[摘要]：The adenosine receptor subfamily consists of the adenosine A1, A2A, A2B, and A3 receptors, which are localized in a variety of tissues throughout the human body. It is, therefore, a challenge to develop receptor specific ligands with improved tissue selectivity. Allosteric modulators could have these therapeutic advantages over orthosteric ligands. In the present study, a series of 2,4-disubstituted quinolines were synthesized on the basis of the structure of LUF6000. Compd. I (LUF6096) was able to allosterically enhance agonist binding to a similar extent as LUF6000. In addn., this new compd. showed low, if any, orthosteric affinity for any of the adenosine receptors. In a functional assay, I showed improved activity in comparison to LUF6000, as it increased both the intrinsic efficacy and the potency of the ref. agonist Cl-IB-MECA at the human adenosine A3 receptor.
