Discovery of indane propanamides as potent and selective TRPV1 antagonists

被引：12

作者：

Ahn, Songyeon ^{[1
]}

Kim, Yong Soo ^{[1
]}

Kim, Myeong Seup ^{[1
]}

Ann, Jihyae ^{[1
]}

Ha, Heejin ^{[2
]}

Yoo, Young Dong ^{[2
]}

Kim, Young Ho ^{[2
]}

Blumberg, Peter M. ^{[3
]}

Frank-Foltyn, Robert ^{[4
]}

Bahrenberg, Gregor ^{[4
]}

Stockhausen, Hannelore ^{[4
]}

Christoph, Thomas ^{[4
]}

Lee, Jeewoo ^{[1
]}

机构：

[1] Seoul Natl Univ, Coll Pharm, Lab Med Chem, Seoul 08826, South Korea

[2] Medifron DBT, Ansan 15426, Gyeonggi Do, South Korea

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

[4] Grunenthal GmbH, Grunenthal Innovat, D-52078 Aachen, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2020年 / 30卷 / 03期

基金：

新加坡国家研究基金会;

关键词：

Vanilloid receptor 1; TRPV1; antagonist; Analgesic; C-REGION ANALOGS; VANILLOID-1; ANTAGONISTS; CAPSAICIN RECEPTOR; 2-(3-FLUORO-4-METHYLSULFONYLAMINOPHENYL)PROPANAMIDES; PYRIDINE; PAIN; 2-(3-FLUORO-4-METHYLSULFONAMIDOPHENYL)PROPANAMIDES; PHARMACOLOGY;

D O I：

10.1016/j.bmcl.2019.126838

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of indane-type acetamide and propanamide analogues were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that indane A-region analogues exhibited better antagonism than did the corresponding 2,3-dihydrobenzofuran and 1,3-benzodioxole surrogates. Among them, antagonist 36 exhibited potent and selective antagonism toward capsaicin for hTRPV1 and mTRPV1. Further, in vivo studies indicated that antagonist 36 showed excellent analgesic activity in both phases of the formalin mouse pain model and inhibited the pain behavior completely at a dose of 1 mg/kg in the 2nd phase.

引用

页数：5

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