3-and 6-Substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as A1 adenosine receptor allosteric modulators and antagonists

被引：34

作者：

Aurelio, Luigi ^{[3
]}

Valant, Celine ^{[1
,2
]}

Figler, Heidi ^{[4
,5
]}

Flynn, Bernard L. ^{[3
]}

Linden, Joel ^{[4
,5
]}

Sexton, Patrick M. ^{[1
,2
]}

Christopoulos, Arthur ^{[1
,2
]}

Scammells, Peter J. ^{[3
]}

机构：

[1] Monash Univ, Monash Inst Pharmaceut Sci, Drug Discovery Biol Lab, Clayton, Vic 3800, Australia

[2] Monash Univ, Dept Pharmacol, Clayton, Vic 3800, Australia

[3] Monash Univ, Monash Inst Pharmaceut Sci, Parkville, Vic 3052, Australia

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

[5] Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 20期

基金：

澳大利亚研究理事会; 美国国家卫生研究院; 英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;

关键词：

Allosteric modulator; A(1) adenosine receptor (A(1)AR); ADENOSINE-A1-RECEPTOR BINDING; AGONIST BINDING; ENHANCERS; 2-AMINO-3-BENZOYLTHIOPHENES;

D O I：

10.1016/j.bmc.2009.08.024

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：

A series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were prepared and evaluated as potential allosteric modulators at the A(1) adenosine receptor. The structure-activity relationships of the 3- and 6-positions of a series of 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines were explored. Despite finding that 3- and 6-substituted 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines possess the ability to recognize an allosteric site on the agonist-occupied A(1)AR at relatively high concentrations, the structural modifications we have performed on this scaffold favor the expression of orthosteric antagonist properties over allosteric properties. This research has identified 2-amino-4,5,6,7-tetrahydrothieno[2,3-c]pyridines as novel class of orthosteric antagonist of the A(1)AR and highlighted the close relationship between structural elements governing allosteric modulation and orthosteric antagonism of agonist function at the A(1)AR. (c) 2009 Elsevier Ltd. All rights reserved.

引用

页码：7353 / 7361

页数：9

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