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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Line
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Cricetinae
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Humans
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Models, Molecular
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Purinergic P1 Receptor Antagonists*
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Pyrimidines / chemical synthesis*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology
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Receptor, Adenosine A3
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Receptors, Purinergic P1 / metabolism
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Solubility
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Structure-Activity Relationship
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Triazoles / chemical synthesis*
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Triazoles / chemistry
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Triazoles / pharmacology
Substances
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5-(((4-pyridyl)amino)carbonyl)amino-8-methyl-2-(2-furyl)pyrazolo(4,3-e)1,2,4-triazolo(1,5-c)pyrimdiine
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Purinergic P1 Receptor Antagonists
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Pyrimidines
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Receptor, Adenosine A3
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Receptors, Purinergic P1
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Triazoles