Synthesis, biological properties, and molecular modeling investigation of the first potent, selective, and water-soluble human A3 adenosine receptor antagonist

被引：64

作者：

Maconi, A

Pastorin, G

Da Ros, T

Spalluto, G

Gao, ZG

Jacobson, KA

Baraldi, PG

Cacciari, B

Varani, K

Moro, S

Borea, PA

机构：

[1] Univ Trieste, Dipartimento Sci Farmaceut, I-34127 Trieste, Italy

[2] NIDDKD, NIH, Mol Recognit Sect, LBC, Bethesda, MD 20892 USA

[3] Univ Ferrara, Dipartimento Sci Farmaceut, I-44100 Ferrara, Italy

[4] Univ Ferrara, Dipartimento Med Clin & Sperimentale, Sez Farmacol, I-44100 Ferrara, Italy

[5] Univ Padua, Dipartimento Sci Farmaceut, Mol Modeling Sect, I-35131 Padua, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2002年 / 45卷 / 17期

关键词：

D O I：

10.1021/jm020974x

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：3579 / 3582

页数：4

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