α-Substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues as potent and stereospecific TRPV1 antagonists

被引：28

作者：

Chung, Jae-Uk

Kim, Su Yeon

Lim, Ju-Ok

Choi, Hyun-Kyung

Kang, Sang-Uk

Yoon, Hae-Seok

Ryu, HyungChul

Kang, Dong Wook

Lee, Jeewoo ^{[1
]}

Kang, Bomi

Choi, Sun

Toth, Attila

Pearce, Larry V.

Pavlyukovets, Vladimir A.

Lundberg, Daniel J.

Blumberg, Peter M.

机构：

[1] Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea

[2] Ewha Womans Univ, Coll Pharm, Seoul 120750, South Korea

[3] Ewha Womans Univ, Natl Core Res Ctr Cell Signalling & Drug Discover, Seoul 120750, South Korea

[4] NIH, Natl Canc Inst, Canc Res Ctr, Lab Canc Biol & Genet, Bethesda, MD 20892 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2007年 / 15卷 / 18期

关键词：

TRPV1; antagonists; analgesic;

D O I：

10.1016/j.bmc.2007.06.041

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 alpha-Substituted N-(4-tert-butylbenzyl)-N'-[4-(methylsulfonylamino)benzyl]thiourea analogues have been investigated as TRPV1 receptor antagonists. alpha-Methyl substituted analogues showed potent and stereospecific antagonism to the action of capsaicin on rat TRPV1 heterologously expressed in Chinese hamster ovary cells. In particular, compounds 14 and 18, which possess the R-configuration, exhibited excellent potencies (respectively, K-i = 41 and 39.2 nM and K-i(ant) = 4.5 and 37 nM). (c) 2007 Published Elsevier Ltd.

引用

页码：6043 / 6053

页数：11

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