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

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: ED50 = 2.1 mu M, AE score = 18%). However, the analogue with no 5-substituent (6b: ED50 = 15.8 mu M, 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 (91: ED50 = 6.6 mu M, AE score = 57%). The antagonist activity of all compounds was measured using a [H-3]CPX competitive binding assay. (c) 2007 Elsevier Ltd. All rights reserved.