Synthesis, adenosine receptor binding and 3D-QSAR of 4-substituted 2-(2′-furyl)-1,2,4-triazolo[1,5-a]quinoxalines

A collection of 25 2-(2′-furyl)-1,2,4-triazolo[1,5-a]quinoxalines incorporating different substitution patterns at position 4 have been synthesized and their binding affinity towards human adenosine receptors (hA1, hA2A, hA2B and hA3) was determinated. The biological data show that several potent at hA1, but lightly selective, adenosine ligands were identified. Moreover, these results confirmed the hypothesis that the structural modifications carried out on the 4-position of the tricyclic system produces a remarkable modification of the adenosine receptorial profile. A 3D-QSAR modelling study (GRIND/ALMOND methodology) performed on the hA1 data gave further support to the pharmacological results, and it is presented as a useful tool for the future design of ligands with better pharmacological profiles.

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