Abstract
A new series of N6-methoxy-2-(ar)alkynyladenosine derivatives has
been synthesized and tested at the human recombinant adenosine receptors.
Binding studies demonstrated that the new compounds possess high
affinity and selectivity for the A3 subtype. Among them, compounds
bearing an N-methylcarboxamido substituent in the 4'-position showed
the highest A3 affinity and selectivity. In particular, the N6-methoxy-2-p-acetylphenylethynylMECA
(40; Ki A3 = 2.5 nM, A3 selectivity versus A1 = 21 500 and A2A =
4200) results in one of the most potent and selective agonists at
the human A3 adenosine receptor reported so far. Furthermore, functional
assay, performed with selected new compounds, revealed that the presence
of an alkylcarboxamido group in the 4'-position seems to be essential
to obtain full agonists at the A3 subtype. Finally, results of molecular
docking analysis were in agreement with binding and functional data
and could explain the high affinity and potency of the new compounds.
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