4-nitro-2-(phenoxymethyl)benzoic acid | 915034-91-2

• 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: 4-nitro-2-(phenoxymethyl)benzoic acid
• 英文别名: 4-Nitro-2-phenoxymethylbenzoic Acid
• CAS: 915034-91-2
• 化学式: C₁₄H₁₁NO₅
• 分子量: 273.245
• InChiKey: NTPGBUADUKGSHU-UHFFFAOYSA-N

物化性质

• 熔点：
  180 °C
• 沸点：
  481.0±35.0 °C(Predicted)
• 密度：
  1.376±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  92.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-nitro-2-(phenoxymethyl)benzoic acid 在 sodium hydride 、 tin(ll) chloride 作用下， 以 环丁砜 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 8-(2-fluoro-4-nitrophenylamino)-6H-dibenzo[b,e]oxepin-11-one
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Phenylamino-Substituted 6,11-Dihydro-dibenzo[b,e]oxepin-11-ones and Dibenzo[a,d]cycloheptan-5-ones:  Novel p38 MAP Kinase Inhibitors

  摘要：

  The pathogenesis of chronic inflammatory diseases is promoted by various pro-inflammatory cytokines. p38 MAP kinase seems to be a valid target as it controls proinflammatory cytokine levels on both transcriptional and translational levels. Starting from benzophenone-type inhibitors, a rigidisation strategy lead to 3-amino-6,11-dihydro-dibenzo[b,e]thiepin-11-one, phenylamino-substituted 6,11-dihydro-dibenzo[b,e]oxepin-11-ones, and dibenzo[a,d]cyclohepten-5-ones. Synthesis, p38 inhibition, and CYP-inhibition of selected compounds are described.

  DOI：

  10.1021/jm061072p
• 作为产物：
  描述：

  2-溴甲基-4-硝基苯甲酸甲酯 在 potassium phosphate 、 水 、 potassium hydroxide 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 10.0h， 生成 4-nitro-2-(phenoxymethyl)benzoic acid
  参考文献：
  名称：

  铁（II）促进具有生物活性的二苯并[ b，e ] oxepin-11（6H）-one衍生物的直接合成。多塞平的简短合成

  摘要：

  通过直接的分子内邻位酰化反应，从容易获得的2-（苯氧基甲基）苯甲酸中合成了新颖高效的二苯并[ b，e ] oxepin-11（6H）-酮。该方法利用了由可持续的FeCl 2和Cl 2 CHOCH 3作为关键成分的新开发的协作系统。该方法与多种官能团兼容，具有良好的收率和极高的区域选择性。新方案的合成应用扩展到了已知的三环药物多塞平的合成，以及一个基于奥塞平的衍生物的小型文库。首次获得的二苯并[ b，e对] oxepinone衍生物在自由生活的线虫秀丽隐杆线虫上的生物学活性进行了评估，以此作为驱虫药发现的一种有效且具有成本效益的模型系统。

  DOI：

  10.1016/j.tet.2017.03.085

文献信息

• Dibenzocycloheptane compounds and pharmaceuticals containing these compounds
  申请人：Laufer Stefan

  公开号：US20090105327A1

  公开（公告）日：2009-04-23

  The present invention relates to compounds of the formula I in which R1, R2, R3, R4, X and Y have the meanings indicated in the description. These compounds have immunomodulating effects, as well as an inhibiting or regulating effect on the release of IL-1β and/or TNF-α. They can therefore be used for the treatment of diseases associated with a disturbance of the immune system.

  本发明涉及式I的化合物，其中R1、R2、R3、R4、X和Y具有描述中所示的含义。这些化合物具有免疫调节作用，以及对IL-1β和/或TNF-α的释放具有抑制或调节作用。因此，它们可用于治疗与免疫系统紊乱相关的疾病。
• WO2006/120010
  申请人：——

  公开号：——

  公开（公告）日：——
• DIBENZOCYCLOHEPTANVERBINDUNGEN UND PHARMAZEUTISCHE MITTEL, WELCHE DIESE VERBINDUNGEN ENTHALTEN
  申请人：MERCKLE GMBH

  公开号：EP1881968A2

  公开（公告）日：2008-01-30
• [DE] DIBENZOCYCLOHEPTANVERBINDUNGEN UND PHARMAZEUTISCHE MITTEL, WELCHE DIESE VERBINDUNGEN ENTHALTEN<br/>[EN] DIBENZOCYCLOHEPTANE COMPOUNDS AND PHARMACEUTICALS CONTAINING THESE COMPOUNDS<br/>[FR] DIBENZOCYCLOHEPTANES ET AGENTS PHARMACEUTIQUES CONTENANT CES COMPOSES
  申请人：MERCKLE GMBH

  公开号：WO2006120010A2

  公开（公告）日：2006-11-16

  [EN] The present invention relates to compounds of formula (I), in which R1, R2, R3, R4, X and Y have the meanings indicated in the description. These compounds have immuno-modulating effects, as well as an inhibiting or regulating effect on the release of IL-1ß and/or TNF-a. They can therefore be used for the treatment of diseases associated with a disturbance of the immune system.
  [FR] La présente invention concerne des composés de formule (I), dans laquelle R1, R2, R3, R4, X et Y ont les significations indiquées dans la description. Ces composés possèdent une action immunomodulatrice et un effet d'inhibition ou de régulation de la libération de IL-1ß et/ou TNF-a. Ils peuvent donc être utilisés pour traiter des maladies liées à un trouble du système immunitaire.
  [DE] Die vorliegende Erfindung betrifft Verbindungen der Formel (I), worin R1, R2, R3, R4, X und Y die in der Beschreibung angegebenen Bedeutungen besitzen. Die Verbindungen besitzen immunmodulierende und die Freisetzung von IL-1ß und/oder TNF-a inhibierende bzw. regulierende Wirkung. Sie sind daher zur Behandlung von Erkrankungen brauchbar, die im Zusammenhang mit einer Störung des Immunsystems stehen.
  [EN] Dibenzocycloheptane compounds (I) and their salt and solvate and its salts, are new. Dibenzocycloheptane compounds of formula (I) and their salt and solvate and its salts, are new. Either X, Y1 : CH2, O, S, SO, SO2 or NR5; or X-Y1- : -(CH2)2- or -CH=CH-; R1 : H or 1-6C alkyl; R2 : H, halo or 1-4C alkyl-C?=C- (optionally substituted with amino group); R3 : -NH2, phenyl compound of formula (a) or (b), cyclohexane compound of formula (c), -NH-1-6C alkylene-NH2 or halo; either R4 : H, halo or 1-6C alkyl; or CR3R4 : phenyl ring, 5-6 membered aromatic or non-aromatic heterocyclic ring with heteroatom such as N (where the heterocyclic ring is substituted with one or two 1-6C alkyl group or is condensed with a cyclohexyl group); R5, R6 : H or 1-6C alkyl; R7 : H, NH2, mono-1-6C alkyl amino, di-1-6C alkylamino, 1-6C alkyl-CONH-, 1-6C alkyl-NHCONH-, 1-6C alkyl-O-CO-NH-, 1-6C alkyl, 1-6C alkoxy, NO2 or halo; R8 : H, NH2, mono-1-6C alkylamino, di-1-6C alkylamino, 1-6C alkoxy or halo; and R9 : H or NH2. [Image] [Image] - ACTIVITY : Immunosuppressive; Cytostatic; Antiarthritic; Antirheumatic; Litholytic; Antibacterial; Osteopathic; Neuroprotective; Anti-HIV; Virucide; Antidiabetic; Antiinflammatory; Vasotropic; Endocrine-Gen.; Antipsoriatic; Antiarteriosclerotic; Immunomodulator; Nootropic; Cerebroprotective; Antiulcer; Gastrointestinal-Gen.; Cardiovascular-Gen.; Cardiant; Respiratory-Gen.; Hepatotropic; CNS-Gen.; Dermatological. - MECHANISM OF ACTION : Interleukin-1beta inhibitor; Tumor necrosis factor-alpha inhibitor; Interleukin-1beta regulator; Tumor necrosis factor-alpha regulator. The ability of (I) to inhibit interleukin-1beta was tested using biological assays. The results showed that (I) exhibited an IC50 value of 1.8 mu M.
• Design, Synthesis, and Biological Evaluation of Phenylamino-Substituted 6,11-Dihydro-dibenzo[<i>b</i>,<i>e</i>]oxepin-11-ones and Dibenzo[<i>a</i>,<i>d</i>]cycloheptan-5-ones:  Novel p38 MAP Kinase Inhibitors
  作者：Stefan A. Laufer、Gabriele M. Ahrens、Solveigh C. Karcher、Jörg S. Hering、Raimund Niess

  DOI：10.1021/jm061072p

  日期：2006.12.1

  The pathogenesis of chronic inflammatory diseases is promoted by various pro-inflammatory cytokines. p38 MAP kinase seems to be a valid target as it controls proinflammatory cytokine levels on both transcriptional and translational levels. Starting from benzophenone-type inhibitors, a rigidisation strategy lead to 3-amino-6,11-dihydro-dibenzo[b,e]thiepin-11-one, phenylamino-substituted 6,11-dihydro-dibenzo[b,e]oxepin-11-ones, and dibenzo[a,d]cyclohepten-5-ones. Synthesis, p38 inhibition, and CYP-inhibition of selected compounds are described.