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.
Luigi Aurelio  1 ,  Celine Valant ,  Bernard L Flynn ,  Patrick M Sexton ,  Arthur Christopoulos ,  Peter J Scammells
Affiliations
  • 1. Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
PMID: 19514747 DOI: 10.1021/jm9002582
Abstract

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.

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