Synthesis and biological evaluation of 2-aminothiazoles and their amide derivatives on human adenosine receptors. Lack of effect of 2-aminothiazoles as allosteric enhancers.

Abstract A number of 2-aminothiazoles ( 2a – e ) and their amide derivatives ( 4 – 10 ) were prepared. The 2-aminothiazoles themselves were tested as allosteric enhancers of agonist binding to human adenosine A 1 receptors. In a variety of experimental set-ups the compounds did not show any such effect, in contrast to earlier findings by another research group. Subsequently the 2-aminothiazoles were used as intermediates in the synthesis of a number of amide derivatives of either aromatic ( 4 – 6 ) or aliphatic nature ( 7 – 10 ). Some of the compounds emerged as moderately active antagonists on human adenosine A 1 and/or A 2A receptors with lower or negligible potency at adenosine A 3 receptors.