| Abstract
| - The Cambridge Structural Database (CSD) was searched through two 3D queries based onsubstructures shared by well-known antagonists at the A1 and A3 adenosine receptors (ARs).Among the resulting 557 hits found in the CSD, we selected five compounds to purchase,synthesize, or translate synthetically into analogues better tailored to interact with the biologicaltargets. Binding experiments using human ARs showed that four out of five tested compoundsturned out to be antagonists at the A1AR or A3AR with Ki values between 50 and 440 nM.Lead optimizations of 2-(benzimidazol-2-yl)quinoxalines (BIQs, 3) gave the best results in termsof potency and selectivity at the A1 and A3 ARs. Particularly, 2-(4-ethylthiobenzimidazol-2-yl)quinoxaline (3e) exhibited Ki values at the A1AR, A2AAR, and A3AR of 0.5, 3440, and 955nM, respectively, whereas 2-(4-methylbenzimidazol-2-yl)quinoxaline (3b) displayed at the sameARs Ki values of 8000, 833, and 26 nM, respectively.
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