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

Rosaria Volpini; Michela Buccioni; Diego Dal Ben; Catia Lambertucci; Carmen Lammi; Gabriella Marucci; Anna T Ramadori; Karl-Norbert Klotz; Gloria Cristalli

doi:10.1021/jm900754g

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

J Med Chem. 2009 Dec 10;52(23):7897-900. doi: 10.1021/jm900754g.

Authors

Rosaria Volpini¹, Michela Buccioni, Diego Dal Ben, Catia Lambertucci, Carmen Lammi, Gabriella Marucci, Anna T Ramadori, Karl-Norbert Klotz, Gloria Cristalli

Affiliation

¹ Department of Chemical Sciences, University of Camerino, Via S Agostino 1, I-62032 Camerino, Italy.

PMID: 19839592
DOI: 10.1021/jm900754g

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine / analogs & derivatives
Adenosine / chemical synthesis*
Adenosine / pharmacology*
Adenosine A3 Receptor Agonists*
Animals
CHO Cells
Cricetinae
Cricetulus
Dose-Response Relationship, Drug
Fluorometry
Humans
Substrate Specificity

Substances

Adenosine A3 Receptor Agonists
Adenosine