dimethyl 2-(2-nitrobenzylidene)malonate | 65974-52-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: dimethyl 2-(2-nitrobenzylidene)malonate
• 英文别名: dimethyl 2-[(2-nitrophenyl)methylidene]malonate；Dimethyl 2-[(2-nitrophenyl)methylidene]propanedioate
• CAS: 65974-52-9
• 化学式: C₁₂H₁₁NO₆
• mdl: MFCD28160698
• 分子量: 265.222
• InChiKey: LKLMASCOTOBEMT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

制备方法与用途

NCI126224 是一种TLR4信号传导抑制剂，在纳摩尔至低微摩尔范围内能有效抑制LPS诱导的NF-κB、TNF-α、IL-1β和NO的产生。因此，NCI126224 可用于炎症性疾病的科研研究。

反应信息

• 作为反应物：
  描述：

  dimethyl 2-(2-nitrobenzylidene)malonate 在 potassium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 16.0h， 以52%的产率得到3-(2-nitrophenyl)-2-carboxy-2-propenoic acid
  参考文献：
  名称：

  Selection, synthesis, and anti-inflammatory evaluation of the arylidene malonate derivatives as TLR4 signaling inhibitors

  摘要：

  Inhibition of TLR4 signaling is an important therapeutic strategy for intervention in the etiology of several pro-inflammatory diseases. There has been intensive research in recent years aiming to explore this strategy, and identify small molecule inhibitors of the TLR4 pathway. However, the recent failure of a number of advanced drug candidates targeting TLR4 signaling (e.g., TAK242 and Eritoran) prompted us to continue the search for novel chemical scaffolds to inhibit this critical inflammatory response pathway. Here we report the identification of a group of new TLR4 signaling inhibitors through a cell-based screening. A series of arylidene malonate analogs were synthesized and assayed in murine macrophages for their inhibitory activity against LPS-induced nitric oxide (NO) production. The lead compound 1 (NCI126224) was found to suppress LPS-induced production of nuclear factor-kappaB (NF-kappa B), tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), and nitric oxide (NO) in the nanomolar-low micromolar range. Taken together, this study demonstrates that 1 is a promising potential therapeutic candidate for various inflammatory diseases. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.08.022
• 作为产物：
  描述：

  邻硝基苯甲醛 、 丙二酸二甲酯 在 哌啶 、 苯甲酸 作用下， 以 苯 为溶剂， 生成 dimethyl 2-(2-nitrobenzylidene)malonate
  参考文献：
  名称：

  通过烯胺-金属路易斯酸双功能催化，酮与丙二酸丙二酸酯和丙二烯基丙二酸酯的不对称迈克尔加成反应

  摘要：

  新型的烯胺金属路易斯酸双功能催化剂已成功地用于酮与亚烷基丙二酸酯的不对称迈克尔加成反应，具有出色的立体选择性（高达99％ee和> 99：1 dr）。还实现了酮向烯丙基丙二酸酯的不对称迈克尔加成。

  DOI：

  10.1021/jo301070s

文献信息

• The chemoselective reduction of nitro compounds: scope of the electrochemical method
  作者：JM Chapuzet、R Labrecque、M Lavoie、E Martel、J Lessard

  DOI：10.1051/jcp/1996930601

  日期：——

  The selective electrohydrogenation of nitro aliphatic and nitro aromatic functional groups in molecules containing other groups that are easy to hydrogenate (activated double bond, carbon-iodine bond, nitrile,) has been sucessfully carried out in slightly acidic (pH = 3) or neutral (pH = 5-6) methanol-water solutions at Devarda copper and Raney cobalt electrodes. The electrochemical synthesis of a quinolone 15 and a quinoxaline 18 is also reported. Preliminary results on the preparative electroreduction of 5-nitroindole 21 on Hg in aqueous methanol with HBr as supporting electrolyte are presented and dicussed for the first time.

  在含有其他易氢化基团（活化双键、碳-碘键、氰基）的分子中，对硝基脂肪族和硝基芳香族官能团的选择性电氢化已在微酸性（pH = 3）或中性（pH = 5-6）的甲醇-水溶液中，在德尔瓦铜和拉尼钴电极上成功进行。本文还报道了喹诺酮15和喹喉18的电化学合成。首次介绍了在含氢溴酸的甲醇水溶液中，在汞上进行5-硝基吲哚21的制备电还原的初步结果，并进行了讨论。
• Amine compounds, their production and use
  申请人：Takeda Chemical Industries, Ltd.

  公开号：US06329389B1

  公开（公告）日：2001-12-11

  The present invention provides a compound of the formula: wherein Ar represents an aromatic group which may be substituted; X represents methylene, S, SO, SO2 or CO; Y represents a spacer having a main chain of 2 to 5 atoms; n represents an integer of 1 to 5; i) R1 and R2 each represents a hydrogen atom or a lower alkyl which may be substituted, ii) R1 and R2 form, taken together with the adjacent nitrogen atom, a nitrogen-containing heterocyclic ring which may be substituted, or iii) R1 or R2 together with —(CH2)n—N═ form, bonded to a component atom of Ring B, a spiro-ring which may be substituted; Ring A represents an aromatic ring which may be substituted; Ring B represents a 4- to 7-membered nitrogen-containing non-aromatic ring which may be further substituted by alkyl or acyl, with a proviso that X represents S, SO, SO2 or CO when Ring A has as a substituent a group represented by the formula: —NHCOR11 where R11 represents alkyl, alkoxyalkyl, alkylthioalkyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl or a group represented by the formula: —NHR12 where R12 represents alkyl, cycloalkyl, cycloalkylalkyl, aryl or arylalkyl, or a salt thereof; which has an excellent somatostatin receptor binding inhibition action.

  本发明提供了一种化合物，其化学式如下： 其中Ar代表可能被取代的芳香基团； X代表亚甲基、S、SO、SO2或CO； Y代表具有2到5个原子的主链的间隔物； n代表1到5的整数； i）R1和R2分别代表氢原子或可能被取代的较低烷基， ii）R1和R2与相邻的氮原子一起形成可能被取代的含氮杂环环，或 iii）R1或R2与—(CH2)n—N═一起形成，与环B的一个组分原子结合，可能被取代的螺环； 环A代表可能被取代的芳香环； 环B代表可能被烷基或酰基进一步取代的4到7成员的含氮非芳香环， 但有一个条件是，当环A具有由下式表示的基团作为取代基时： —NHCOR11 其中R11代表烷基、烷氧基烷基、烷硫基烷基、环烷基、环烷基烷基、芳基、芳基烷基或由下式表示的基团： —NHR12 其中R12代表烷基、环烷基、环烷基烷基、芳基或芳基烷基，或其盐；具有优异的生长抑素受体结合抑制作用。
• 喹啉酮类化合物及其制备方法和用途
  申请人：复旦大学

  公开号：CN106146464A

  公开（公告）日：2016-11-23

  本发明属药物合成领域，涉及一种新型的喹啉酮类化合物，及其制备方法和用途。本发明经生物实验结果表明，所述的喹啉酮类化合物，对肝细胞生长因子受体(c-met)具有良好的抑制活性，可用作制备防治与c-met相关的疾病的药物，特别是制备防治与c-met相关的癌症的药物；所述的喹啉酮类化合物化学式如下通式I所示，式中取代基如说明书所定义。
• Bicyclic 1-Hydroxy-2-oxo-1,2-dihydropyridine-3-carboxamide-Containing HIV-1 Integrase Inhibitors Having High Antiviral Potency against Cells Harboring Raltegravir-Resistant Integrase Mutants
  作者：Xue Zhi Zhao、Steven J. Smith、Mathieu Métifiot、Barry C. Johnson、Christophe Marchand、Yves Pommier、Stephen H. Hughes、Terrence R. Burke

  DOI：10.1021/jm401902n

  日期：2014.2.27

  the identification of noncytotoxic inhibitors that exhibited single digit nanomolar EC50 values against HIV-1 vectors harboring wild-type IN in cell-based assays. Importantly, some of these new inhibitors retain greater antiviral efficacy compared to that of RAL when tested against a panel of IN mutants that included Y143R, N155H, G140S/Q148H, G118R, and E138K/Q148K.

  整合酶 (IN) 抑制剂是为治疗 HIV-1 感染而开发的最新一类抗逆转录病毒药物。Merck 的 Raltegravir (RAL)（2007 年 10 月）和 Gilead 的 Elvitegravir（EVG）（2012 年 8 月）作为 IN 链转移抑制剂 (INSTI)，是首批获得 FDA 批准的抗 IN 药物。然而，该病毒对RAL和EVG均产生耐药性，并且对这两种药物存在广泛的交叉耐药性。需要新的“第二代” INSTI 对 IN 的 RAL 和 EVG 抗性菌株具有更大的功效。FDA 最近批准了第一代第二代 INSTI，即 GSK 的 Dolutegravir (DTG)（2013 年 8 月）。我们当前的文章描述了一系列 1,8-dihydroxy-2-oxo-1,2-dihydroquinoline-3-carboxamides、1,4-dihydroxy-2-oxo-1,2-dihydro
• Highly Enantioselective Michael Addition of Ketone to Alkylidene Malonates Catalyzed by Binaphthyl Sulfonimides in Water
  作者：Shengjian Jia、Chunhua Luo、Daming Du

  DOI：10.1002/cjoc.201200910

  日期：2012.11

  Binaphthyl sulfonimides have been developed to catalyze the asymmetric Michael addition of ketone to alkylidene malonates, affording the corresponding Michael products in good to high yields (up to 98%) with good to excellent diastereoselectivity (up to 99:1 dr) and enantioselectivity (up to 92% ee) under mild conditions using environmentally benign water as the solvent.

  已开发出联萘磺酰亚胺来催化酮向亚烷基丙二酸酯的不对称迈克尔加成反应，从而以高至高收率（高达98％）提供相应的迈克尔产品，非对映选择性（高达99：1 dr）和对映选择性（高达至92％ee）在温和条件下使用环境温和的水作为溶剂。