Synthesis and Biological Evaluation of 2-Amino-3-(4-Chlorobenzoyl)-4-[N-(Substituted) Piperazin-1-yl]Thiophenes as Potent Allosteric Enhancers of the A1 Adenosine Receptor

Abstract

The synthesis and evaluation of a series of 2-amino-3-(4-chlorobenzoyl)-4-[4-(alkyl/aryl)piperazin-yl]thiophene derivatives as allosteric enhancers of the A 1-adenosine receptor are described. The nature of substituents on the phenyl ring tethered to the piperazine seem to exert a fundamental influence on the allosteric enhancer activity, with the 4-chlorophenyl 8f and 4-trifluoromethyl 8j derivatives being the most active compounds in binding (saturation and displacement experiments) and functional cAMP studies.