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.
Department of Chemical Sciences, University of Camerino, Via S Agostino 1, I-62032 Camerino, Italy.
Rosaria
R
Volpini
Michela
M
Buccioni
Diego
D
Dal Ben
Catia
C
Lambertucci
Carmen
C
Lammi
Gabriella
G
Marucci
Anna T
AT
Ramadori
Karl-Norbert
KN
Klotz
Gloria
G
Cristalli
D000241:Adenosine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D058909:Adenosine A3 Receptor Agonists; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005470:Fluorometry; D006801:Humans; D013379:Substrate Specificity
D058909:Adenosine A3 Receptor Agonists; D000241:Adenosine