New pyrrolo[2,1-f]purine-2,4-dione and imidazo[2,1-f]purine-2,4-dione derivatives as potent and selective human A3 adenosine receptor antagonists

被引：44

作者：

Baraldi, PG ^{[1
]}

Preti, D

Tabrizi, MA

Fruttarolo, F

Romagnoli, R

Zaid, NA

Moorman, AR

Merighi, S

Varani, K

Borea, PA

机构：

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

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

[3] King Pharmaceut R&D, Cary, NC 27513 USA

[4] An Najah Natl Univ, Coll Pharm, Nablus, Palestine, Israel

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 14期

关键词：

D O I：

10.1021/jm058008c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Compounds presenting an additional fused ring on the xanthine nucleus have been reported to exhibit antagonistic activity with various levels of affinity and selectivity toward the four adenosine receptors subtypes A(1) A(2A), A(2B), and A(3). This paper reports synthesis and biological evaluation of new 1-benzyl-3-propyl-IH,6H-pyrrolo[2,1-f]purine-2,4-diones and 1-benzyl-3propyl- 1H,8H-imidazo [2, 1-f] purine-2,4-diones, among which we identified potent and selective A(3) adenosine receptors antagonists. In particular, 1-benzyl-7-methyl-3-propyl-IH,8H-imidazo[2,1-f]purine-2,4-dione (11e) shows a K-i (hA(3)) value from binding assay of 0.8 nM.

引用

页码：4697 / 4701

页数：5