Synthesis and adenosine receptors binding affinities of a series of 3-arylcoumarins

ObjectivesIn the present communication, we report the synthesis, pharmacological evaluation, theoretical evaluation of absorption, distribution, metabolism and excretion properties and structure-activity relationship study of a selected series of 3-arylcoumarins (compounds 1-9). Adenosine receptors (ARs) binding activity and selectivity of the synthesized compounds 1-9 were evaluated in this study. Different substituents were introduced in both benzene rings of the evaluated scaffold, at positions 6 and 3 or 4 of the moiety. The lack of data on the 3-arylcoumarin scaffold encouraged us to explore the ARs' binding activity of a selected series of derivatives. MethodsA new series of coumarins (compounds 1-9) were synthesized and evaluated by radioligand binding studies towards ARs. Key findingsAnalysing the experimental data, it can be observed that neither the simple 3-arylcoumarin nor the 4-nitro derivatives presented detectable binding affinity for the evaluated receptors, although most of the other substituted derivatives have good binding affinity profiles, especially against the hA(1)/hA(3) or only hA(3) AR. ConclusionsThe most remarkable derivative is compound 2, presenting the best affinity for hA(3) AR (K-i=2680 nM) and significant selectivity for this subtype.