Asymmetric synthesis and receptor activity of chiral simplified resiniferatoxin (sRTX) analogues as transient receptor potential vanilloid 1 (TRPV1) ligands

被引：9

作者：

Kim, Myeong Seop ^{[1
]}

Ki, Yooran ^{[1
]}

Ahn, Song Yeon ^{[1
]}

Yoon, Suyoung ^{[1
]}

Kim, Sung-Eun ^{[1
]}

Park, Hyeung-Geun ^{[1
]}

Sun, Wei ^{[2
]}

Son, Karam ^{[3
,4
]}

Cui, Minghua ^{[3
,4
]}

Choi, Sun ^{[3
,4
]}

Pearce, Larry V. ^{[5
]}

Esch, Timothy E. ^{[5
]}

DeAndrea-Lazarus, Ian A. ^{[5
]}

Blumberg, Peter M. ^{[5
]}

Lee, Jeewoo ^{[1
]}

机构：

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

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

[3] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Natl Leading Res Lab Mol Modeling & Drug Design, Seoul 120750, South Korea

[4] Ewha Womans Univ, Global Top Res Program 5, Seoul 120750, South Korea

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

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24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：

Vanilloid receptor 1; TRPV1; antagonist; Capsaicin; Resiniferatoxin; Molecular modeling; CAPSAICIN RECEPTORS; ANTAGONISTS; DERIVATIVES;

D O I：

10.1016/j.bmcl.2013.10.064

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The chiral isomers of the two potent simplified RTX-based vanilloids, compounds 2 and 3, were synthesized employing highly enantioselective PTC alkylation and evaluated as hTRPV1 ligands. The analysis indicated that the R-isomer was the eutomer in binding affinity and functional activity. The agonism of compound 2R was comparable to that of RTX. Docking analysis of the chiral isomers of 3 suggested the basis for its stereospecific activity and the binding mode of 3R. (C) 2013 Elsevier Ltd. All rights reserved.

引用

页码：382 / 385

页数：4

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