Synthesis and biological evaluation of allosteric A(1)-adenosine receptor modulators structurally related to (2-amino-4,5,6,7-tetrahydro-benzo[b]thiophen-3-yl)-(4-chloro-phenyl)-mie thanone, a potent compound useful to reduce neuropathic pain

New derivs. of (2-amino-4,5,6,7-tetrahydrobenzo[b]thiophen-3-yl)-(4-chlorophenyl)methanone (I), an allosteric enhancer of agonist binding to the A1-adenosine receptor, have been synthesized and evaluated in an intact cell assay at different concns. to det. which among them were potential allosteric enhancers of the action of adenosine to activate the human-A1 adenosine receptor. None of the synthesized compds. appear to be more potent than I at a concn. of 10 M. Most of the compds. increase the cAMP content of CHO cells expressing the human A1-adenosine receptor, indicating an antagonist activity. Only two of the evaluated compds. appeared to be allosteric enhancers at high concn. (10 M)