5-Substituted 2-aminothiophenes as A1 adenosine receptor allosteric enhancers

Abstract Two series of 5-substituted 2-amino-4-(3-trifluoromethylphenyl)thiophenes were prepared and evaluated as allosteric enhancers at the A 1 adenosine receptor (A 1 AR). In the 3-benzoyl series, a 5-phenyl group was found to confer the greatest potency ( 9a : ED 50  = 2.1 μM, AE score = 18%). However, the analogue with no 5-substituent ( 6b : ED 50  = 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 : ED 50  = 6.6 μM, AE score = 57%). The antagonist activity of all compounds was measured using a [ 3 H]CPX competitive binding assay.