methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate | 1052647-70-7

• 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 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
• CAS: 1052647-70-7
• 化学式: C₁₄H₁₇BCl₂O₄
• 分子量: 331.004
• InChiKey: YGILACHSZKSTEJ-UHFFFAOYSA-N

物化性质

• 沸点：
  410.9±45.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.08
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate 在 四(三苯基膦)钯 、 水 、 potassium carbonate 、 1-丙基磷酸酐 、 N,N-二异丙基乙胺 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 lithium hydroxide 作用下， 以 2-甲基四氢呋喃 、 1,4-二氧六环 、 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 42.17h， 生成 N-((1H-pyrazol-4-yl)methyl)-5-(2,4-dichloro-5-(pyridin-2-yl)benzamido)-1-phenyl-1H-pyrazole-3-carboxamide
  参考文献：
  名称：

  [EN] TROPOMYOSIN-RELATED KINASE INHIBITORS
  [FR] INHIBITEURS DE KINASES APPARENTÉES À LA TROPOMYOSINE

  摘要：

  本发明涉及式I化合物及其药用可接受的盐，其中取代基如本文所述，并且在医学上的应用，特别是作为TrkA拮抗剂。

  公开号：

  WO2015170218A1
• 作为产物：
  描述：

  2,4-二氯苯甲酸 在 (1,5-cyclooctadiene)(methoxy)iridium(I) dimer 、 硫酸 、 4,4'-二叔丁基-2,2'-二吡啶 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 生成 methyl 2,4-dichloro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate
  参考文献：
  名称：

  Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors

  摘要：

  Tropomyosin receptor kinases (TrkA, TrkB, TrkC) are activated by hormones of the neurotrophin family: nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT3), and neurotrophin 4 (NT4). Moreover, the NGF antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA kinase pathway in pain leading to significant interest in the development of small molecule inhibitors of TrkA. However, achieving TrkA subtype selectivity over TrkB and TrkC via a Type I and Type II inhibitor binding mode has proven challenging and Type III or Type IV allosteric inhibitors may present a more promising selectivity design approach. Furthermore, TrkA inhibitors with minimal brain availability are required to deliver an appropriate safety profile. Herein, we describe the discovery of a highly potent, subtype selective, peripherally restricted, efficacious, and well-tolerated series of allosteric TrkA inhibitors that culminated in the delivery of candidate quality compound 23.

  DOI：

  10.1021/acs.jmedchem.8b00280

文献信息

• Macrocyclic Compound
  申请人：Shimma Nobuo

  公开号：US20100056510A1

  公开（公告）日：2010-03-04

  The present invention provides a novel class of compounds that have the activity of inhibiting HSP90 enzyme and are useful as anti-cancer agents or such, and compounds that are useful as synthetic intermediates thereof. Specifically, the present invention provides compounds represented by the following formula (1), and pharmaceutically acceptable salts thereof: wherein X, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , L 1 , L 2 , and L 3 are as defined in the specification.

  本发明提供了一种新型化合物类，具有抑制HSP90酶活性的特性，可用作抗癌剂或其他用途，以及用作其合成中间体的化合物。具体而言，本发明提供了以下式（1）所表示的化合物及其药学上可接受的盐：其中，X、R1、R2、R3、R4、R5、R6、R7、L1、L2和L3如规范中所定义。
• Macrocyclic compound
  申请人：Shimma Nobuo

  公开号：US08362236B2

  公开（公告）日：2013-01-29

  The present invention provides a novel class of compounds that have the activity of inhibiting HSP90 enzyme and are useful as anti-cancer agents or such, and compounds that are useful as synthetic intermediates thereof. Specifically, the present invention provides compounds represented by the following formula (1), and pharmaceutically acceptable salts thereof: wherein X, R1, R2, R3, R4, R5, R6, R7, L1, L2, and L3 are as defined in the specification.

  本发明提供了一种新型化合物类别，具有抑制HSP90酶活性的作用，并可用作抗癌剂等，以及作为其合成中间体的化合物。具体而言，本发明提供以下式（1）所表示的化合物及其药学上可接受的盐：其中X，R1，R2，R3，R4，R5，R6，R7，L1，L2和L3如规范中所定义。
• TROPOMYOSIN-RELATED KINASE INHIBITORS
  申请人：PFIZER INC

  公开号：US20150322043A1

  公开（公告）日：2015-11-12

  The present invention relates to compounds of Formula I and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their use in medicine, in particular as TrkA antagonists.

  本发明涉及公式I化合物及其药学上可接受的盐，其中取代基如本文所述，并且它们在医学上的应用，特别是作为TrkA拮抗剂。
• Tropomyosin-related kinase inhibitors
  申请人：PFIZER INC

  公开号：US09328096B2

  公开（公告）日：2016-05-03

  The present invention relates to compounds of Formula I and their pharmaceutically acceptable salts, wherein the substituents are as described herein, and their use in medicine, in particular as TrkA antagonists.

  本发明涉及公式I的化合物及其药学上可接受的盐，其中取代基如本文所述，并且它们在医学上的用途，特别是作为TrkA拮抗剂。
• HSP90 INHIBITOR
  申请人：CHUGAI SEIYAKU KABUSHIKI KAISHA

  公开号：EP2036895B1

  公开（公告）日：2013-01-16