A new, highly potent, selective, and water-soluble antagonist of the hA3 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 (Ki ) 0.01 nM) and selectivity for the hA3 versus A1, A2A, and A2B 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 hA3 receptor indicated a KB value of 0.20 nM.
Synthesis, Biological properties and molecular modeling investigation of the first potent, selective and water soluble human A3 adenosine receptor antagonist
DA ROS, TATIANA;SPALLUTO, GIAMPIERO;
2002-01-01
Abstract
A new, highly potent, selective, and water-soluble antagonist of the hA3 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 (Ki ) 0.01 nM) and selectivity for the hA3 versus A1, A2A, and A2B 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 hA3 receptor indicated a KB value of 0.20 nM.File in questo prodotto:
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