Add time:07/13/2019         Source:sciencedirect.com

A new series of N6-[(hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5′-N-ethylcarboxamido-adenosines (24–43) has been synthesised and tested in binding assays at hA1, hA2A and hA3 adenosine receptors, and in a functional assay at the hA2B subtype. The examined compounds displayed high potency in activating A2B receptors with good selectivity versus A2A subtypes. The introduction of an unsubstituted 4-[(phenylcarbamoyl)-methoxy]-phenyl chain at the N6 position of 5′-N-ethylcarboxamido-adenosine led us to the recognition of compound 24 as a full agonist displaying the highest efficacy of the series (EC50 hA2B = 7.3 nM). These compounds represent the first report about adenosine-related structures capable of activating hA2B subtype in the low nanomolar range.

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