二乙基2-[[(2-硝基苯基)氨基]亚甲基]丙二酸酯 | 7255-58-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 二乙基2-[[(2-硝基苯基)氨基]亚甲基]丙二酸酯
• 中文别名: 2-(((2-硝基苯基)氨基)亚甲基)丙二酸二乙酯
• 英文名称: <<(2-nitropenyl)amino>methylene>propanedioic acid diethyl ester
• 英文别名: 2-[(2-nitrophenylamino)-methylene]-malonic acid diethyl ester；diethyl 2-(((2-nitrophenyl)amino)methylene)malonate；diethyl 2-((2-nitrophenylamino)methylene)malonate；(2-nitro-anilinomethylene)-malonic acid diethyl ester；(2-Nitro-anilinomethylen)-malonsaeure-diaethylester；2-[(2-nitro-phenylamino)-methylene]-malonic acid diethyl ester；diethyl 2-[(2-nitroanilino)methylidene]propanedioate
• CAS: 7255-58-5
• 化学式: C₁₄H₁₆N₂O₆
• 分子量: 308.291
• InChiKey: JTGABQDBMSKAOX-UHFFFAOYSA-N

物化性质

• 熔点：
  100-101 °C
• 沸点：
  395.7±42.0 °C(Predicted)
• 密度：
  1.302±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  二乙基2-[[(2-硝基苯基)氨基]亚甲基]丙二酸酯 在 palladium on activated charcoal 氢气 作用下， 以 溶剂黄146 为溶剂， 240.0 ℃ 、344.73 kPa 条件下， 反应 20.0h， 生成 3-methyl-6-oxo-6H-imidazo(4,5,1-ij)quinoline-5-carboxylic acid ethyl ester
  参考文献：
  名称：

  Synthesis and antiallergic activity of some quinolinones and imidazoquinolinones

  摘要：

  A group of 1,4-dihydro-4-oxoquinoline-2- and -3-carboxylic acid esters with nitrogen functionality at the 8-position was synthesized, and 6-oxo-6H-imidazo[4,5,1-ij]quinoline-4- and -5-carboxylic acid esters were elaborated from these. Several of the compounds displayed activity in the rat passive cutaneous anaphylaxis (PCA) test for antiallergic activity. However, PCA activity in this series was accompanied by rat toxicity, as measured by a decrease in percent of normal weight gain over a 2-week period, following a single oral dose.

  DOI：

  10.1021/jm00381a007
• 作为产物：
  描述：

  2-硝基苯胺 、 乙氧基甲叉丙二酸二乙酯 以 甲苯 为溶剂， 反应 3.0h， 以92%的产率得到二乙基2-[[(2-硝基苯基)氨基]亚甲基]丙二酸酯
  参考文献：
  名称：

  通过非共价相互作用辅助二乙基芳基氨基亚甲基丙二酸酯 (DAM) 衍生物超分子组装形成的洞察

  摘要：

  摘要 通过单晶X射线衍射研究了2-(((芳基)氨基)亚甲基)丙二酸二乙酯(DAM)的四种衍生物的晶体结构。发现所有四种衍生物的分子结构都处于共面构象。对四种衍生物的分子构象的详细分析揭示了存在常见的强分子内 N–H⋯O 氢键，形成图集基序 S11 (6) 的环。这里分析了氯和硝基取代对其氢键相对强度的影响。特别是，在化合物 1 中，观察到 -NO2 和 N-H 之间额外的分子内氢键，导致形成另一个六元螯合环。另一方面，在化合物 3 的情况下，我们在此类化合物中首次观察到 I 型 Cl⋯Cl 相互作用。此外，已生成 Hirshfeld 曲面，该曲面用 dnorm 形状指数和弯曲度进行映射，以总结弱相互作用并检查所有四种衍生物中的分子形状。硝基（1 和 2）和氯（3 和 4）取代对 C⋯H、N⋯O 和 C⋯O 相互作用的影响在分子轮廓和 2D 指纹图中突出显示。

  DOI：

  10.1016/j.molstruc.2019.04.114

文献信息

• [EN] QUINOLINE DERIVATIVES AS CASPASE-3 INHIBITOR, PREPARATION FOR PRODUCING THE SAME AND PHARMACEUTICAL COMPOSITION COMPRISING THE SAME<br/>[FR] DERIVES DE LA QUINOLINE INHIBITEURS DE LA CASPASE-3, PREPARATION SERVANT A LES OBTENIR, ET PREPARATIONS PHARMACEUTIQUES LES COMPRENANT
  申请人：YUNGJIN PHARMACEUTICAL CO LTD

  公开号：WO2003093240A1

  公开（公告）日：2003-11-13

  The present invention relates to new quinoline derivatives of formula (1) or their pharmaceutically acceptable salts with caspase-3 inhibitory activity and their preparation methods, wherein R2 is H; halogen; C1-6 alkyl; C 1-6 alkoxy; C1-6 alkoxyalkyl; or C3-6 cycloalkyl; R1 is formula (a); -CN; or formula (b); R is H; C6-14 aryl unsubstituted or substituted by halogen, C1-6 alkyl, C1-6 alkoxy or amino; 5 - 15 membered heterocyclic group unsubstituted or substituted by halogen, C1-6 alkyl, C1-6 alkoxy or amino; or -(CH2)n-CHR4R5. The present invention relates to a pharmaceutical composition for treating caspase-associated diseases by inhibiting the activity of caspase-3 which comprises the compound of formula (1) or its pharmaceutically acceptable salt.

  本发明涉及公式（1）的新喹啉衍生物或其与caspase-3抑制活性有关的药用盐，以及其制备方法，其中R2为H；卤素；C1-6烷基；C1-6烷氧基；C1-6烷氧基烷基；或C3-6环烷基；R1为公式（a）；-CN；或公式（b）；R为H；C6-14芳基，未取代或取代的，取代基为卤素，C1-6烷基，C1-6烷氧基或氨基；5-15成员的杂环基，未取代或取代，取代基为卤素，C1-6烷基，C1-6烷氧基或氨基；或-(CH2)n-CHR4R5。本发明涉及一种治疗caspase相关疾病的药物组合物，通过抑制caspase-3的活性，其中包括公式（1）的化合物或其药用盐。
• Lewis Acid Mediated Selective Monohydrolysis of Geminal Diesters: Synthesis of Functionalized Malonic Acid Half Esters
  作者：Andivelu Ilangovan、Rajendran Kumar、Mahabir Kaushik

  DOI：10.1055/s-0031-1290449

  日期：2012.9

  Geminal diesters, N-alkyl/aryl-2,2-bis(ethoxycarbonyl)vinylamines, were found to undergo selective hydrolysis in the presence of BF3·OEt2 at room temperature to give the corresponding half esters. Neighboring group participation by nitrogen in the hydrolysis was observed. This method is useful for the preparation of highly functionalized malonic acid half esters.

  发现孪生二酯，N-烷基/芳基-2,2-双(乙氧基羰基)乙烯基胺，在BF3·OEt2存在下在室温下经历选择性水解，得到相应的半酯。观察到氮参与水解的相邻基团。该方法可用于制备高度官能化的丙二酸半酯。
• Phenanthroline derivatives
  申请人：Zeneca Limited

  公开号：US05916898A1

  公开（公告）日：1999-06-29

  The present invention provides a phenanthroline derivative of formula (I) ##STR1## wherein, for example, R.sup.1 is hydrogen, carboxy, cyano, nitro, (1-4C)alkyl, (1-6C)alkoxycarbonyl, (1-4C)alkylamino, (2-4C)alkanoyl, (1-4C)alkoxy-(2-4C)alkoxy-(2-4C)alkoxycarbonyl or N-\x9bamino-(2-8C)alkyl!carbamoyl; R.sup.2 is, for example, hydrogen, carboxy, (1-6C)alkoxycarbonyl, carbamoyl, N-(1-8C)alkylcarbamoyl, N,N-di-(1-8C)alkylcarbamoyl, N-(1-4C)alkylcyclohexylcarbamoyl, 1,2,3,4-tetrahydro-isoquinolin-2-ylcarbonyl or N,N-\x9bdi-(1-4C)alkyl!thiocarbamoyl; R.sup.3 and R.sup.4, which may be the same or different, are, for example, hydrogen or halo; and R.sup.5 is, for example, hydrogen, di-(1-4C)alkylamino or halo; or a pharmaceutically-acceptable salt thereof. The invention further provides pharmaceutical compositions comprising phenanthroline derivatives, processes for making the same and their use in producing an anti-fibroproliferative effect.

  本发明提供了一种公式（I）的菲啰啉衍生物 ##STR1## 其中，例如，R.sup.1是氢，羧基，氰基，硝基，（1-4C）烷基，（1-6C）烷氧羰基，（1-4C）烷基氨基，（2-4C）烷酰基，（1-4C）烷氧基-（2-4C）烷氧基-（2-4C）烷氧羰基或N-\x9b氨基-(2-8C)烷基!羰基；R.sup.2是，例如，氢，羧基，（1-6C）烷氧羰基，氨基羰基，N-(1-8C)烷基氨基羰基，N,N-双（1-8C)烷基氨基羰基，N-(1-4C)烷基环己基氨基羰基，1,2,3,4-四氢-异喹啉-2-基羰基或N,N-\x9b双（1-4C)烷基!硫氨基羰基；R.sup.3和R.sup.4，可以相同也可以不同，例如，是氢或卤素；而R.sup.5是，例如，氢，双（1-4C)烷基氨基或卤素；或其药学上可接受的盐。本发明还提供了包括菲啰啉衍生物的药物组合物，制备这些药物的方法以及它们在产生抗纤维增殖效应中的应用。
• Quinoline derivatives as caspase-3 inhibitor, preparation for producing the same and pharmaceutical composition comprising the same
  申请人：——

  公开号：US20040260094A1

  公开（公告）日：2004-12-23

  The present invention relates to new quinoline derivatives of formula (1) or their pharmaceutically acceptable salts with caspase-3 inhibitory activity and their preparation methods, wherein R 2 is H; halogen; C 1-6 alkyl; C 1-6 alkoxy; C 1-6 alkoxyalkyl; or C 3-6 cycloalkyl; R 1 is formula (a); —CN; or formula (b); R is H; C 6-14 aryl unsubstituted or substituted by halogen, C 1-6 alkyl, C 1-6 alkoxy or amino; 5-15 membered heterocyclic group unsubstituted or substituted by halogen, C 1-6 alkyl, C 1-6 alkoxy or amino; or —(CH 2 ) n —CHR 4 R 5 . The present invention relates to a pharmaceutical composition for treating caspase-associated diseases by inhibiting the activity of caspase-3 which comprises the compound of formula (1) or its pharmaceutically acceptable salt. 1

  本发明涉及式（1）的新喹啉衍生物或其药学上可接受的盐，具有caspase-3抑制活性及其制备方法，其中R2为H; 卤素; C1-6烷基; C1-6烷氧基; C1-6烷氧基烷基; 或C3-6环烷基; R1为式（a）; —CN; 或式（b）; R为H; C6-14芳基未取代或取代卤素，C1-6烷基，C1-6烷氧基或氨基; 5-15成员的杂环基未取代或取代卤素，C1-6烷基，C1-6烷氧基或氨基; 或—（CH2）n—CHR4R5。本发明涉及一种用于通过抑制caspase-3活性治疗caspase相关疾病的制剂，包括式（1）的化合物或其药学上可接受的盐。
• Ethene derivatives
  申请人：MAY & BAKER LIMITED

  公开号：EP0174832A2

  公开（公告）日：1986-03-19

  Ethene derivatives of the general formula: wherein R5 represents a heterocyclyl group, containing 1, 2 or 3 rings and one or more heteroatoms selected from nitrogen, oxygen, sulphur and selenium atoms, which is unsubstituted or substituted by one or more substituents R8 [which may be the same or different and each represents a halogen atom or an amino, carboxy, cyano, nitro, hydroxy, oxo, formyl, trifluoromethyl, aryl, aryloxy, arylthio, benzyloxycarbonylamino, sulphamoyl, tetrazol-5-yl, carbamoyl, thiocarbamoyl, arylcarbamoyl or aroyl group, or a straight-or branched-chain alkyl group containing from 1 to 10 carbon atoms, or a straight- or branched-chain alkoxy, alkylthio, alkylsulphinyl, alkylsulphonyl, alkylamino, alkylsulphamoyl, arylalkyl or arylalkoxy group containing from 1 to 10 carbon atoms in the alkyl moiety, a straight- or branched-chain alkanoyl, alkoxycarbonyl, alkoxycarbonylamino, alkylcarbamoyl or alkanoylamino group containing from 2 to 6 carbon atoms, an N-benzyloxycarbonyl-N-alkylamino group wherein the alkylamino moiety is straight- or branched-chain and contains from 1 to 6 carbon atoms, or a dialkylsulphamoyl, dialkylamino or dialkylcarbamoyl group wherein the alkyl moieties may be straight or branched and may each contain from 1 to 6 carbon atoms and may be linked together to form a ring, or a group of the formula -CR4=CR2R3, or an aryl group which is unsubstituted or substituted by one or more substituents RS (as hereinbefore defined), or a heterocyclylalkyl or arylalkyl group wherein the heterocyclyl or aryl moiety is as hereinbefore defined and the alkyl moiety is straight- or branched-chain and contains 1 or 2 carbons atoms, and R1 represents a group of the general formula: wherein R6 represents a hydrogen atom or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be substituted by one or more substituents RS (as hereinbefore defined) or an aryl group which may be substituted by one or more substituents R8 (as hereinbefore defined), or R5 represents a quinonoidal group R7 derived from a nitrogen-containing heterocyclyl group within the definition of R5 as hereinbefore defined, bearing on said ring-nitrogen atom a substituent selected from straight- and branched-chain alkyl groups containing from 1 to 6 carbon atoms which may be substituted by one or more substituents RS (as hereinbefore defined), and aryl groups which may be substituted by one or more substituents RS (as hereinbefore defined), and R1 represents an atom =N-, R4 represents a hydrogen atom or a straight- or branched-chain alkoxy or alkylthio group containing from 1 to 6 carbon atoms, a trifluoromethyl group or a straight- or branched-chain alkyl group containing from 1 to 6 carbon atoms which may be substituted by one or more substituents R8 (as hereinbefore defined), or an aryl group which may be substituted by one or more substituents R8 (as hereinbefore defined), R2 represents a cyano or formyl group, a straight- or branched-chain alkoxycarbonyl or alkylsulphonyl group containing up to 6 carbons, or a dialkylcarbamoyl or dialkylthiocarbamoyl group wherein the alkyl groups may be the same or different and each may be straight or branched and each contains from 1 to 6 carbon atoms, or an aryloxycarbonyl, arylsulphinyl or arylsulphonyl group wherein the aryl moiety may be substituted by one or more substituents R8 (as hereinbefore defined), R3 represents a group within the definition of R2 or a hydrogen atom or a nitro group or an aryl or aroyl group which may be substituted by one or more substituents R8 (as hereinbefore defined) or a straight- or branched-chain alkanoyl group containing up to 6 carbon atoms, and m and n each represents 1 or 2, and pharmaceutically acceptable salts thereof, with the provisos that the following classes of compounds are excluded:- (i) compounds of formula I wherein R5 represents a pyridyl group which is unsubstituted or substituted by one or more substituents R9 which may be the same or different and each represents a group within the definition of Re other than oxo, straight- or branched-chain alkyl containing from 7 to 10 carbon atoms, straight- or branched-chain alkoxy, alkylthio, alkylsulphonyl, alkylamino, alkylsulphamoyl or arylalkyl containing from 7 to 10 carbon atoms in the alkyl moiety, straight- or branched-chain alkylsulphinyl or arylalkoxy containing from 1 to 10 carbon atoms in the alkyl moiety, or a group -CR4=CR2R3 as hereinbefore defined, R2 and R3 may be the same or different and each represents a phenylsulphonyl group which may be unsubstituted or substituted by one or more substituents R9 (as hereinbefore defined), R' represents a group of formula II, R4 and R6 represent hydrogen atoms and m and n both represent 1; (ii) compounds of formula I wherein R5 represents a 5-halogenopyrid-2-yl group, R2 and R3 both represent cyano groups, R1 represents a group of formula II, R4 and R° represent hydrogen atoms and m and n both represent 1; and (iii) compounds of formula I wherein R5 represents a 1,2,4-triazolo[4,8-a]-quinoline group which is unsubstituted or substituted by one or more substituents R10 which may be the same or different and each represents a group within the definition of R9 or a straight- or branched-chain alkylsulphinyl group containing from 1 to 6 carbon atoms, R2 and R3 may be the same or different and each represents a cyano group, a straight- or branched-chain alkoxycarbonyl group containing from 2 to 6 carbon atoms, or a phenylsulphonyl group which may be unsubstituted or substituted by one or more substituents R10 (as hereinbefore defined), R' represents a group of formula II, R4 and R6 represent hydrogen atoms and m and n both represent 1, possess useful pharmacological properties.

  以下是对文本的中文翻译： **丙烯衍生物的通式**： 其中，R5代表一个杂环基，包含1、2或3个环，并且含有1个或多个选自氮、氧、硫和硒原子的杂原子，该杂环基可以是未取代的，或被一个或多个R8取代基取代（R8可以相同或不同，每个R8代表一个卤素原子；或者一个氨基、羧基、氰基、硝基、羟基、羰基、甲酰基、三氟甲基、芳基、芳氧基、芳硫基、苄氧羰基氨基、硫脲基、5-四唑基、羰基氨基、硫代羰基氨基、芳基羰基氨基或芳酰基；或者一个直链或支链烷基，含有1至10个碳原子；或者一个直链或支链烷氧基、烷硫基、烷亚砜基、烷砜基、烷氨基、烷硫脲基、芳基烷基或芳基烷氧基，其中烷基部分含有1至10个碳原子；或者一个直链或支链烷酰基、烷氧基羰基、烷氧基羰基氨基、烷基羰基氨基或烷酰基氨基，含有2至6个碳原子；或者一个N-苄氧羰基-N-烷基氨基，其中烷基氨基部分为直链或支链，含有1至6个碳原子；或者一个二烷基硫脲基、二烷基氨基或二烷基羰基氨基，其中烷基部分可以为直链或支链，每个烷基部分含有1至6个碳原子，且烷基部分可以彼此连接形成一个环；或者一个通式为-CR4=CR2R3的基团；或者一个未取代的芳基，或被一个或多个R8取代基取代的芳基；或者一个杂环基烷基或芳基烷基，其中杂环基或芳基部分如前所定义，烷基部分为直链或支链，含有1或2个碳原子）。 R1代表一个通式为的基团： 其中，R6代表一个氢原子；或一个直链或支链烷基，含有1至6个碳原子，该烷基可以被一个或多个R8取代基取代（如前所定义）；或一个芳基，可以被一个或多个R8取代基取代（如前所定义）。 此外，R5还可以代表一个由含氮杂环基衍生而来的醌状基团R7，该杂环基如前所定义的R5，其中环氮原子上取代有一个选自以下的基团：直链或支链烷基，含有1至6个碳原子，该烷基可以被一个或多个R8取代基取代（如前所定义）；或一个芳基，可以被一个或多个R8取代基取代（如前所定义）。 R1代表一个=NH原子；R4代表一个氢原子，或一个直链或支链烷氧基、烷硫基，含有1至6个碳原子；或一个三氟甲基基团；或一个直链或支链烷基，含有1至6个碳原子，该烷基可以被一个或多个R8取代基取代（如前所定义）；或一个芳基，可以被一个或多个R8取代基取代（如前所定义）。 R2代表一个氰基或甲酰基；或一个直链或支链烷氧基羰基或烷硫基，含有不超过6个碳原子；或一个二烷基羰基氨基或二烷基硫代羰基氨基，其中两个烷基可以相同或不同，每个烷基为直链或支链，含有1至6个碳原子；或一个芳氧基羰基、芳硫基或芳硫基羰基，其中芳基部分可以被一个或多个R8取代基取代（如前所定义）。 R3代表一个与R2定义范围内的基团，或一个氢原子；或一个硝基；或一个芳基；或一个芳酰基，可以被一个或多个R8取代基取代（如前所定义）；或一个直链或支链烷酰基，含有不超过6个碳原子。 m和n各自代表1或2。 除以下化合物类别外，上述结构及其药学上可接受的盐类具有有用的药理学性质： (i) 通式为I的化合物，其中R5代表一个吡啶基，该吡啶基可以是未取代的，或被一个或多个R9取代基取代，R9可以相同或不同，每个R9代表一个基团，其定义范围包括：R8（但不包括氧代基、直链或支链烷基，含有7至10个碳原子；直链或支链烷氧基、烷硫基、烷硫基、烷氨基、烷硫脲基、或芳基烷基，其中烷基部分含有7至10个碳原子；直链或支链烷亚砜基，或芳基烷氧基，其中烷基部分含有1至10个碳原子）；或一个如前所定义的-CR4=CR2R3基团。其中，R2和R3可以相同或不同，各自代表一个苯硫基，可以是未取代的，或被一个或多个R9取代基取代（如前所定义）。R’代表一个通式II的基团。R4和R6代表氢原子，m和n均为1。 (ii) 通式为I的化合物，其中R5代表一个5-卤素取代吡啶-2-基，R2和R3均为氰基，R1代表一个通式II的基团，R4和R°代表氢原子，m和n均为1。 (iii) 通式为I的化合物，其中R5代表一个1,2,4-三唑[4,8-a]-喹啉基，该基团可以是未取代的，或被一个或多个R10取代基取代，R10可以相同或不同，每个R10代表一个基团，其定义范围包括：R9（如前所定义），或一个直链或支链烷亚砜基，含有1至6个碳原子。R2和R3可以相同或不同，各自代表一个氰基、一个直链或支链烷氧基羰基（含有2至6个碳原子），或一个苯硫基，可以是未取代的，或被一个或多个R10取代基取代（如前所定义）。R’代表一个通式II的基团。R4和R6代表氢原子，m和n均为1。 上述化合物在排除了特定结构后，具有有用的药理学性质。