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Synthesis, biological properties, and molecular modeling investigation of the first potent, selective, and water-soluble human A(3) adenosine receptor antagonist.

Abstract：

:A new, highly potent, selective, and water-soluble antagonist of the hA(3) adenosine receptor was synthesized and tested in binding and functional assays. Compound 4 (5-[[(4-pyridyl)amino]carbonyl]amino-8-methyl-2-(2-furyl)-pyrazolo[4,3-e]1,2,4-triazolo[1,5-c]pyrimidine hydrochloride) displayed high water solubility (15 mM) and the highest affinity (K(i) = 0.01 nM) and selectivity for the hA(3) versus A(1), A(2A), and A(2B) receptors (>10000-fold) ever reported. A Schild analysis of the antagonism by 4 of agonist-induced inhibition of cAMP production in CHO cells expressing the hA(3) receptor indicated a K(B) value of 0.20 nM.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Maconi A,Pastorin G,Da Ros T,Spalluto G,Gao ZG,Jacobson KA,Baraldi PG,Cacciari B,Varani K,Moro S,Borea PA

doi

10.1021/jm020974x

keywords:

subject

Has Abstract

pub_date

2002-08-15 00:00:00

pages

3579-82

issue

17

eissn

0022-2623

issn

1520-4804

pii

jm020974x

journal_volume

45

pub_type

杂志文章

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