1021/jm9002582.


A series of 4-substituted 2-amino-3-benzoylthiophenes was screened using a functional assay of A(1)AR-mediated phosphorylation of ERK1/2 in intact CHO cells to identify both potential agonistic effects as well the ability to allosterically modulate the activity of the orthosteric agonist, R-PIA. More detailed concentration-response experiments were subsequently performed on two compounds (9a and 9o) utilizing both the ERK1/2 assay as well as a second assay of [(35)S]GTPgammaS binding to activated G proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / pharmacology
  • Adenosine A1 Receptor Agonists*
  • Adenosine A1 Receptor Antagonists*
  • Allosteric Regulation
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Phosphorylation / drug effects
  • Thiophenes / chemistry*
  • Thiophenes / pharmacology*


  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • Thiophenes
  • N-(1-methyl-2-phenylethyl)adenosine
  • Extracellular Signal-Regulated MAP Kinases
  • Adenosine