| Abstract
| - 1H-Imidazo[4,5-c]quinolin-4-amine derivatives have been synthesized as allosteric modulators of the humanA3 adenosine receptor (AR). Structural modifications were made at the 4-amino and 2 positions. Thecompounds were tested in both binding and functional assays, and many were found to be allosteric enhancersof the action of A3AR agonists by several different criteria. First, a potentiation of the maximum efficacyof the agonist Cl-IB-MECA was observed for numerous derivatives. Also, a number of these compoundsdecreased the rate of dissociation of the agonist [125I]I-AB-MECA from the A3AR. Most prominently,compound 43 (LUF6000) was found to enhance agonist efficacy in a functional assay by 45% and decreasedissociation rate similarly without influencing agonist potency. The structural requirements for allostericenhancement at the A3AR were distinct from the requirements to inhibit equilibrium binding. Thus, wehave prepared allosteric enhancers of the human A3AR that have an improved allosteric effect in comparisonto the inhibition of equilibrium binding at the orthosteric site.
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