6-bromo-2-(phenoxymethyl)-1H-imidazo[4,5-b]pyridine | 284664-26-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 英文名称: 6-bromo-2-(phenoxymethyl)-1H-imidazo[4,5-b]pyridine
• CAS: 284664-26-2
• 化学式: C₁₃H₁₀BrN₃O
• mdl: MFCD00680090
• 分子量: 304.146
• InChiKey: GVSFRLHWAWMXNM-UHFFFAOYSA-N

物化性质

• 沸点：
  510.8±40.0 °C(Predicted)
• 密度：
  1.607±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.076
• 拓扑面积：
  50.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromo-2-(phenoxymethyl)-1H-imidazo[4,5-b]pyridine 在 二氯双[二叔丁基-(4-二甲基氨基苯基)膦]钯(II) 、 sodium carbonate 、 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 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 N-butyl-5-(2-(phenoxymethyl)-3H-imidazo[4,5-b]pyridin-6-yl)thiophene-3-carboxamide
  参考文献：
  名称：

  Identification of 2,6-Disubstituted 3H-Imidazo[4,5-b]pyridines as Therapeutic Agents for Dysferlinopathies through Phenotypic Screening on Patient-Derived Induced Pluripotent Stem Cells

  摘要：

  Dysferlinopathies, which are muscular diseases caused by mutations in the dysferlin gene, remain serious medical problems due to the lack of therapeutic agents. Herein, we report the design, synthesis, and structure activity relationships of a 2,6-disubstituted 3H-imidazo[4,5-b]pyridine series, which was identified from the phenotypic screening of chemicals that increase the level of dysferlin in myocytes differentiated from patient-derived induced pluripotent stem cells (iPSCs). Optimization studies with cell-based phenotypic assay led to the identification of a highly potent compound, 19, with dysferlin elevation effects at double-digit nanomolar concentrations. In addition, the molecular target of our chemical series was identified as tubulin, through a tubulin polymerization assay and a competitive binding assay using a photoaffinity labeling probe.

  DOI：

  10.1021/acs.jmedchem.9b01100
• 作为产物：
  描述：

  苯氧乙酸 、 2,3-二氨基-5-溴吡啶 在 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 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 以65%的产率得到6-bromo-2-(phenoxymethyl)-1H-imidazo[4,5-b]pyridine
  参考文献：
  名称：

  Identification of 2,6-Disubstituted 3H-Imidazo[4,5-b]pyridines as Therapeutic Agents for Dysferlinopathies through Phenotypic Screening on Patient-Derived Induced Pluripotent Stem Cells

  摘要：

  Dysferlinopathies, which are muscular diseases caused by mutations in the dysferlin gene, remain serious medical problems due to the lack of therapeutic agents. Herein, we report the design, synthesis, and structure activity relationships of a 2,6-disubstituted 3H-imidazo[4,5-b]pyridine series, which was identified from the phenotypic screening of chemicals that increase the level of dysferlin in myocytes differentiated from patient-derived induced pluripotent stem cells (iPSCs). Optimization studies with cell-based phenotypic assay led to the identification of a highly potent compound, 19, with dysferlin elevation effects at double-digit nanomolar concentrations. In addition, the molecular target of our chemical series was identified as tubulin, through a tubulin polymerization assay and a competitive binding assay using a photoaffinity labeling probe.

  DOI：

  10.1021/acs.jmedchem.9b01100

文献信息

• Bicyclic derivative, its production and use
  申请人：Oda Tsuneo

  公开号：US20050101647A1

  公开（公告）日：2005-05-12

  The present invention provides a heterocyclic compound having potent tyrosine kinase-inhibiting activity represented by formula: (wherein, R 1b is a C 6-10 aryl group which has substituent(s), and the like; T a is a single bond, a C 1-6 alkyl group, —CH 2 O—, and the like; X and Y are the same or different, and each is a nitrogen atom which may have substituent(s), and the like; the broken line is a single bond or a double bond; Z a is a nitrogen atom or CH; W is a single bond, an oxygen atom, and the like; Q is a C 6-10 aryl group which may have substituent(s) or an aromatic heterocyclic group which may have substituent(s)); or a salt thereof and a pharmaceutical composition comprising thereof.

  本发明提供了一种具有强效酪氨酸激酶抑制活性的杂环化合物，其化学式表示为：（其中，R1是具有取代基的C6-10芳基基团等；Ta是单键，C1-6烷基基团，—CH2O—等；X和Y相同或不同，每个都是氮原子，可以具有取代基等；断裂线是单键或双键；Z是氮原子或CH；W是单键，氧原子等；Q是具有取代基的C6-10芳基基团或具有取代基的芳香杂环基团）或其盐以及含有该化合物的药物组合物。
• BICYCLIC DERIVATIVE, PROCESS FOR PRODUCING THE SAME, AND USE
  申请人：Takeda Chemical Industries, Ltd.

  公开号：EP1460067A1

  公开（公告）日：2004-09-22

  The present invention provides a heterocyclic compound having potent tyrosine kinase-inhibiting activity represented by formula: (wherein, R1b is a C6-10 aryl group which has substituent(s), and the like; Ta is a single bond, a C1-6 alkyl group, -CH2O-, and the like; X and Y are the same or different, and each is a nitrogen atom which may have substituent(s), and the like; the broken line is a single bond or a double bond; Za is a nitrogen atom or CH; W is a single bond, an oxygen atom, and the like; Q is a C6-10 aryl group which may have substituent(s) or an aromatic heterocyclic group which may have substituent(s)); or a salt thereof and a pharmaceutical composition comprising thereof.

  本发明提供了一种具有强效酪氨酸激酶抑制活性的杂环化合物，由式表示： (其中，R1b是具有取代基等的C6-10芳基；Ta是单键、C1-6烷基、-CH2O-等；X和Y相同或不同，且各自是可具有取代基等的氮原子；断线是单键或双键；Za是氮原子或CH；W是单键、氧原子等；Q是可能具有取代基的C6-10芳基或可能具有取代基的芳香杂环基团；或其盐和包含其的药物组合物。
• US7622479B2
  申请人：——

  公开号：US7622479B2

  公开（公告）日：2009-11-24
• Identification of 2,6-Disubstituted 3<i>H</i>-Imidazo[4,5-<i>b</i>]pyridines as Therapeutic Agents for Dysferlinopathies through Phenotypic Screening on Patient-Derived Induced Pluripotent Stem Cells
  作者：Hiroyuki Takada、Akira Kaieda、Michiko Tawada、Tomoko Nagino、Katsunori Sasa、Tatsuo Oikawa、Akiko Oki、Tomoya Sameshima、Kazumasa Miyamoto、Makoto Miyamoto、Yuko Kokubu、Ryuichi Tozawa、Hidetoshi Sakurai、Bunnai Saito

  DOI：10.1021/acs.jmedchem.9b01100

  日期：2019.10.24

  Dysferlinopathies, which are muscular diseases caused by mutations in the dysferlin gene, remain serious medical problems due to the lack of therapeutic agents. Herein, we report the design, synthesis, and structure activity relationships of a 2,6-disubstituted 3H-imidazo[4,5-b]pyridine series, which was identified from the phenotypic screening of chemicals that increase the level of dysferlin in myocytes differentiated from patient-derived induced pluripotent stem cells (iPSCs). Optimization studies with cell-based phenotypic assay led to the identification of a highly potent compound, 19, with dysferlin elevation effects at double-digit nanomolar concentrations. In addition, the molecular target of our chemical series was identified as tubulin, through a tubulin polymerization assay and a competitive binding assay using a photoaffinity labeling probe.