Synthesis and biological evaluation of 2-amino-3-(4-chlorobenzoyl)-4-[N-(substituted) piperazin-1-yl]thiophenes as potent allosteric enhancers of the A1 adenosine receptor

J Med Chem. 2008 Sep 25;51(18):5875-9. doi: 10.1021/jm800586p. Epub 2008 Aug 26.


The synthesis and evaluation of a series of 2-amino-3-(4-chlorobenzoyl)-4-[4-(alkyl/aryl)piperazin-yl]thiophene derivatives as allosteric enhancers of the A 1-adenosine receptor are described. The nature of substituents on the phenyl ring tethered to the piperazine seem to exert a fundamental influence on the allosteric enhancer activity, with the 4-chlorophenyl 8f and 4-trifluoromethyl 8j derivatives being the most active compounds in binding (saturation and displacement experiments) and functional cAMP studies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine A1 Receptor Agonists*
  • Allosteric Regulation
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Thiophenes / chemical synthesis*
  • Thiophenes / pharmacology*


  • Adenosine A1 Receptor Agonists
  • Thiophenes