1116652-17-5Relevant academic research and scientific papers
A series of 2,4-disubstituted quinolines as a new class of allosteric enhancers of the adenosine A3 receptor
Heitman, Laura H.,G?bly?s, Anikó,Zweemer, Annelien M.,Bakker, Renée,Mulder-Krieger, Thea,Van Veldhoven, Jacobus P. D.,De Vries, Henk,Brussee, Johannes,Ijzerman, Adriaan P.
supporting information; experimental part, p. 926 - 931 (2010/01/07)
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 (34). Compound 27 (LUF6096) was able to allosterically enhance agonist binding to a similar extent as 34. In addition, this new compound showed low, if any, orthosteric affinity for any of the adenosine receptors. In a functional assay, compound 27 showed improved activity in comparison to 34, as it increased both the intrinsic efficacy and the potency of the reference agonist Cl-IB-MECA at the human adenosine A 3 receptor.
