Synthesis and Biological Evaluation of 2-Alkynyl-<i>N</i>⁶-methyl-5′-<i>N</i>-methylcarboxamidoadenosine Derivatives as Potent and Highly Selective Agonists for the Human Adenosine A₃Receptor

Abstract

A new series of 2-aralkynyl-N(6)-methyl-MECAs 10-13 were synthesized and evaluated in radioligand binding studies and in a new Eu-GTP functional assay that provides a powerful alternative to radioisotope use. The new compounds possess high affinity and selectivity for the AA(3)R with N(6)-methyl-2-phenylethynylMECA (10) showing a subnanomolar affinity and about 100000-fold selectivity vs AA(1)R and AA(2A)R. Furthermore, the new nucleosides showed to be full agonists, the N(6)-methyl-2-(2-pyridinyl)ethynylMECA (13) being the most potent in the series.