5-substituted 2-aminothiophenes as A1 adenosine receptor allosteric enhancers

被引：50

作者：

Aurelio, Luigi ^{[1
]}

Figler, Heidi ^{[2
]}

Flynn, Bernard L. ^{[1
]}

Linden, Joel ^{[2
]}

Scammells, Peter J. ^{[1
]}

机构：

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

[2] Univ Virginia, Dept Med & Pharmacol, Charlottesville, VA 22908 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 03期

关键词：

D O I：

10.1016/j.bmc.2007.10.065

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：

Two series of 5-substituted 2-amino-4-(3-trifluoromethylphenyl)thiophenes were prepared and evaluated as allosteric enhancers at the A(1) adenosine receptor (A(1)AR). In the 3-benzoyl series, a 5-phenyl group was found to confer the greatest potency (9a: ED50 = 2.1 mu M, AE score = 18%). However, the analogue with no 5-substituent (6b: ED50 = 15.8 mu M, AE score = 77%) proved to be the most efficacious. In the 3-ethoxycarbonyl series, the 5-(4-chlorophenyl) analogue was clearly the most potent and efficacious (91: ED50 = 6.6 mu M, AE score = 57%). The antagonist activity of all compounds was measured using a [H-3]CPX competitive binding assay. (c) 2007 Elsevier Ltd. All rights reserved.

引用

页码：1319 / 1327

页数：9

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