• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

具有高镇痛疗效的 TRPV1 拮抗剂：2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的 2-噻吩基 C-区类似物。

TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides.

机构信息

Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.

出版信息

Bioorg Med Chem. 2013 Nov 1;21(21):6657-64. doi: 10.1016/j.bmc.2013.08.015. Epub 2013 Aug 13.

DOI:10.1016/j.bmc.2013.08.015
PMID:24035514
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6957258/
Abstract

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.

摘要

研究了一系列 2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的 2-硫代吡啶 C-区域类似物，作为 hTRPV1 拮抗剂。其中，化合物 24S 对辣椒素诱导的激活表现出立体特异性和优异的 TRPV1 拮抗作用。此外，它在大鼠神经病理性疼痛模型中表现出强烈的抗痛觉过敏作用。与体外作用一致，化合物 24S 阻断了小鼠辣椒素诱导的体温过低。用我们的 hTRPV1 同源模型进行了 24S 的对接分析，以确定其结合模式。

相似文献

1
TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides.具有高镇痛疗效的 TRPV1 拮抗剂：2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的 2-噻吩基 C-区类似物。
Bioorg Med Chem. 2013 Nov 1;21(21):6657-64. doi: 10.1016/j.bmc.2013.08.015. Epub 2013 Aug 13.
2
Pyridine C-region analogs of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的吡啶C-区域类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Eur J Med Chem. 2015 Mar 26;93:101-8. doi: 10.1016/j.ejmech.2015.02.001. Epub 2015 Feb 2.
3
2-Alkyl/alkenyl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的2-烷基/烯基取代吡啶C区类似物作为高效TRPV1拮抗剂。
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4039-43. doi: 10.1016/j.bmcl.2014.05.074. Epub 2014 Jun 2.
4
2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的2-芳基取代吡啶C区域类似物作为高效TRPV1拮抗剂。
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4044-7. doi: 10.1016/j.bmcl.2014.05.072. Epub 2014 Jun 2.
5
2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: structure activity relationships of the 2-oxy pyridine C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺类作为强效 TRPV1 拮抗剂：2-氧代吡啶 C 区的结构活性关系。
Eur J Med Chem. 2013 Jun;64:589-602. doi: 10.1016/j.ejmech.2013.04.003. Epub 2013 Apr 11.
6
t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的叔丁基吡啶和苯基C区域类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem. 2017 Apr 15;25(8):2451-2462. doi: 10.1016/j.bmc.2017.03.004. Epub 2017 Mar 6.
7
2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺作为有效的瞬时受体电位香草酸 1（TRPV1）拮抗剂：N-(6-三氟甲基吡啶-3-基甲基)C 区 2-氨基衍生物的结构活性关系。
J Med Chem. 2012 Oct 11;55(19):8392-408. doi: 10.1021/jm300780p. Epub 2012 Sep 20.
8
Structure activity relationships of benzyl C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰胺基苯基)丙酰胺的苄基C区域类似物作为有效的TRPV1拮抗剂的构效关系
Bioorg Med Chem. 2015 Nov 1;23(21):6844-54. doi: 10.1016/j.bmc.2015.10.001. Epub 2015 Oct 9.
9
Discovery of indane propanamides as potent and selective TRPV1 antagonists.茚满丙酰胺作为强效和选择性TRPV1拮抗剂的发现。
Bioorg Med Chem Lett. 2020 Feb 1;30(3):126838. doi: 10.1016/j.bmcl.2019.126838. Epub 2019 Dec 3.
10
4-Aminophenyl acetamides and propanamides as potent transient receptor potential vanilloid 1 (TRPV1) ligands.4-氨基苯乙酰胺和丙酰胺类化合物作为潜在的瞬时受体电位香草酸 1 型（TRPV1）配体。
Bioorg Med Chem. 2018 Aug 15;26(15):4509-4517. doi: 10.1016/j.bmc.2018.07.040. Epub 2018 Jul 25.

引用本文的文献

1
A new era for the design of TRPV1 antagonists and agonists with the use of structural information and molecular docking of capsaicin-like compounds.利用结构信息和辣椒素类似物的分子对接设计 TRPV1 拮抗剂和激动剂的新时代。
J Enzyme Inhib Med Chem. 2022 Dec;37(1):2169-2178. doi: 10.1080/14756366.2022.2110089.
2
Computational Modeling to Explain Why 5,5-Diarylpentadienamides are TRPV1 Antagonists.用于解释5,5-二芳基戊二烯酰胺为何是瞬时受体电位香草酸亚型1（TRPV1）拮抗剂的计算模型
Molecules. 2021 Mar 21;26(6):1765. doi: 10.3390/molecules26061765.
3
Pyrazole C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.

本文引用的文献

1
2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: structure activity relationships of the 2-oxy pyridine C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺类作为强效 TRPV1 拮抗剂：2-氧代吡啶 C 区的结构活性关系。
Eur J Med Chem. 2013 Jun;64:589-602. doi: 10.1016/j.ejmech.2013.04.003. Epub 2013 Apr 11.
2
Screening TRPV1 antagonists for the treatment of pain: lessons learned over a decade.TRPV1 拮抗剂治疗疼痛的筛选：十余年的经验教训。
Expert Opin Drug Discov. 2009 Feb;4(2):159-80. doi: 10.1517/17460440802681300.
3
Multisteric TRPV1 nocisensor: a target for analgesics.
2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的吡唑C区类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem Lett. 2017 Sep 15;27(18):4383-4388. doi: 10.1016/j.bmcl.2017.08.020. Epub 2017 Aug 12.
4
t-Butyl pyridine and phenyl C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的叔丁基吡啶和苯基C区域类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem. 2017 Apr 15;25(8):2451-2462. doi: 10.1016/j.bmc.2017.03.004. Epub 2017 Mar 6.
5
Discovery of N-(3-fluoro-4-methylsulfonamidomethylphenyl)urea as a potent TRPV1 antagonistic template.发现N-（3-氟-4-甲基磺酰胺基甲基苯基）脲作为一种有效的TRPV1拮抗剂模板。
Bioorg Med Chem Lett. 2016 Aug 1;26(15):3603-7. doi: 10.1016/j.bmcl.2016.06.010. Epub 2016 Jun 7.
6
2-Sulfonamidopyridine C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰胺基苯基)丙酰胺的2-磺酰胺基吡啶C区类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Bioorg Med Chem. 2016 Mar 15;24(6):1231-40. doi: 10.1016/j.bmc.2016.01.051. Epub 2016 Jan 28.
7
Structure activity relationships of benzyl C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰胺基苯基)丙酰胺的苄基C区域类似物作为有效的TRPV1拮抗剂的构效关系
Bioorg Med Chem. 2015 Nov 1;23(21):6844-54. doi: 10.1016/j.bmc.2015.10.001. Epub 2015 Oct 9.
8
α-Substituted 2-(3-fluoro-4-methylsulfonamidophenyl)acetamides as potent TRPV1 antagonists.α-取代的2-(3-氟-4-甲基磺酰胺基苯基)乙酰胺作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂。
Bioorg Med Chem Lett. 2015 Jun 1;25(11):2326-30. doi: 10.1016/j.bmcl.2015.04.024. Epub 2015 Apr 12.
9
Pyridine C-region analogs of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists.2-(3-氟-4-甲基磺酰氨基苯基)丙酰胺的吡啶C-区域类似物作为有效的瞬时受体电位香草酸亚型1（TRPV1）拮抗剂
Eur J Med Chem. 2015 Mar 26;93:101-8. doi: 10.1016/j.ejmech.2015.02.001. Epub 2015 Feb 2.
10
2-Aryl substituted pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as highly potent TRPV1 antagonists.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺的2-芳基取代吡啶C区域类似物作为高效TRPV1拮抗剂。
Bioorg Med Chem Lett. 2014 Aug 15;24(16):4044-7. doi: 10.1016/j.bmcl.2014.05.072. Epub 2014 Jun 2.
多聚体 TRPV1 伤害感受器：镇痛药的作用靶点。
Trends Pharmacol Sci. 2012 Dec;33(12):646-55. doi: 10.1016/j.tips.2012.09.002. Epub 2012 Oct 12.
4
2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as potent transient receptor potential vanilloid 1 (TRPV1) antagonists: structure-activity relationships of 2-amino derivatives in the N-(6-trifluoromethylpyridin-3-ylmethyl) C-region.2-(3-氟-4-甲磺酰氨基苯基)丙酰胺作为有效的瞬时受体电位香草酸 1（TRPV1）拮抗剂：N-(6-三氟甲基吡啶-3-基甲基)C 区 2-氨基衍生物的结构活性关系。
J Med Chem. 2012 Oct 11;55(19):8392-408. doi: 10.1021/jm300780p. Epub 2012 Sep 20.
5
Targeting TRPV1 for pain relief: limits, losers and laurels.针对 TRPV1 缓解疼痛：限制、输家和胜利者。
Expert Opin Investig Drugs. 2012 Sep;21(9):1351-69. doi: 10.1517/13543784.2012.704021. Epub 2012 Jul 11.
6
N-4-t-Butylbenzyl 2-(4-methylsulfonylaminophenyl) propanamide TRPV1 antagonists: Structure-activity relationships in the A-region.N-4-叔丁基苄基 2-(4-甲磺酰胺基苯基)丙酰胺 TRPV1 拮抗剂：A 区域的结构-活性关系。
Bioorg Med Chem. 2012 Jan 1;20(1):215-24. doi: 10.1016/j.bmc.2011.11.008. Epub 2011 Nov 22.
7
Structural insights into transient receptor potential vanilloid type 1 (TRPV1) from homology modeling, flexible docking, and mutational studies.同源建模、柔性对接和突变研究揭示瞬时受体电位香草酸亚型 1（TRPV1）的结构见解。
J Comput Aided Mol Des. 2011 Apr;25(4):317-27. doi: 10.1007/s10822-011-9421-5. Epub 2011 Mar 30.
8
Transient receptor potential vanilloid-1 antagonists: a survey of recent patent literature.瞬时受体电位香草酸 1 型拮抗剂：近期专利文献综述。
Expert Opin Ther Pat. 2010 Sep;20(9):1107-22. doi: 10.1517/13543776.2010.497756.
9
Analgesic potential of TRPV1 antagonists.瞬时受体电位香草酸亚型1（TRPV1）拮抗剂的镇痛潜力。
Biochem Pharmacol. 2009 Aug 1;78(3):211-6. doi: 10.1016/j.bcp.2009.02.014. Epub 2009 Mar 5.
10
Therapeutic potential of vanilloid receptor TRPV1 agonists and antagonists as analgesics: Recent advances and setbacks.香草酸受体TRPV1激动剂和拮抗剂作为镇痛药的治疗潜力：最新进展与挫折
Brain Res Rev. 2009 Apr;60(1):267-77. doi: 10.1016/j.brainresrev.2008.12.006. Epub 2008 Dec 25.