2-Phenylhydroxypropynyladenosine derivatives as high potent agonists at A2B adenosine receptor subtype

Adenosine derivatives bearing in 2-position the (R,S)-phenylhydroxypropynyl chain were evaluated for their potency at human A2B adenosine receptor, stably transfected on CHO cells, on the basis that (R,S)-2-phenylhydroxy-propynyl-5'-N-ethylcarboxyamidoadenosine [(R,S)-PHPNECA] was found to be a good agonist at the A2B receptor subtype. Biological studies demonstrated that the presence of small alkyl groups in N6-position of these molecules are well tolerated, whereas large groups abolished A2B potency. On the other hand, the presence of an ethyl group in the 4'-carboxamido function seems to be optimal, the (S)-PHPNECA resulting the most potent agonist at A2B receptor reported so far.