N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region

被引：12

作者：

Kim, Yong Soo ^{[1
]}

Kil, Min-Jung ^{[1
]}

Kang, Sang-Uk ^{[1
]}

Ryu, HyungChul ^{[1
]}

Kim, Myeong Seop ^{[1
]}

Cho, Yongsung ^{[1
]}

Bhondwe, Rahul S. ^{[1
]}

Thorat, Shivaji A. ^{[1
]}

Sun, Wei ^{[2
]}

Liu, Keliang ^{[2
]}

Lee, Jin Hee ^{[3
,4
]}

Choi, Sun ^{[3
,4
]}

Pearce, Larry V. ^{[5
]}

Pavlyukovets, Vladimir A. ^{[5
]}

Morgan, Matthew A. ^{[5
]}

Tran, Richard ^{[5
]}

Lazar, Jozsef ^{[5
]}

Blumberg, Peter M. ^{[5
]}

Lee, Jeewoo ^{[1
]}

机构：

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

[2] Shenyang Pharmaceut Univ, Shenyang 110016, Liaoning, Peoples R China

[3] Ewha Womans Univ, Div Life & Pharmaceut Sci, Coll Pharm, Seoul 120750, South Korea

[4] Ewha Womans Univ, Natl Core Res Ctr Cell Signaling & Drug Discovery, Seoul 120750, South Korea

[5] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2012年 / 20卷 / 01期

基金：

美国国家卫生研究院; 新加坡国家研究基金会;

关键词：

TRPV1; antagonists; Analgesic; Molecular modeling; Capsaicin; Resiniferatoxin; CAPSAICIN RECEPTORS; AGONISTS; CHANNEL; POTENT;

D O I：

10.1016/j.bmc.2011.11.008

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：

Structure-activity relationships for the A-region in a series of N-4-t-butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamides as TRPV1 antagonists have been investigated. Among them, the 3-fluoro analogue 54 showed high binding affinity and potent antagonism for both rTRPV1 and hTRPV1 in CHO cells. Its stereospecific activity was demonstrated with marked selectivity for the (S)-configuration (54S versus 54R). A docking study of 54S with our hTRPV1 homology model highlighted crucial hydrogen bonds between the ligand and the receptor contributing to its potency. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：215 / 224

页数：10

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