jm020974x_si_001.pdf (515.85 kB)
Synthesis, Biological Properties, and Molecular Modeling Investigation of the First Potent, Selective, and Water-Soluble Human A3 Adenosine Receptor Antagonist
journal contribution
posted on 2002-07-16, 00:00 authored by Anna Maconi, Giorgia Pastorin, Tatiana Da Ros, Giampiero Spalluto, Zhan-guo Gao, Kenneth A. Jacobson, Pier Giovanni Baraldi, Barbara Cacciari, Katia Varani, Stefano Moro, Pier Andrea BoreaA 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.