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

被引：36
|
作者：
Volpini, Rosaria [1 ]
Buccioni, Michela [1 ]
Dal Ben, Diev [1 ]
Lambertucci, Catia [1 ]
Lammi, Carmen [1 ]
Marucci, Gabriella [1 ]
Ramadori, Anna T. [1 ]
Klotz, Karl-Norbert [2 ]
Cristalli, Gloria [1 ]
机构：
[1] Univ Camerino, Dept Chem Sci, I-62032 Camerino, Italy
[2] Univ Wurzburg, Inst Pharmakol & Toxikol, D-97078 Wurzburg, Germany
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 23期
关键词：
2-ALKYNYL DERIVATIVES; ADENOSINE-5-N-ETHYLURONAMIDE; PHARMACOLOGY; LIGANDS;
D O I：
10.1021/jm900754g
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
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 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.
引用
收藏
页码：7897 / 7900
页数：4
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