Allosteric Modulators of the Adenosine A₁Receptor: Synthesis and Pharmacological Evaluation of 4-Substituted 2-Amino-3-benzoylthiophenes

Abstract

A series of 4-substituted 2-amino-3-benzoylthiophenes was screened using a functional assay of A1AR-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 [35S]GTPγS binding to activated G proteins.