N 6-[(Hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5′- N-ethylcarboxamido-adenosines: The first example of adenosine-related structures with potent agonist activity at the human A 2B adenosine receptor

Abstract

A new series of N 6-[(hetero)aryl/(cyclo)alkyl-carbamoyl-methoxy-phenyl]-(2-chloro)-5′- N-ethylcarboxamido-adenosines ( 24– 43) has been synthesised and tested in binding assays at hA 1, hA 2A and hA 3 adenosine receptors, and in a functional assay at the hA 2B subtype. The examined compounds displayed high potency in activating A 2B receptors with good selectivity versus A 2A subtypes. The introduction of an unsubstituted 4-[(phenylcarbamoyl)-methoxy]-phenyl chain at the N 6 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 (EC 50 hA 2B = 7.3 nM). These compounds represent the first report about adenosine-related structures capable of activating hA 2B subtype in the low nanomolar range.