Synthesis and biological evaluation of 2-alkynyl-N~6-methyl- 5′-N-methylcarboxamidoadenosine derivatives as potent and highly selective agonists for the human adenosine A3 receptor

摘要

A new series of 2-aralkynyl-N~6-methyl-MECAs 10-13 were synthesized and evaluated in radioligand binding studies and in a newEu-GTP functional assay that provides a powerful alternative to radioisotope use. The new compounds possess high affinity and selectivity for the AA3R with N~6-methyl-2-phenylethynylMECA (10) showing a subnanomolar affinity and about 100000-fold selectivity vs AA_1R 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.