Synthesis, Structure-Activity Relationship, and Pharmacological Profile of Analogs of The ASIC-3 Inhibitor A-317567

被引：28

作者：

Kuduk, Scott D. ^{[1
]}

Di Marco, Christina N. ^{[1
]}

Bodmer-Narkevitch, Vera ^{[1
]}

Cook, Sean P. ^{[2
]}

Cato, Matthew J. ^{[2
]}

Jovanovska, Aneta ^{[2
]}

Urban, Mark O. ^{[2
]}

Leitl, Michael ^{[2
]}

Sain, Nova ^{[2
]}

Liang, Annie ^{[2
]}

Spencer, Robert H. ^{[2
]}

Kane, Stefanie A. ^{[2
]}

Hartman, George D. ^{[1
]}

Bilodeau, Mark T. ^{[1
]}

机构：

[1] Merck Res Labs, Dept Med Chem, West Point, PA 19486 USA

[2] Merck Res Labs, Dept Pain Res, West Point, PA 19486 USA

来源：

ACS CHEMICAL NEUROSCIENCE | 2010年 / 1卷 / 01期

关键词：

Pain; acid-sensing; ion channel; ASIC-3; degenerin; SENSING ION CHANNELS; ACID SENSORS; AMILORIDE; PAIN; ANTINOCICEPTION; BEHAVIOR; RECEPTOR; AMYGDALA; SUBUNIT; MICE;

D O I：

10.1021/cn9000186

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：

The synthesis, structure activity relationship (SA R), and pharmacological evaluation of analogs of the acid-sensing ion channel (ASIC) inhibitor A-317567 are reported. It was found that the compound with an acetylenic linkage was the most potent ASIC-3 channel blocker. This compound reversed mechanical hypersensitivity in the rat iodoacetate model of osteoarthritis pain, although sedation was noted. Sedation was also observed in ASIC-3 knockout mice, questioning whether sedation and antinociception are mediated via a non-ASIC-3 specific mechanism.

引用

页码：19 / 24

页数：6

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