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

页码：7897 / 7900

页数：4

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