Structure-activity relationships of new 1H-imidazo[4,5-c]quinolin-4-amine derivatives as allosteric enhancers of the A3 adenosine receptor.

ABSTRACT: 1H-Imidazo[4,5-c]quinolin-4-amine derivatives have been synthesized as allosteric modulators of the human A3 adenosine receptor (AR). Structural modifications were made at the 4-amino and 2 positions. The compounds were tested in both binding and functional assays, and many were found to be allosteric enhancers of the action of A3AR agonists by several different criteria. First, a potentiation of the maximum efficacy of the agonist Cl-IB-MECA was observed for numerous derivatives. Also, a number of these compounds decreased 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 decrease dissociation rate similarly without influencing agonist potency. The structural

SUBMITTER: Goblyos A 

PROVIDER: S-EPMC2547348 | biostudies-literature | 2006 Jun

REPOSITORIES: biostudies-literature