Synthesis and Biological Activity of New Potential Agonists for the Human Adenosine A2A Receptor

Autor:	J. Luis Diaz, Angel Guerrero, M. Pilar Bosch, Francisco Campos, Itziar Niubo, M. Isabel Loza, Gloria Rosell, José Brea
Rok vydání:	2004
Předmět:	Stereochemistry Chemistry Adenosine A2A receptor Biological activity Adenosine receptor Chemical synthesis Adenosine Radioligand Assay Drug Discovery medicine Molecular Medicine Structure–activity relationship Receptor medicine.drug
Zdroj:	Journal of Medicinal Chemistry. 47:4041-4053
ISSN:	1520-4804 0022-2623
DOI:	10.1021/jm031143+
Popis:	New adenosine derivatives have been synthesized and tested as putative agonists of adenosine receptors. Compounds 2−6 derive from the introduction of several types of substituents (electron donating, electron withdrawing, and halogens) in the para-position of the phenyl ring of the parent compound 1, and compound 7 lacks the hydroxyl group of amino alcohol 1. In radioligand binding assays using recombinant human A1, A2A, A2B, and A3 receptors, all compounds showed very low or negligible affinity for A1 and A2B receptors but compounds 3, 5, and 7 displayed a remarkably potent affinity for the A2A receptor with Ki values of 1−5 nM. Bromo derivative 3 displayed a selectivity A1/A2A = 62 and A3/A2A = 16 whereas the presence of a hydroxyl group (compound 5) improved the selectivity of A1/A2A and A3/A2A to 120- and 28-fold, respectively. When the methoxy derivative 4 lacks the hydroxyl group on the side chain (compound 7), the binding affinity for A2A is increased to 1 nM, improving selectivity ratios to 356- a...
Databáze:	OpenAIRE
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