Synthesis and Biological Evaluation of 2-Alkynyl-N6-methyl-5′-N-methylcarboxamidoadenosine Derivatives as Potent and Highly Selective Agonists for the Human Adenosine A3 Receptor

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.