dimethyl 3-nitrobiphenyl-4-malonate | 100487-83-0

• 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: dimethyl 3-nitrobiphenyl-4-malonate
• 英文别名: dimethyl-3-nitrobiphenyl-4-malonate；dimethyl 2-(2-nitro-4-phenylphenyl)propanedioate
• CAS: 100487-83-0
• 化学式: C₁₇H₁₅NO₆
• 分子量: 329.309
• InChiKey: FSADKQTZVABRCO-UHFFFAOYSA-N

物化性质

• 熔点：
  82-83 °C
• 沸点：
  469.5±45.0 °C(Predicted)
• 密度：
  1.283±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  98.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl 3-nitrobiphenyl-4-malonate 以 二甲基亚砜 为溶剂， 生成 (3-Nitro-biphenyl-4-yl)-acetic acid methyl ester
  参考文献：
  名称：

  一种统一的催化不对称 (4+1) 和 (5+1) 环化策略来获得手性螺环吲哚稠合氧杂环化合物

  摘要：

  在手性相转移催化剂 (PTC) 的存在下，已经实现了羟吲哚与双官能过氧化物的统一催化不对称 ( N +1) ( N =4, 5) 环化反应。这种通用策略利用过氧化物作为独特的双亲电四原子或五原子合成子参与 C−C 和随后与单碳单元亲核试剂的 umpolung C−O 键形成反应，从而提供了一种独特的方法来获得有价值的手性螺吲哚-四氢呋喃和-四氢吡喃在温和条件下具有良好的产率和高对映选择性。进行 DFT 计算以合理化高对映选择性的起源。还证明了所得产物的克级合成和合成效用。

  DOI：

  10.1002/anie.202105282
• 作为产物：
  描述：

  4-溴-1-氟-2-硝基苯 在 四(三苯基膦)钯 、 sodium hydride 、 碳酸氢钠 、 二甲基亚砜 作用下， 以 甲苯 为溶剂， 反应 4.17h， 生成 dimethyl 3-nitrobiphenyl-4-malonate
  参考文献：
  名称：

  Design, Synthesis, and Evaluations of Substituted 3-[(3- or 4-Carboxyethylpyrrol-2-yl)methylidenyl]indolin-2-ones as Inhibitors of VEGF, FGF, and PDGF Receptor Tyrosine Kinases

  摘要：

  Receptor tyrosine kinases (RTKs) have been implicated as therapeutic targets for the treatment of human diseases including cancers, inflammatory diseases, cardiovascular diseases including arterial restenosis, and fibrotic diseases of the lung, liver, and kidney. Three classes of 3-substituted indolin-2-ones containing propionic acid functionality attached to the pyrrole ring at the C-3 position of the core have been identified as catalytic inhibitors of the vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-derived growth factor (PDGF) RTKs. Some of the compounds were found to inhibit the tyrosine kinase activity associated with isolated vascular endothelial growth factor receptor 2 (VEGF-R2) [fetal liver tyrosine kinase 1 (Flk-1)/kinase insert domain-containing receptor (KDR)], fibroblast growth factor receptor (FGF-R), and platelet-derived growth factor receptor (PDGF-R) tyrosine kinase with IC50 values at nanomolar level. Thus, compound 1 showed inhibition against VEGF-R2 (Flk-1/KDR) and FGF-R1 tyrosine kinase activity With IC50 values of 20 and 30 nM, respectively, while compound 16f inhibited the PDGF-R tyrosine kinase activity with IC50 value of 10 nM. Structural models and structure-activity relationship analysis of these compounds for the target receptors are discussed. The cellular activities of these compounds were profiled using cellular proliferation assays as measured by bromodeoxyuridine (BrdU) incorporation. Specific and potent inhibition of cell growth was observed for some of these compounds. These data provide evidence that these compounds can be used to inhibit the function of these target receptors.

  DOI：

  10.1021/jm9904295

文献信息

• 3-heteroarylidene-2-indolinone protein kinase inhibitors
  申请人：Sugen, Inc.

  公开号：US06486185B1

  公开（公告）日：2002-11-26

  The present invention relates to novel 3-heteroarylidene-2-indolinone compounds and physiologically acceptable salts thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

  本发明涉及新颖的3-杂环亚烯基-2-吲哚酮化合物及其生理上可接受的盐，这些化合物调节蛋白激酶的活性，因此预计在预防和治疗蛋白激酶相关的细胞疾病，如癌症方面具有用处。
• Formulations for pharmaceutical agents ionizable as free acids or free bases
  申请人：Shenoy Narmada

  公开号：US06878733B1

  公开（公告）日：2005-04-12

  The present invention features formulations of indolinones which compounds are ionizable as free acids or free bases. The formulation is suitable for parenteral or oral administration, wherein the formulation comprises an ionizable substituted indolinone, and a pharmaceutically acceptable carrier therefor. The term “ionizable substituted indolinone” includes pyrrole substituted 2-indolinones which, in addition to being otherwise optionally substituted on both the pyrrole and 2-indolinone portions of the compound, are necessarily substituted on the pyrrole moiety with one or more hydrocarbon chains which themselves are substituted with at least one polar group. The formulations and the compounds themselves are useful for the treatment of protein kinase related disorders as discussed herein.

  本发明涉及吲哚酮的配方，这些化合物作为游离酸或游离碱是可离子化的。该配方适用于静脉或口服给药，其中配方包括可离子化的取代吲哚酮和其药用可接受载体。术语“可离子化的取代吲哚酮”包括吡咯取代的2-吲哚酮，除了在化合物的吡咯和2-吲哚酮部分上可选择地被取代外，必须在吡咯基上用一个或多个烃链取代，这些烃链本身被至少一个极性基团取代。如本文所述，这些配方和化合物本身对于治疗蛋白激酶相关疾病是有用的。
• Indolinone derivatives as protein kinase/phosphatase inhibitors
  申请人：——

  公开号：US20020052369A1

  公开（公告）日：2002-05-02

  The present invention relates to certain 2-indolinone compounds which modulate the activity of protein kinases (“PKs”) and phosphatases. The compounds of this invention are therefore useful in treating disorders related to abnormal PK activity. Pharmaceutical compositions comprising these compounds, methods of treating diseases utilizing pharmaceutical compositions comprising these compounds and methods of preparing them are also disclosed.

  本发明涉及调节蛋白激酶（“PKs”）和磷酸酶活性的某些2-吲哚酮化合物。因此，本发明的化合物在治疗与异常PK活性相关的疾病方面是有用的。还公开了包含这些化合物的药物组合物、利用包含这些化合物的药物组合物治疗疾病的方法以及制备它们的方法。
• Pyrrole substituted 2-indolinone protein kinase inhibitors
  申请人：Sugen, Inc.

  公开号：US06395734B1

  公开（公告）日：2002-05-28

  The present invention relates to novel pyrrole substituted 2-indolinone compounds and physiologically acceptable salts and prodrugs thereof which modulate the activity of protein kinases and therefore are expected to be useful in the prevention and treatment of protein kinase related cellular disorders such as cancer.

  本发明涉及新颖的吡咯替代的2-吲哚酮化合物及其生理上可接受的盐和前药，这些化合物调节蛋白激酶的活性，因此预计在预防和治疗蛋白激酶相关的细胞疾病，如癌症方面具有用处。
• 3-(Piperazinylbenzylidenyl)-2-indolinone compounds and derivatives as protein tyrosine kinase inhibitors
  申请人：SUGEN, Inc.

  公开号：US20030069421A1

  公开（公告）日：2003-04-10

  The present invention relates to novel 3-(piperazinyl-benylidenyl)-2-indolinone compounds and derivatives and physiologically acceptable salts thereof which are expected to modulate the activity of protein tyrosine kinases and therefore to be useful in the prevention and treatment of protein tyrosine kinase related cellular disorders such as cancer.

  本发明涉及新颖的3-(哌嗪基苄亚基)-2-吲哚酮化合物及其衍生物和生理上可接受的盐，预计这些化合物可以调节蛋白酪氨酸激酶的活性，因此在预防和治疗蛋白酪氨酸激酶相关的细胞疾病，如癌症方面具有用处。