methyl 4-methoxy-5-(2-methoxyethoxy)-2-nitrobenzoate | 1146162-35-7

• 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: methyl 4-methoxy-5-(2-methoxyethoxy)-2-nitrobenzoate
• CAS: 1146162-35-7
• 化学式: C₁₂H₁₅NO₇
• 分子量: 285.254
• InChiKey: IPVQZMKCUYDJCB-UHFFFAOYSA-N

物化性质

• 沸点：
  422.4±45.0 °C(Predicted)
• 密度：
  1.259±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  99.8
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 4-methoxy-5-(2-methoxyethoxy)-2-nitrobenzoate 在 甲醇 、 sodium dithionite 、 水 、 溶剂黄146 、 三氯氧磷 作用下， 生成 4-chloro-7-methoxy-6-(2-methoxyethoxy)quinazoline
  参考文献：
  名称：

  4-Quinazolinyloxy-diaryl ureas as novel BRAFV600E inhibitors

  摘要：

  Aryl phenyl ureas with a 4-quinazolinoxy substituent at the meta-position of the phenyl ring are potent inhibitors of mutant and wild type BRAF kinase. Compound 7 (1-(5-tert-butylisoxazol-3-yl)-3-(3-(6,7-dimethoxyquinazolin-4-yloxy) phenyl) urea hydrochloride) exhibits good pharmacokinetic properties in rat and mouse and is efficacious in a mouse tumor xenograft model following oral dosing. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.07.019
• 作为产物：
  描述：

  5-羟基-4-甲氧基-2-硝基苯甲酸甲酯 、 2-氯乙基甲基醚 在 四丁基碘化铵 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 336.5h， 以95%的产率得到methyl 4-methoxy-5-(2-methoxyethoxy)-2-nitrobenzoate
  参考文献：
  名称：

  [EN] THERAPEUTIC OXY-PHENYL-ARYL COMPOUNDS AND THEIR USE
  [FR] COMPOSÉS OXY-PHÉNYL-ARYLES THÉRAPEUTIQUES ET LEUR UTILISATION

  摘要：

  本发明总体涉及治疗化合物领域，更具体地涉及如本文所述的某些氧基苯基芳基化合物（以下简称OPA化合物），其中，抑制检查点激酶2（CHK2）激酶功能。本发明还涉及包含此类化合物的药物组合物，以及使用此类化合物和组合物，在体内外抑制CHK2激酶功能，以及治疗由CHK2介导的疾病和状况，包括通过抑制CHK2激酶功能而改善的疾病和状况，等等，包括诸如癌症等增殖性疾病，可选地与另一剂联合使用，例如，（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）针对微管的药剂；（e）电离辐射。

  公开号：

  WO2009053694A1

文献信息

• Targeted Drug-Formaldehyde Conjugates and Methods of Making and Using the Same
  申请人：Koch H. Tad

  公开号：US20070275911A1

  公开（公告）日：2007-11-29

  The invention provides a prodrug platform technology for improving the therapeutic value of a variety of parent drug compounds by altering and improving drug characteristics such as aqueous solubility, hydrolytic stability, therapeutic index, toxicity profile, pharmacolcinetics and selectivity while allowing the potential for synthetic elaboration. The prodrug platform is particularly well suited for targeting therapeutic drugs, including anti-tumor drugs and antibiotics, to specific receptors on target cells (e.g., cancer cells and bacteria). The platform is a technology for providing an improved, preactivated form of a therapeutic drug, and for optionally targeting such drug to target cells or biological molecules. The invention is broadly applicable to many different therapeutic drugs, as well as to a variety of diseases and conditions, including a variety of forms of cancer and bacterial infections.

  本发明提供了一种前药平台技术，通过改变和改进药物特性，如水溶性、水解稳定性、治疗指数、毒性谱、药代动力学和选择性，从而提高各种原始药物化合物的治疗价值，同时允许潜在的合成扩展。该前药平台特别适用于将治疗药物，包括抗肿瘤药物和抗生素，定向靶向到目标细胞（例如癌细胞和细菌）上的特定受体。该平台是一种提供改进的、预激活形式的治疗药物的技术，并可选择性地将该药物定向到目标细胞或生物分子。本发明广泛适用于许多不同的治疗药物，以及多种癌症和细菌感染等不同疾病和病况。
• Therapeutic Oxy-Phenyl-Aryl Compounds and Their Use
  申请人：Collins Ian

  公开号：US20110201592A1

  公开（公告）日：2011-08-18

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明涉及治疗化合物领域，更具体地涉及某些氧苯基芳基化合物（以下简称OPA化合物），如本文所述，该化合物在其中抑制检查点激酶2（CHK2）激酶功能。本发明还涉及包含这种化合物的制药组合物，以及在体外和体内使用这种化合物和组合物来抑制CHK2激酶功能，并治疗由CHK2介导，通过抑制CHK2激酶功能改善的疾病和病况，包括增殖性疾病，如癌症等，可选择与另一种药物一起使用，例如（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）微管靶向药物；和（e）电离辐射。
• RAF KINASE MODULATOR COMPOUNDS AND METHODS OF USE THEREOF
  申请人：Abraham Sunny

  公开号：US20110118245A1

  公开（公告）日：2011-05-19

  Compounds according to formula (I), compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases. Formula (I): or a pharmaceutically acceptable salt, solvate, clathrate of hydrate thereof, wherein X is O or S(O) t ; R a is O or S.

  提供了按照公式(I)的化合物、组合物和方法，用于调节RAF激酶的活性，包括BRAF激酶，并用于治疗、预防或缓解由RAF激酶介导的一种或多种疾病或障碍的症状。公式(I)：或其药学上可接受的盐、溶剂化合物、包合物或水合物，其中X为O或S(O)t；R为O或S。
• Therapeutic oxy-phenyl-aryl compounds and their use
  申请人：Cancer Research Technology Limited

  公开号：US08324226B2

  公开（公告）日：2012-12-04

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to certain oxy phenyl aryl compounds (referred to herein as OPA compounds), as described herein, which, inter alia, inhibit Checkpoint Kinase 2 (CHK2) kinase function. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit CHK2 kinase function, and in the treatment of diseases and conditions that are mediated by CHK2, that are ameliorated by the inhibition of CHK2 kinase function, etc., including proliferative conditions such as cancer, etc., optionally in combination with another agent, for example, (a) a DNA topoisomerase I or II inhibitor; (b) a DNA damaging agent; (c) an antimetabolite or TS inhibitor; (d) a microtubule targeted agent; and (e) ionising radiation.

  本发明涉及治疗化合物领域，更具体地涉及某些氧代苯基芳基化合物（以下简称OPA化合物），如本文所述，它们可以抑制检查点激酶2（CHK2）激酶功能。本发明还涉及包含这些化合物的制药组合物，以及在体内外使用这些化合物和组合物来抑制CHK2激酶功能，并用于治疗由CHK2介导的疾病和病情，通过抑制CHK2激酶功能而改善的疾病和病情，包括增生性疾病如癌症等，可选择与另一种药物联合使用，例如：（a）DNA拓扑异构酶I或II抑制剂；（b）DNA损伤剂；（c）抗代谢物或TS抑制剂；（d）微管靶向剂；和（e）电离辐射。
• RAF kinase modulator compounds and methods of use thereof
  申请人：Ambit Biosciences Corporation

  公开号：US08969587B2

  公开（公告）日：2015-03-03

  Compounds, compositions and methods are provided for modulating the activity of RAF kinases, including BRAF kinase and for the treatment, prevention, or amelioration of one or more symptoms of disease or disorder mediated by RAF kinases.

  本发明提供了用于调节RAF激酶活性的化合物、组合物和方法，包括BRAF激酶，并用于治疗、预防或改善由RAF激酶介导的一种或多种疾病或障碍的症状。