diethyl [(2-fluoroanilino)methylidene]malonate | 63010-68-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: diethyl [(2-fluoroanilino)methylidene]malonate
• 英文别名: diethyl 2-(2-fluoroanilino)methylenemalonate；2-fluoroanilinmethylenemalonate diethyl ester；diethyl 2-(((2-fluorophenyl)amino)methylene)malonate；o-fluoroanilinmethylenemalonate diethyl ester；2-[(2-fluoro-phenylamino)-methylene]-malonic acid diethyl ester；1,3-Diethyl 2-{[(2-fluorophenyl)amino]methylidene}propanedioate；diethyl 2-[(2-fluoroanilino)methylidene]propanedioate
• CAS: 63010-68-4
• 化学式: C₁₄H₁₆FNO₄
• mdl: MFCD00017907
• 分子量: 281.284
• InChiKey: MSFAOJKKCLDGQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.285
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2922499990

反应信息

• 作为反应物：
  描述：

  diethyl [(2-fluoroanilino)methylidene]malonate 以 diphenyl ether-biphenyl eutectic 为溶剂， 生成 1,4-二羟基-8-氟-4-羰基喹啉-3-羧酸乙酯
  参考文献：
  名称：

  喹啉-3-甲酰胺，含砜作为肝X受体（LXR）激动剂，对LXRβ具有结合选择性，且血脑渗透率低

  摘要：

  制备了一系列包含喹啉-3-甲酰胺的砜，发现它们具有对LXRβ的良好结合亲和力和对LXRα的中等结合选择性。TPSA得分高的8-Cl喹啉类似物33对LXRβ的结合选择性超过LXRα的34倍（LXRβIC 50  = 16 nM），在THP巨噬细胞系中诱导ABCA1基因表达的活性良好，所需的弱效LXRαGal4功能测定和低血脑屏障穿透力在大鼠中。

  DOI：

  10.1016/j.bmcl.2009.11.062
• 作为产物：
  描述：

  丙二酸二乙酯 在 乙酸酐 、 zinc(II) chloride 作用下， 以 乙醇 为溶剂， 反应 6.0h， 生成 diethyl [(2-fluoroanilino)methylidene]malonate
  参考文献：
  名称：

  Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

  摘要：

  A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV-vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b-DNA complex which might block DNA replication and thus exert its antimicrobial activities. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.03.118

文献信息

• Synthesis and screening of triazolopyrimidine scaffold as multi-functional agents for Alzheimer's disease therapies
  作者：Jitendra Kumar、Poonam Meena、Anju Singh、Ehtesham Jameel、Mudasir Maqbool、Mohammad Mobashir、Ashutosh Shandilya、Manisha Tiwari、Nasimul Hoda、B. Jayaram

  DOI：10.1016/j.ejmech.2016.04.053

  日期：2016.8

  acetylcholinesterase inhibitors (AChEIs). Molecular docking and scoring was utilized for the design of inhibitors. The molecules were synthesized via an easily accessible, convergent synthetic route. Three triazolopyrimidine based compounds showed nanomolar activity towards acetylcholinesterase. Among them, Ethyl 6-fluoro-4-(4-(5-methyl-[1,2,4]triazolo[1,5-a]pyrimidin-7-yl)piperazin-1-yl)quinoline-3-carboxylate (10d)

  在本研究中，设计，合成和评估了一系列三唑并嘧啶-喹啉和氰基吡啶-喹啉杂化物，作为乙酰胆碱酯酶抑制剂（AChEI）。分子对接和评分用于抑制剂的设计。分子是通过容易获得的，会聚的合成途径合成的。三种基于三唑并嘧啶的化合物显示出对乙酰胆碱酯酶的纳摩尔活性。其中，乙基6-氟-4-（4-（5-甲基-[1,2,4]三唑并[1,5-a]嘧啶-7-基）哌嗪-1-基）喹啉-3-羧酸酯（10d），强烈抑制AChE，IC 50值为42 nM。此外化合物10d被认为是对丁酰胆碱酯酶（BuChE）具有12倍选择性的最有前途的化合物。该化合物显示出组成的多目标概况，并有望抑制自身诱导的和AChE诱导的Aβ聚集以及抗氧化活性。
• 3-(Benzo[<i>d</i>]thiazol-2-yl)-4-aminoquinoline derivatives as novel scaffold topoisomerase I inhibitor <i>via</i> DNA intercalation: design, synthesis, and antitumor activities
  作者：Jing-Mei Yuan、Nan-Ying Chen、Hao-Ran Liao、Guo-Hai Zhang、Xiao-Juan Li、Zi-Yu Gu、Cheng-Xue Pan、Dong-Liang Mo、Gui-Fa Su

  DOI：10.1039/c9nj05846j

  日期：——

  Twenty-seven 3-(benzo[d]thiazol-2-yl)-4-aminoquinoline derivatives have been designed and synthesized as topoisomerase I inhibitors. The in vitro anti-proliferation evaluation against four human cancer cell lines (MGC-803, HepG-2, T24, and NCI-H460) and one normal cell line (HL-7702) indicated that most of them exhibited potent cytotoxicity. Among them, 5a was identified as the most promising candidate

  已经设计并合成了二十七个3-（苯并[ d ]噻唑-2-基）-4-氨基喹啉衍生物作为拓扑异构酶I抑制剂。在体外针对四种人类肿瘤细胞系（MGC-803，人肝癌HepG-2，T24，和NCI-H460）和一个正常细胞系的抗增殖评价（HL-7702）表示，其中大部分表现出强的细胞毒性。其中，5a被认为是最有前途的候选物，其IC 50值低至约2.20±0.14，并被选作进一步探索。光谱分析和琼脂糖凝胶电泳分析表明5a可以与DNA相互作用并强烈抑制拓扑异构酶I（Topo I）。进一步筛选化合物5b的Topo I活性，5c，5e，5f，5h，5i，5j，5l和5n表明一些化合物可能与5a具有完全不同的细胞毒性。分子建模研究证实5a采用独特的模式与DNA和Topo I相互作用。其他分子机理研究表明，用5a处理MGC-803细胞可诱导S期阻滞，上调促凋亡蛋白，下调抗凋亡蛋白，激活caspase-3，随后诱导
• A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy
  作者：Luca Agnetta、Michael Kauk、Maria Consuelo Alonso Canizal、Regina Messerer、Ulrike Holzgrabe、Carsten Hoffmann、Michael Decker

  DOI：10.1002/anie.201701524

  日期：2017.6.12

  synthetically incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized the photophysical properties of this ligand called BQCAAI and investigated its applicability as a pharmacological tool compound with a set of FRET techniques at the M1 receptor. BQCAAI proved to be an unprecedented molecular tool; it is the first photoswitchable dualsteric ligand, and its activity can be regulated

  尽管总体上M受体和GPCR具有巨大的治疗意义，但对G蛋白偶联受体（GPCR）尤其是毒蕈碱型乙酰胆碱（mACh或M）受体激活的方式和时程的研究仍处于起步阶段。 。我们在本文中使用了双立体配体，该配体可以与直立的同时与神经递质，结合位点和变构的配体相互作用。我们合成了一个可光开关的（光致变色）偶氮苯部分。我们表征了这种称为BQCAAI的配体的光物理性质，并通过一套FRET技术在M 1处研究了其作为药理学工具化合物的适用性。受体。BQCAAI被证明是前所未有的分子工具。它是第一个可光转换的双空间配体，其活性可以受光调节。我们还应用了BQCCAI来研究几种受体激活过程的时间过程。
• Synthesis of 6-aryl substituted 4-quinolones via Suzuki cross coupling
  作者：Sumanta Gupta、Prasanjit Ghosh、Seema Dwivedi、Sajal Das

  DOI：10.1039/c3ra45056b

  日期：——

  A convenient way to introduce aryl functionalization in the 6-position of 4-quinolones is developed via selective bromination and subsequent arylation by Suzuki cross-coupling. Ethyl 4-quinolone 3-carboxylates were subjected to selective bromination at C-6 followed by arylation under microwave irradiation that yielded the desired cross-coupling products within 5 minutes. This approach can expediently

  通过选择性溴化和随后通过铃木交叉偶联的芳基化作用，开发了一种在4-喹诺酮的6-位引入芳基官能化的简便方法。使4-喹诺酮3-羧酸乙酯在C-6处选择性溴化，然后在微波辐射下进行芳基化，在5分钟内产生所需的交叉偶联产物。该方法可方便地用于芳基官能化的4-喹诺酮衍生物（一类重要的生物活性化合物）的文库合成。
• Microwave-Assisted Synthesis of Fluoroquinolones and Their Nucleosides as Inhibitors of HIV Integrase
  作者：Martina M. Adams、Jan W. Bats、Nadja V. Nikolaus、Myriam Witvrouw、Zeger Debyser、Joachim W. Engels

  DOI：10.1135/cccc20060978

  日期：——

  Six fluoroquinolone ribonucleosides were synthesized by using microwave irradiation starting from fluoroanilines. In most cases the microwave application proved superior in time and yield, especially the one step decarboxylation of the carboxyquinolone esters3a-3cand the Vorbrüggen glycosylation. The former led to the new type of fluoroquinolone ribosides8a-8c. Compound8cin the crystal structure showed C3'-endo and anti conformation. The nucleosides were examined, but found inactive against the replication of HIV-1(IIIB) in cell culture, while they were toxic for the cells at a 50% cytotoxic concentration ranging from 31 to >125 μg/ml. But measurements of the inhibitory effects against HIV-1 integrase enzymatic activity showed an interesting activity for compound8c.

  利用微波辐射从氟苯胺开始合成了六种氟喹诺醇核苷。在大多数情况下，微波应用在时间和产率上表现出优势，尤其是对羧基喹诺酮酯3a-3c的一步脱羧和Vorbrüggen糖基化。前者导致了新型氟喹诺糖核苷8a-8c的产生。晶体结构中的化合物8c显示了C3'-endo和反式构象。这些核苷被检测，但在细胞培养中对HIV-1(IIIB)复制无活性，而它们在50%细胞毒性浓度范围内对细胞有毒性，浓度范围从31到>125 μg/ml。但对HIV-1整合酶酶活性的抑制效果的测量显示了化合物8c的有趣活性。