TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides
详细信息 查看全文
- 作者：Tae-Hwan Ha ; HyungChul Ryu ; Sung-Eun Kim ; Ho Shin Kim ; Jihyae Ann ; Phuong-Thao Tran ; Van-Hai Hoang ; Karam Son ; Minghua Cui ; Sun Choi ; Peter M. Blumberg ; Robert Frank ; Gregor Bahrenberg ; Klaus Schiene ; Thomas Christoph ; Sven Frormann ; Jeewoo Lee
- 关键词：TRPV1 antagonists ; Analgesic ; Capsaicin ; Resiniferatoxin
- 刊名：Bioorganic and Medicinal Chemistry
- 出版年：2013
- 出版时间：1 November, 2013
- 年：2013
- 卷：21
- 期：21
- 页码：6657-6664
- 全文大小：3391 K
文摘
A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode.