Allosteric Modulators of the Adenosine A1 Receptor: Synthesis and Pharmacological Evaluation of 4-Substituted 2-Amino-3-benzoylthiophenes

被引：117

作者：

Aurelio, Luigi ^{[1
]}

Valant, Celine ^{[1
,2
,3
]}

Flynn, Bernard L. ^{[1
]}

Sexton, Patrick M. ^{[1
,2
,3
]}

Christopoulos, Arthur ^{[1
,2
,3
]}

Scammells, Peter J. ^{[1
]}

机构：

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

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

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 14期

关键词：

ADENOSINE-A1-RECEPTOR BINDING; BIOLOGICAL EVALUATION; AGONIST BINDING; ENHANCERS; 2-AMINOTHIOPHENES; KETONES;

D O I：

10.1021/jm9002582

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of 4-substituted 2-amino-3-benzoylthiophenes was screened using a functional assay of A A(1)AR-mediated phosphorylation of ERK 1/2 in intact CHO cells to identify both potential agonistic effects as well the ability to allosterically modulate the activity of the orthosteric agonist, R-PIA. More detailed concentration-response experiments were subsequently performed on two compounds (9a and 9o) utilizing both the ERK 1/2 assay as well as a second assay of [S-35]GTP gamma S binding to activated G proteins.

引用

页码：4543 / 4547

页数：5

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