2-[5-（3-氯苯基）-2-呋喃基]-4,5-双（4-甲氧基苯基）-1H-咪唑 | 937807-66-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 2-[5-（3-氯苯基）-2-呋喃基]-4,5-双（4-甲氧基苯基）-1H-咪唑
• 英文名称: neurodazine
• 英文别名: 2-[5-(3-chlorophenyl)furan-2-yl]-4,5-bis(4-methoxyphenyl)-1H-imidazole
• CAS: 937807-66-4
• 化学式: C₂₇H₂₁ClN₂O₃
• 分子量: 456.928
• InChiKey: FEEOFPAEDSMOTO-UHFFFAOYSA-N

物化性质

• 沸点：
  661.4±55.0 °C(Predicted)
• 密度：
  1.252±0.06 g/cm3(Predicted)
• 溶解度：
  二甲基亚砜：>20mg/mL

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  二甲胺 、 2-[5-（3-氯苯基）-2-呋喃基]-4,5-双（4-甲氧基苯基）-1H-咪唑 在 potassium hydroxide 、 potassium hexacyanoferrate(III) 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以7 %的产率得到
  参考文献：
  名称：

  笼养生物活性三芳基咪唑：一种制造可见光激活药物的方法

  摘要：

  咪唑是各种小分子抑制剂的重要结构成分，这些小分子抑制剂旨在抗癌治疗中针对不同激酶。然而，此类抑制剂的有效性常常受到非特异性作用和耐药性发展的阻碍。光药理学通过以时空精度对药物活性进行外部控制，提供了一种引人注目的解决方案。在此，我们介绍了一种用于捕获基于三芳基咪唑的生物活性药物分子的新策略。该方法涉及在咪唑环的碳原子上引入二烷基氨基作为光可去除基团，其本质上将核心结构从平面咪唑调节为四面体2H-咪唑，使得笼状化合物在可见光照射下选择性地释放。我们将这种创新的笼蔽技术应用于SB431542 ，这是一种基于三芳基咪唑的小分子抑制剂，针对关键的 TGF-β 信号通路，该信号通路的失调与包括癌症在内的多种人类疾病有关。我们的结果证明了光激活对体外人乳腺癌细胞迁移的选择性抑制，突显了我们的方法将基于三芳基咪唑的药物分子转化为可见光激活药物的潜力，从而促进其药理活性的时空调节。

  DOI：

  10.1021/jacs.4c04468
• 作为产物：
  描述：

  4,5-dibromo-2-(2-furyl)-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-imidazole 在 N-溴代丁二酰亚胺(NBS) 、 四(三苯基膦)钯 、 四丁基氟化铵 、 potassium carbonate 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 12.0h， 生成 2-[5-（3-氯苯基）-2-呋喃基]-4,5-双（4-甲氧基苯基）-1H-咪唑
  参考文献：
  名称：

  Selective Sequential Cross-Coupling Reactions on Imidazole towards Neurodazine and Analogues

  摘要：

  Polysubstituted imidazoles represent a common structural motif in bioactive molecules. A modular and flexible strategy towards 2,4,5-triarylated imidazoles is reported applying a Suzuki-Miyaura cross-coupling protocol. Employing 1-protected 2,4,5-tribromoimidazole as starting material, both stepwise and one-pot protocols towards the title compounds are disclosed. The utility of the approach was demonstrated by synthesizing neurodazine, a biologically active molecule affecting neuronal cell differentiation.

  DOI：

  10.1055/s-0032-1316906

文献信息

• Compounds inducing differentiation of myoblasts or muscle fibers into neuron cells, pharmaceutical composition including said compounds, a method for inducing neuron differentiation and a screening method for identifying additional compounds useful for inducing neuron differentiation
  申请人：Shin In-Jae

  公开号：US20070123576A1

  公开（公告）日：2007-05-31

  The present invention relates to compounds inducing differentiation of myoblasts or muscle fibers into neuron cells, pharmaceutical composition including said compounds, a method for inducing neuron differentiation and a screening method for identifying additional compounds useful for inducing neuron differentiation. More specifically, it relates to compounds that induce neuron differentiation from myoblasts or muscle fibers, all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrugs thereof, the method of inducing differentiation of myoblasts or muscle fibers into neuron cells by treating myoblasts and muscle fibers with a compound of the present invention, whereby the myoblasts and muscle fibers differentiate into neuron cells, and the screening method for identifying additional compounds useful for inducing neuron differentiation, wherein myoblasts and muscle fibers are incubated with a compound of the present invention and detected.

  本发明涉及诱导肌母细胞或肌纤维分化为神经元细胞的化合物、包括该化合物的制药组合物、诱导神经元分化的方法以及用于识别其他有用的诱导神经元分化的化合物的筛选方法。更具体地说，涉及诱导神经元分化的化合物，包括肌母细胞或肌纤维的所有药学上可接受的异构体、盐、水合物、溶剂化合物和前药，通过用本发明的化合物处理肌母细胞和肌纤维来诱导肌母细胞和肌纤维分化为神经元细胞的方法，并且用于识别其他有用的诱导神经元分化的化合物的筛选方法，其中肌母细胞和肌纤维与本发明的化合物孵育并检测。
• 4,5-BIS(4-METHOXYPHENYL)IMIDAZOLE COMPOUND INDUCING DIFFERENTIATION OF MYOBLASTS OR MUSCLE FIBERS INTO NEURON CELLS, A PHARMACEUTICAL COMPOSITION INCLUDING SAID COMPOUND, A METHOD OF INDUCING NEURON CELLS DIFFERENTIATION AND A SCREENING METHOD FOR IDENTIFYING ADDITIONAL COMPOUND USEFUL FOR INDUCING NEURON CELLS DIFFERENTIATION
  申请人：Shin In-Jae

  公开号：US20100184097A1

  公开（公告）日：2010-07-22

  The present invention relates to 4,5-bis(4-methoxyphenyl)imidazole compound inducing differentiation of myoblasts or muscle fibers into neuron cells, a pharmaceutical composition including said compound, a method of inducing neuron cells differentiation and a screening method for identifying additional compound useful for inducing neuron cells differentiation. More specifically, it relates to 2-2-[5-(3-chlorophenyl)]furanyl}-4,5-bis(4-methoxyphenyl)imidazole that induces differentiation of myoblasts or muscle fibers into neuron cells, all pharmaceutically acceptable isomers, salts, hydrates, solvates and prodrug thereof, and a pharmaceutical composition including said compound, a method of inducing neuron cells differentiation and a screening method for identifying additional compound useful for inducing neuron cells differentiation.

  本发明涉及一种4,5-双（4-甲氧基苯基）咪唑化合物，该化合物能够诱导肌母细胞或肌纤维分化为神经元细胞，以及包括该化合物的制药组合物、诱导神经元细胞分化的方法和用于鉴定其他用于诱导神经元细胞分化的有用化合物的筛选方法。更具体地，本发明涉及2-2-[5-(3-氯苯基) ]呋喃基}-4,5-双（4-甲氧基苯基）咪唑化合物，该化合物能够诱导肌母细胞或肌纤维分化为神经元细胞，包括其所有药学上可接受的异构体、盐、水合物、溶剂化合物和前药，以及包括该化合物的制药组合物、诱导神经元细胞分化的方法和用于鉴定其他用于诱导神经元细胞分化的有用化合物的筛选方法。
• Triorganoindium Reagents in Selective Palladium-Catalyzed Cross-Coupling with Iodoimidazoles: Synthesis of Neurodazine
  作者：Cristina Pérez-Caaveiro、José Pérez Sestelo、M. Montserrat Martínez、Luis A. Sarandeses

  DOI：10.1021/jo501664p

  日期：2014.10.17

  Triorganoindium reagents (R3In, R = aryl, heteroaryl, alkynyl) react selectively under palladium catalysis with N-benzyl-2,4,5-triiodoimidazole to afford the C-2 monocoupling products. The reaction proceeds efficiently for a variety of aryl- and heteroarylindium reagents with the transfer of all three organic groups attached to the metal. The coupling products can be used in a subsequent two-fold cross-coupling to give trisubstituted imidazoles in good yields. This approach was employed to synthesize neurodazine and analogues in good yields.
• WO2007/61153
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthetic Small Molecules that Induce Neurogenesis in Skeletal Muscle
  作者：Darren R. Williams、Myung-Ryul Lee、Young-Ah Song、Sung-Kyun Ko、Gun-Hee Kim、Injae Shin

  DOI：10.1021/ja072817z

  日期：2007.8.1

  Neurons are not regenerated effectively, and their injury causes neurodegenerative diseases. These diseases may be treated by the transplantation of neural stem cells. However, ethical and technical issues restrict cell therapies using neural stem cells. A more convenient and attractive approach is the use of small molecules with the capacity to induce neurogenesis from easily available cells or tissues. Such small molecules have the potential to allow tight controls over the timing and speed of cell differentiation. Herein, we describe the discovery of the first such molecule, neurodazine, identified by screening an imidazole library with C2C12 myoblasts. Further analyses show that neurodazine promotes the expression of neuron-specific markers in treated C2C12 cells. In addition, the use of neurodazines in conjunction with a microtubule-destabilizing agent allows neurogenic conversion of both differentiated immature myotubes and mature skeletal muscle.