• 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

新型3-氟-6-甲氧基喹啉衍生物作为细菌DNA促旋酶和拓扑异构酶IV的抑制剂

Novel 3-fluoro-6-methoxyquinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV.

作者信息

Mitton-Fry Mark J, Brickner Steven J, Hamel Judith C, Barham Rose, Brennan Lori, Casavant Jeffrey M, Ding Xiaoyuan, Finegan Steven, Hardink Joel, Hoang Thuy, Huband Michael D, Maloney Meghan, Marfat Anthony, McCurdy Sandra P, McLeod Dale, Subramanyam Chakrapani, Plotkin Michael, Reilly Usa, Schafer John, Stone Gregory G, Uccello Daniel P, Wisialowski Todd, Yoon Kwansik, Zaniewski Richard, Zook Christopher

机构信息

Pfizer Worldwide Research and Development, Groton, CT 06340, USA.

Pfizer Worldwide Research and Development, Groton, CT 06340, USA.

出版信息

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3353-3358. doi: 10.1016/j.bmcl.2017.06.009. Epub 2017 Jun 3.

DOI:10.1016/j.bmcl.2017.06.009
PMID:28610977
Abstract

Novel (non-fluoroquinolone) inhibitors of bacterial type II topoisomerases (NBTIs) are an emerging class of antibacterial agents. We report an optimized series of cyclobutylaryl-substituted NBTIs. Compound 14 demonstrated excellent activity both in vitro (S. aureus MIC=0.125μg/mL) and in vivo (systemic and tissue infections). Enhanced inhibition of Topoisomerase IV correlated with improved activity in S. aureus strains with mutations conferring resistance to NBTIs. Compound 14 also displayed an improved hERG IC of 85.9μM and a favorable profile in the anesthetized guinea pig model.

摘要

新型（非氟喹诺酮类）细菌II型拓扑异构酶抑制剂（NBTIs）是一类新兴的抗菌剂。我们报道了一系列经过优化的环丁基芳基取代的NBTIs。化合物14在体外（金黄色葡萄球菌MIC = 0.125μg/mL）和体内（全身和组织感染）均表现出优异的活性。对拓扑异构酶IV的抑制增强与对NBTIs耐药的金黄色葡萄球菌菌株活性提高相关。化合物14还表现出改善的hERG IC为85.9μM，并且在麻醉豚鼠模型中具有良好的特性。

相似文献

1
Novel 3-fluoro-6-methoxyquinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV.新型3-氟-6-甲氧基喹啉衍生物作为细菌DNA促旋酶和拓扑异构酶IV的抑制剂
Bioorg Med Chem Lett. 2017 Aug 1;27(15):3353-3358. doi: 10.1016/j.bmcl.2017.06.009. Epub 2017 Jun 3.
2
Novel quinoline derivatives as inhibitors of bacterial DNA gyrase and topoisomerase IV.新型喹啉衍生物作为细菌 DNA 回旋酶和拓扑异构酶 IV 的抑制剂。
Bioorg Med Chem Lett. 2013 May 15;23(10):2955-61. doi: 10.1016/j.bmcl.2013.03.047. Epub 2013 Mar 21.
3
Discovery of aminopiperidine based potent & novel topoisomerase inhibitor with broad spectrum anti-bacterial activity.发现具有广谱抗菌活性的基于氨基哌啶的新型拓扑异构酶抑制剂。
Bioorg Med Chem Lett. 2024 Oct 1;111:129911. doi: 10.1016/j.bmcl.2024.129911. Epub 2024 Jul 26.
4
Molecular docking, discovery, synthesis, and pharmacological properties of new 6-substituted-2-(3-phenoxyphenyl)-4-phenyl quinoline derivatives; an approach to developing potent DNA gyrase inhibitors/antibacterial agents.新型6-取代-2-(3-苯氧基苯基)-4-苯基喹啉衍生物的分子对接、发现、合成及药理性质；一种开发强效DNA回旋酶抑制剂/抗菌剂的方法
Bioorg Med Chem. 2017 Feb 15;25(4):1448-1455. doi: 10.1016/j.bmc.2017.01.007. Epub 2017 Jan 6.
5
Synthesis and anti-staphylococcal activity of novel bacterial topoisomerase inhibitors with a 5-amino-1,3-dioxane linker moiety.具有5-氨基-1,3-二氧杂环己烷连接基团的新型细菌拓扑异构酶抑制剂的合成及其抗葡萄球菌活性
Bioorg Med Chem Lett. 2018 Aug 1;28(14):2477-2480. doi: 10.1016/j.bmcl.2018.06.003. Epub 2018 Jun 1.
6
Design, synthesis, and antibacterial evaluation of new quinoline-1,3,4-oxadiazole and quinoline-1,2,4-triazole hybrids as potential inhibitors of DNA gyrase and topoisomerase IV.新型喹啉-1,3,4-噁二唑和喹啉-1,2,4-三唑杂合体的设计、合成及抗菌活性评价，作为 DNA 回旋酶和拓扑异构酶 IV 的潜在抑制剂。
Bioorg Chem. 2021 Jul;112:104920. doi: 10.1016/j.bioorg.2021.104920. Epub 2021 Apr 19.
7
Design, green one-pot synthesis and molecular docking study of novel N,N-bis(cyanoacetyl)hydrazines and bis-coumarins as effective inhibitors of DNA gyrase and topoisomerase IV.新型 N,N-双（氰乙酰基）腙和双香豆素的设计、绿色一锅合成及分子对接研究，作为 DNA 拓扑异构酶 II 和拓扑异构酶 IV 的有效抑制剂。
Bioorg Chem. 2020 Apr;97:103672. doi: 10.1016/j.bioorg.2020.103672. Epub 2020 Feb 16.
8
Selenophene-containing inhibitors of type IIA bacterial topoisomerases.含硒吩的 IIA 型细菌拓扑异构酶抑制剂。
J Med Chem. 2011 May 12;54(9):3418-25. doi: 10.1021/jm2002124. Epub 2011 Apr 13.
9
Structure activity relationship of C-2 ether substituted 1,5-naphthyridine analogs of oxabicyclooctane-linked novel bacterial topoisomerase inhibitors as broad-spectrum antibacterial agents (Part-5).作为广谱抗菌剂的氧杂双环辛烷连接的新型细菌拓扑异构酶抑制剂的C-2醚取代1,5-萘啶类似物的构效关系（第5部分）
Bioorg Med Chem Lett. 2015 Sep 1;25(17):3630-5. doi: 10.1016/j.bmcl.2015.06.061. Epub 2015 Jun 23.
10
Design, synthesis and biological evaluation of α-substituted isonipecotic acid benzothiazole analogues as potent bacterial type II topoisomerase inhibitors.设计、合成及生物评价 α-取代异哌啶酸苯并噻唑类似物作为强效的细菌拓扑异构酶 II 抑制剂。
Bioorg Med Chem Lett. 2013 Dec 15;23(24):6598-603. doi: 10.1016/j.bmcl.2013.10.058. Epub 2013 Nov 4.

引用本文的文献

1
Synthesis of ciprofloxacin-linked 1,2,3-triazole conjugates as potent antibacterial agents using click chemistry: exploring their function as DNA gyrase inhibitors - and -based studies.利用点击化学合成环丙沙星连接的1,2,3-三唑共轭物作为强效抗菌剂：探索其作为DNA促旋酶抑制剂的功能及相关研究
RSC Adv. 2024 May 30;14(24):17051-17070. doi: 10.1039/d4ra01332h. eCollection 2024 May 22.
2
Dynamic Profiling and Binding Affinity Prediction of NBTI Antibacterials against DNA Gyrase Enzyme by Multidimensional Machine Learning and Molecular Dynamics Simulations.通过多维机器学习和分子动力学模拟对NBTI抗菌剂针对DNA旋转酶的动态分析和结合亲和力预测
ACS Omega. 2024 Apr 11;9(16):18278-18295. doi: 10.1021/acsomega.4c00036. eCollection 2024 Apr 23.
3
Interactions between Gepotidacin and Gyrase and Topoisomerase IV: Genetic and Biochemical Evidence for Well-Balanced Dual-Targeting.Gepotidacin 与拓扑异构酶 IV 和拓扑异构酶 V 的相互作用：双重靶向平衡的遗传和生化证据。
ACS Infect Dis. 2024 Apr 12;10(4):1137-1151. doi: 10.1021/acsinfecdis.3c00346. Epub 2024 Mar 5.
4
Gyrase and Topoisomerase IV: Recycling Old Targets for New Antibacterials to Combat Fluoroquinolone Resistance.回旋酶和拓扑异构酶 IV：回收旧靶点用于新型抗菌药物以对抗氟喹诺酮耐药性。
ACS Infect Dis. 2024 Apr 12;10(4):1097-1115. doi: 10.1021/acsinfecdis.4c00128. Epub 2024 Apr 2.
5
Antibacterial and Antifungal Alkaloids from Asian Angiosperms: Distribution, Mechanisms of Action, Structure-Activity, and Clinical Potentials.亚洲被子植物中的抗菌和抗真菌生物碱：分布、作用机制、构效关系及临床潜力
Antibiotics (Basel). 2022 Aug 24;11(9):1146. doi: 10.3390/antibiotics11091146.
6
The Structural Features of Novel Bacterial Topoisomerase Inhibitors That Define Their Activity on Topoisomerase IV.新型细菌拓扑异构酶抑制剂的结构特征决定了它们对拓扑异构酶 IV 的活性。
J Med Chem. 2022 May 12;65(9):6431-6440. doi: 10.1021/acs.jmedchem.2c00039. Epub 2022 May 3.
7
Structure-Activity Relationship of Anti- Piperidine-4-carboxamides, a New Class of NBTI DNA Gyrase Inhibitors.新型NBTI DNA回旋酶抑制剂——抗哌啶-4-羧酰胺的构效关系
ACS Med Chem Lett. 2022 Feb 28;13(3):417-427. doi: 10.1021/acsmedchemlett.1c00549. eCollection 2022 Mar 10.
8
Dioxane-Linked Amide Derivatives as Novel Bacterial Topoisomerase Inhibitors against Gram-Positive .二恶烷连接的酰胺衍生物作为新型抗革兰氏阳性菌的细菌拓扑异构酶抑制剂
ACS Med Chem Lett. 2020 Oct 19;11(12):2446-2454. doi: 10.1021/acsmedchemlett.0c00428. eCollection 2020 Dec 10.
9
Two Decades of Successful SAR-Grounded Stories of the Novel Bacterial Topoisomerase Inhibitors (NBTIs).两 decade 成功的 SAR 为基础的 novel 细菌拓扑异构酶抑制剂（NBTIs）的故事。
J Med Chem. 2020 Jun 11;63(11):5664-5674. doi: 10.1021/acs.jmedchem.9b01738. Epub 2020 Feb 17.
10
Bimodal Actions of a Naphthyridone/Aminopiperidine-Based Antibacterial That Targets Gyrase and Topoisomerase IV.基于萘啶酮/氨基哌啶的抗菌药物的双重作用模式，该药物靶向拓扑异构酶 II 和拓扑异构酶 IV。
Biochemistry. 2019 Nov 5;58(44):4447-4455. doi: 10.1021/acs.biochem.9b00805. Epub 2019 Oct 28.