Synthesis of hypermodified adenosine derivatives as selective adenosine A3 receptor ligands

被引：11

作者：

Cosyn, L

Gao, ZG

Van Rompaey, P

Lu, CR

Jacobson, KA

Van Calenbergh, S

机构：

[1] NIDDKD, Mol Recognit Sect,LBC, Bioorgan Chem Lab,NIDDK, DHHS,NIH, Bethesda, MD 20892 USA

[2] Univ Ghent, Lab Med Chem FFW, B-9000 Ghent, Belgium

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2006年 / 14卷 / 05期

关键词：

adenosine A(3) receptor; selectivity; affinity; ribose and purine modifications;

D O I：

10.1016/j.bmc.2005.09.062

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We investigated the A(3)AR affinity and selectivity of a series of 2-substituted 3'-azido and 3'-amino adenosine derivatives as well as some 5-uronamide derivatives thereof. All compounds showed high A3AR selectivity. While the 3'-azides appeared to be A3AR antagonists with moderate A3AR affinity, their 3'-amino congeners exhibit significantly improved A3AR affinity and behave as partial agonists. For both the 3'-azides and the 3'-amines, the 5'-methylcarbamoyl modification improved the overall affinity. Introduction of a 2-phenylethynyl substituent provided high affinity for the A3AR. (c) 2005 Elsevier Ltd. All rights reserved.

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页码：1403 / 1412

页数：10

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