title: 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.
authors.forename: Anna
authors.initials: A
authors.lastname: Maconi
authors.forename: Giorgia
authors.initials: G
authors.lastname: Pastorin
authors.forename: Tatiana
authors.initials: T
authors.lastname: Da Ros
authors.forename: Giampiero
authors.initials: G
authors.lastname: Spalluto
authors.forename: Zhan-Guo
authors.initials: ZG
authors.lastname: Gao
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Jacobson
authors.forename: Pier Giovanni
authors.initials: PG
authors.lastname: Baraldi
authors.forename: Barbara
authors.initials: B
authors.lastname: Cacciari
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Stefano
authors.initials: S
authors.lastname: Moro
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D006801:Humans; D008958:Models, Molecular; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D012995:Solubility; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C464661:5-(((4-pyridyl)amino)carbonyl)amino-8-methyl-2-(2-furyl)pyrazolo(4,3-e)1,2,4-triazolo(1,5-c)pyrimdiine; D058915:Purinergic P1 Receptor Antagonists; D011743:Pyrimidines; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D014230:Triazoles