• 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

相似文献

1
Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener.一系列N-芳基-双环[2.2.1]庚烷-2-甲酰胺的发现、合成及构效关系：新型KCNQ2和KCNQ4钾通道开放剂ML213的表征
ACS Chem Neurosci. 2011 Oct 19;2(10):572-577. doi: 10.1021/cn200065b.
2
A small molecule activator of KCNQ2 and KCNQ4 channels一种KCNQ2和KCNQ4通道的小分子激活剂
3
KCNQ2/3 openers show differential selectivity and site of action across multiple KCNQ channels.KCNQ2/3 开放剂对多种 KCNQ 通道表现出不同的选择性和作用部位。
J Neurosci Methods. 2011 Aug 30;200(1):54-62. doi: 10.1016/j.jneumeth.2011.06.014. Epub 2011 Jun 23.
4
Activation of expressed KCNQ potassium currents and native neuronal M-type potassium currents by the anti-convulsant drug retigabine.抗惊厥药物瑞替加滨对表达的KCNQ钾电流和天然神经元M型钾电流的激活作用。
J Neurosci. 2001 Aug 1;21(15):5535-45. doi: 10.1523/JNEUROSCI.21-15-05535.2001.
5
N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide (ICA-27243): a novel, selective KCNQ2/Q3 potassium channel activator.N-（6-氯吡啶-3-基）-3,4-二氟苯甲酰胺（ICA-27243）：一种新型的选择性KCNQ2/Q3钾通道激活剂。
Mol Pharmacol. 2008 Mar;73(3):977-86. doi: 10.1124/mol.107.043216. Epub 2007 Dec 18.
6
Structural insights into the lipid and ligand regulation of a human neuronal KCNQ channel.人类神经元KCNQ通道脂质和配体调控的结构见解
Neuron. 2022 Jan 19;110(2):237-247.e4. doi: 10.1016/j.neuron.2021.10.029. Epub 2021 Nov 11.
7
The KCNQ2/3 selective channel opener ICA-27243 binds to a novel voltage-sensor domain site.KCNQ2/3 选择性通道 opener ICA-27243 与一个新的电压传感器结构域位点结合。
Neurosci Lett. 2009 Nov 13;465(2):138-42. doi: 10.1016/j.neulet.2009.08.071. Epub 2009 Sep 3.
8
Discovery of Novel Retigabine Derivatives as Potent KCNQ4 and KCNQ5 Channel Agonists with Improved Specificity.新型瑞替加滨衍生物作为强效KCNQ4和KCNQ5通道激动剂且特异性增强的发现。
ACS Med Chem Lett. 2018 Dec 19;10(1):27-33. doi: 10.1021/acsmedchemlett.8b00315. eCollection 2019 Jan 10.
9
Single-channel analysis of KCNQ K+ channels reveals the mechanism of augmentation by a cysteine-modifying reagent.KCNQ钾离子通道的单通道分析揭示了一种半胱氨酸修饰试剂的增强机制。
J Neurosci. 2004 Jun 2;24(22):5079-90. doi: 10.1523/JNEUROSCI.0882-04.2004.
10
Identification of (R)-N-(4-(4-methoxyphenyl)thiazol-2-yl)-1-tosylpiperidine-2-carboxamide, ML277, as a novel, potent and selective K(v)7.1 (KCNQ1) potassium channel activator.鉴定（R）-N-（4-（4-甲氧基苯基）噻唑-2-基）-1-对甲苯磺酰基哌啶-2-甲酰胺，ML277，作为一种新型、有效和选择性的 K(v)7.1（KCNQ1）钾通道激活剂。
Bioorg Med Chem Lett. 2012 Sep 15;22(18):5936-41. doi: 10.1016/j.bmcl.2012.07.060. Epub 2012 Aug 2.

引用本文的文献

1
HO-mediated relaxation in a swine model of ischemic heart disease and exercise training: mechanistic insights and the role of Kv7 channels.HO介导的缺血性心脏病猪模型中的舒张功能及运动训练：机制见解与Kv7通道的作用
Basic Res Cardiol. 2025 Jul 12. doi: 10.1007/s00395-025-01129-6.
2
K7 Channel Activators Flupirtine and ML213 Alleviate Neuropathic Pain Behavior in the Streptozotocin Rat Model of Diabetic Neuropathy.K7通道激活剂氟吡汀和ML213减轻糖尿病性神经病变链脲佐菌素大鼠模型中的神经性疼痛行为。
J Pain Res. 2024 Jun 26;17:2267-2278. doi: 10.2147/JPR.S467535. eCollection 2024.
3
TET1 Participates in Complete Freund's Adjuvant-induced Trigeminal Inflammatory Pain by Regulating Kv7.2 in a Mouse Model.TET1 通过调节小鼠模型中的 Kv7.2 参与完全弗氏佐剂诱导的三叉神经炎性疼痛。
Neurosci Bull. 2024 Jun;40(6):707-718. doi: 10.1007/s12264-023-01139-1. Epub 2023 Nov 16.
4
A phenotypic screening platform for chronic pain therapeutics using all-optical electrophysiology.基于全光学电生理学的慢性疼痛治疗药物表型筛选平台。
Pain. 2024 Apr 1;165(4):922-940. doi: 10.1097/j.pain.0000000000003090. Epub 2023 Nov 14.
5
Overlooked KCNQ4 variants augment the risk of hearing loss.被忽视的 KCNQ4 变体增加了耳聋的风险。
Exp Mol Med. 2023 Apr;55(4):844-859. doi: 10.1038/s12276-023-00976-4. Epub 2023 Apr 3.
6
The Pathological Mechanisms of Hearing Loss Caused by and Variants.由[具体基因名称1]和[具体基因名称2]变异导致听力损失的病理机制。 （你提供的原文中“and”前后应该有具体的基因名称等信息，这里我按照格式补充了[具体基因名称1]和[具体基因名称2]）
Biomedicines. 2022 Sep 12;10(9):2254. doi: 10.3390/biomedicines10092254.
7
Triclosan is a KCNQ3 potassium channel activator.三氯生是一种 KCNQ3 钾通道激活剂。
Pflugers Arch. 2022 Jul;474(7):721-732. doi: 10.1007/s00424-022-02692-w. Epub 2022 Apr 22.
8
The Effectiveness in Activating M-Type K Current Produced by Solifenacin ([(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate): Independent of Its Antimuscarinic Action.索利那新（[(3R)-1-氮杂双环[2.2.2]辛烷-3-基]（1S）-1-苯基-3,4-二氢-1H-异喹啉-2-甲酰胺）激活 M 型钾电流的有效性：与其抗毒蕈碱作用无关。
Int J Mol Sci. 2021 Nov 17;22(22):12399. doi: 10.3390/ijms222212399.
9
Chemical modulation of Kv7 potassium channels.Kv7钾通道的化学调节
RSC Med Chem. 2021 Jan 14;12(4):483-537. doi: 10.1039/d0md00328j. eCollection 2021 Apr 28.
10
Activation of KCNQ4 as a Therapeutic Strategy to Treat Hearing Loss.激活KCNQ4作为治疗听力损失的一种治疗策略。
Int J Mol Sci. 2021 Mar 2;22(5):2510. doi: 10.3390/ijms22052510.

本文引用的文献

1
N-Pyridyl and Pyrimidine Benzamides as KCNQ2/Q3 Potassium Channel Openers for the Treatment of Epilepsy.作为用于治疗癫痫的KCNQ2/Q3钾通道开放剂的N-吡啶基和嘧啶苯甲酰胺
ACS Med Chem Lett. 2011 Mar 31;2(6):481-4. doi: 10.1021/ml200053x. eCollection 2011 Jun 9.
2
Design, synthesis and biological activity of pyrazolo[1,5-a]pyrimidin-7(4H)-ones as novel Kv7/KCNQ potassium channel activators.设计、合成及吡唑并[1,5-a]嘧啶-7(4H)-酮类化合物作为新型 Kv7/KCNQ 钾通道激活剂的生物活性。
Eur J Med Chem. 2011 Mar;46(3):934-43. doi: 10.1016/j.ejmech.2011.01.010. Epub 2011 Jan 22.
3
Isoform-specific prolongation of Kv7 (KCNQ) potassium channel opening mediated by new molecular determinants for drug-channel interactions.新型药物-通道相互作用分子决定因素介导的 Kv7（KCNQ）钾通道开放的亚型特异性延长。
J Biol Chem. 2010 Sep 3;285(36):28322-32. doi: 10.1074/jbc.M110.116392. Epub 2010 Jun 28.
4
Novel KCNQ2/Q3 agonists as potential therapeutics for epilepsy and neuropathic pain.新型 KCNQ2/Q3 激动剂有望成为治疗癫痫和神经病理性疼痛的药物。
J Med Chem. 2010 Jan 28;53(2):887-96. doi: 10.1021/jm901497b.
5
In vivo profile of ICA-27243 [N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide], a potent and selective KCNQ2/Q3 (Kv7.2/Kv7.3) activator in rodent anticonvulsant models.ICA-27243 [N-(6-氯吡啶-3-基)-3,4-二氟苯甲酰胺]在啮齿动物抗惊厥模型中的体内概况，一种强效且选择性的KCNQ2/Q3（Kv7.2/Kv7.3）激活剂
J Pharmacol Exp Ther. 2008 Sep;326(3):818-28. doi: 10.1124/jpet.108.137794. Epub 2008 Jun 24.
6
The therapeutic potential of neuronal K V 7 (KCNQ) channel modulators: an update.神经元K V 7（KCNQ）通道调节剂的治疗潜力：最新进展
Expert Opin Ther Targets. 2008 May;12(5):565-81. doi: 10.1517/14728222.12.5.565.
7
Activation of Kv7 (KCNQ) voltage-gated potassium channels by synthetic compounds.合成化合物对Kv7（KCNQ）电压门控钾通道的激活作用。
Trends Pharmacol Sci. 2008 Feb;29(2):99-107. doi: 10.1016/j.tips.2007.11.010. Epub 2008 Jan 18.
8
Kv7 (KCNQ) channel modulators and neuropathic pain.Kv7（KCNQ）通道调节剂与神经性疼痛。
J Med Chem. 2007 May 31;50(11):2576-82. doi: 10.1021/jm060989l. Epub 2007 May 10.
9
Randomized, multicenter, dose-ranging trial of retigabine for partial-onset seizures.瑞替加滨用于部分性发作癫痫的随机、多中心、剂量范围试验。
Neurology. 2007 Apr 10;68(15):1197-204. doi: 10.1212/01.wnl.0000259034.45049.00.
10
Synthesis and KCNQ2 opener activity of N-(1-benzo[1,3]dioxol-5-yl-ethyl, N-[1-(2,3-dihydro-benzofuran-5-yl)-ethyl, and N-[1-(2,3-dihydro-1H-indol-5-yl)-ethyl acrylamides.N-(1-苯并[1,3]二氧杂环戊烯-5-基-乙基)、N-[1-(2,3-二氢苯并呋喃-5-基)-乙基]和N-[1-(2,3-二氢-1H-吲哚-5-基)-乙基]丙烯酰胺的合成及KCNQ2开放剂活性
Bioorg Med Chem Lett. 2004 Sep 6;14(17):4533-7. doi: 10.1016/j.bmcl.2004.06.035.

一系列N-芳基-双环[2.2.1]庚烷-2-甲酰胺的发现、合成及构效关系：新型KCNQ2和KCNQ4钾通道开放剂ML213的表征

Discovery, Synthesis, and Structure Activity Relationship of a Series of N-Aryl- bicyclo[2.2.1]heptane-2-carboxamides: Characterization of ML213 as a Novel KCNQ2 and KCNQ4 Potassium Channel Opener.

作者信息

Yu Haibo, Wu Meng, Townsend Steven D, Zou Beiyan, Long Shunyou, Daniels J Scott, McManus Owen B, Li Min, Lindsley Craig W, Hopkins Corey R

机构信息

Department of Neuroscience, High Throughput Biology Center, Johns Hopkins University, Baltimore, Maryland 21205, United States.

出版信息

ACS Chem Neurosci. 2011 Oct 19;2(10):572-577. doi: 10.1021/cn200065b.

DOI:10.1021/cn200065b
PMID:22125664
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3223964/
Abstract

Herein we report the discovery, synthesis and evaluation of a series of N-Aryl-bicyclo[2.2.1]heptane-2-carboxamides as selective KCNQ2 (K(v)7.2) and KCNQ4 (K(v)7.4) channel openers. The best compound, 1 (ML213) has an EC(50) of 230 nM (KCNQ2) and 510 nM (KCNQ4) and is selective for KCNQ2 and KCNQ4 channels versus a large battery of related potassium channels, as well as affording modest brain levels. This represents the first report of unique selectivity profile for KCNQ2 and KCNQ4 over the other channels (KCNQ1/3/5) and as such should prove to be a valuable tool compound for understanding these channels in regulating neuronal activity.

摘要

在此，我们报告了一系列N-芳基双环[2.2.1]庚烷-2-甲酰胺作为选择性KCNQ2（K(v)7.2）和KCNQ4（K(v)7.4）通道开放剂的发现、合成及评价。最佳化合物1（ML213）对KCNQ2的半数有效浓度（EC(50)）为230 nM，对KCNQ4为510 nM，相对于大量相关钾通道，它对KCNQ2和KCNQ4通道具有选择性，并且在脑中能达到适度的浓度水平。这是关于KCNQ2和KCNQ4相对于其他通道（KCNQ1/3/5）具有独特选择性谱的首次报道，因此应证明是理解这些通道在调节神经元活动方面的一种有价值的工具化合物。