8-POLYCYCLOALKYL-1,3-DIPROPYLXANTHINES AS POTENT AND SELECTIVE ANTAGONISTS FOR ADENOSINE-A1-RECEPTORS

被引：83

作者：

SHIMADA, J ^{[1
]}

SUZUKI, F ^{[1
]}

NONAKA, H ^{[1
]}

ISHII, A ^{[1
]}

机构：

[1] KYOWA HAKKO KOGYO CO LTD,PHARMACEUT RES LABS,1188 SHIMOTOGARI,NAGAIZUMI,SHIZUOKA 411,JAPAN

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 05期

关键词：

D O I：

10.1021/jm00083a018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

With the aim of characterizing the hydrophobic interactions between xanthines and the A1 receptor site, 1,3-dipropyl-8-substituted xanthines were synthesized. Introduction of a quaternary carbon and the conformationally restricted cyclopentyl moiety into the 8-position of xanthines enhanced the adenosine A1 antagonism. 1,3-Dipropyl-8-(3-noradamantyl)xanthine (42) was identified to be a selective and the most potent A1 receptor antagonist reported to date. Under our structure-activity relationship, the 8-substituent of xanthine antagonists and the N6-substituent of adenosine agonists appears to bind to the same region of the A1 receptor.

引用

页码：924 / 930

页数：7

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