2-(ARYLALKYLAMINO)ADENOSIN-5'-URONAMIDES - A NEW CLASS OF HIGHLY SELECTIVE ADENOSINE-A2 RECEPTOR LIGANDS

被引：113

作者：

HUTCHISON, AJ ^{[1
]}

WILLIAMS, M ^{[1
]}

DEJESUS, R ^{[1
]}

YOKOYAMA, R ^{[1
]}

OEI, HH ^{[1
]}

GHAI, GR ^{[1
]}

WEBB, RL ^{[1
]}

ZOGANAS, HC ^{[1
]}

STONE, GA ^{[1
]}

JARVIS, MF ^{[1
]}

机构：

[1] CIBA GEIGY CORP,DEPT RES,DIV PHARMACEUT,SUMMIT,NJ 07901

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1990年 / 33卷 / 07期

关键词：

D O I：

10.1021/jm00169a015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The synthesis and receptor-binding profiles at adenosine receptor subtypes for a series of 2-(arylalkylamino)-adenosin-5'-uronamides is described, Halogenated 2-phenethylamino analogues such as 3e show greater than 200-fold selectivity for the A2 receptor subtype on the basis of rat brain receptor binding. The general structure-activity relationship of this series of compounds is discussed both in terms of potency at A2 receptors as well as receptor subtype selectivity. It is possible to introduce a hydrophilic carboxyalkyl substituent to this series such as in CGS 21680A (3h) and still retain good potency and selectivity for A2 receptors. In addition, functional data in a perfused working rat heart model shows that these compounds possess full agonist properties at A2receptors with 3h having a greater than 1500-fold separation between A2 (coronary vosadilatory) and A1 (negative chronotropic) receptor mediated events. © 1990, American Chemical Society. All rights reserved.

引用

页码：1919 / 1924

页数：6

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