5-Substituted 2-aminothiophenes as A1 adenosine receptor allosteric enhancers Original Research Article

Two series of 5-substituted 2-amino-4-(3-trifluoromethylphenyl)thiophenes were prepared and evaluated as allosteric enhancers at the A1 adenosine receptor (A1AR). In the 3-benzoyl series, a 5-phenyl group was found to confer the greatest potency (9a: ED50 = 2.1 μM, AE score = 18%). However, the analogue with no 5-substituent (6b: ED50 = 15.8 μM, 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: ED50 = 6.6 μM, AE score = 57%). The antagonist activity of all compounds was measured using a [3H]CPX competitive binding assay.