Dual acting antioxidant A1 adenosine receptor agonists

被引：19

作者：

Gregg, Alison

Bottle, Steven E.

Devine, Shane M.

Figler, Heidi

Linden, Joel

White, Paul

Pouton, Colin W.

Urmaliya, Vijay

Scammells, Peter J.

机构：

[1] Monash Univ, Victorian Coll Pharm, Dept Med Chem, Parkville, Vic 3052, Australia

[2] Queensland Univ Technol, Sch Phys Sci & Chem Sci, Brisbane, Qld 4001, Australia

[3] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA

[4] Monash Univ, Victorian Coll Pharm, Dept Pharmaceut Biol, Parkville, Vic 3052, Australia

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2007年 / 17卷 / 19期

关键词：

adenosine; antioxidant; A(1) adenosine receptor (A(1)AR) agonist;

D O I：

10.1016/j.bmcl.2007.07.035

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Herein we report the synthesis and biological evaluation of some potent and selective A, adenosine receptor agonists, which incorporate a functionalised linker attached to an antioxidant moiety. N-6-(2,2,5,5-Tetramethylpyrrolidin-1-yloxyl-3-ylmethyl)-adenosine (VCP28, 2e) proved to be an agonist with high affinity (K-i = 50 nM) and good selectivity (A(3)/A(1) >= 400) for the A, adenosine receptor. N-6-[4-[2-[1,1,3,3-Tetramethylisoindolin-2-yloxyl-5-amido]ethyl]phenyl]adenosine (VCP102, 5a) has higher binding affinity (Ki = 7 nM), but lower selectivity (A(3)/A(1) = similar to 3). All compounds bind weakly (K-i > 1 mu M) to A(2A) and A(2B) receptors. The combination of-A, agonist activity and antioxidant activity has the potential to produce cardioprotective effects. (C) 2007 Elsevier Ltd. All rights reserved.

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收藏

页码：5437 / 5441

页数：5

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