3-(2-bromo-5-fluorophenyl)-1-(2-trimethylsilylethoxymethyl)pyrazole-4-carbaldehyde | 959996-47-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 3-(2-bromo-5-fluorophenyl)-1-(2-trimethylsilylethoxymethyl)pyrazole-4-carbaldehyde
• 英文别名: 3-(2-bromo-5-fluorophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carbaldehyde；3-(2-Bromo-5-fluorophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carbaldehyde
• CAS: 959996-47-5
• 化学式: C₁₆H₂₀BrFN₂O₂Si
• 分子量: 399.335
• InChiKey: ZADKKWNFEVMXDN-UHFFFAOYSA-N

物化性质

• 沸点：
  445.7±45.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.58
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-bromo-5-fluorophenyl)-1-(2-trimethylsilylethoxymethyl)pyrazole-4-carbaldehyde 在 titanium(IV) isopropylate 、 盐酸 、 4-二甲氨基吡啶 、 cesium acetate 、 copper(II) iodide 、 二甲基亚砜 、 三乙胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 甲醇 、 二氯甲烷 为溶剂， 反应 41.5h， 生成 4-Cyclopropyl-8-fluoro-5-[6-(trifluoromethyl)pyridin-3-yl]sulfonyl-1,4-dihydropyrazolo[4,3-c]quinoline
  参考文献：
  名称：

  Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch

  摘要：

  Herein, we describe our strategy to design metabolically stable gamma-secretase inhibitors which are selective for inhibition of A beta generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of A beta generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered A in the CSF of healthy human volunteers.

  DOI：

  10.1021/jm301741t
• 作为产物：
  描述：

  2-碘-4-氟溴苯 在 四(三苯基膦)钯 、 异丙基氯化镁 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 水 为溶剂， 反应 21.0h， 生成 3-(2-bromo-5-fluorophenyl)-1-(2-trimethylsilylethoxymethyl)pyrazole-4-carbaldehyde
  参考文献：
  名称：

  Discovery of (R)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1H-pyrazolo[4,3-c]quinoline (ELND006) and (R)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2H-pyrazolo[4,3-c]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch

  摘要：

  Herein, we describe our strategy to design metabolically stable gamma-secretase inhibitors which are selective for inhibition of A beta generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of A beta generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered A in the CSF of healthy human volunteers.

  DOI：

  10.1021/jm301741t

文献信息

• Fused, Tricyclic Sulfonamide Inhibitors of Gamma Secretase
  申请人：Konradi W. Andrei

  公开号：US20080021056A1

  公开（公告）日：2008-01-24

  The invention provides compounds of formula I: or pharmaceutically salts thereof where R 1 , R 2 , and the A, B, and C-rings are as defined herein. Compounds of formula I are useful in treating or preventing cognitive disorders, such as Alzheimer's disease. The invention also encompasses pharmaceutical compositions comprising compounds or salts of formula I, methods of preparing the desired compounds, and methods of treating cognitive disorders, such as Alzheimer's disease, using the compounds or salts of formula I.

  该发明提供了公式I的化合物： 或其药用盐，其中R 1 ，R 2 和A、B和C环如本文所定义。公式I的化合物在治疗或预防认知障碍，如阿尔茨海默病方面是有用的。该发明还涵盖了包括公式I的化合物或盐的药物组合物，制备所需化合物的方法，以及使用公式I的化合物或盐治疗认知障碍，如阿尔茨海默病的方法。
• Discovery of (<i>R</i>)-4-Cyclopropyl-7,8-difluoro-5-(4-(trifluoromethyl)phenylsulfonyl)-4,5-dihydro-1<i>H</i>-pyrazolo[4,3-<i>c</i>]quinoline (ELND006) and (<i>R</i>)-4-Cyclopropyl-8-fluoro-5-(6-(trifluoromethyl)pyridin-3-ylsulfonyl)-4,5-dihydro-2<i>H</i>-pyrazolo[4,3-<i>c</i>]quinoline (ELND007): Metabolically Stable γ-Secretase Inhibitors that Selectively Inhibit the Production of Amyloid-β over Notch
  作者：Gary Probst、Danielle L. Aubele、Simeon Bowers、Darren Dressen、Albert W. Garofalo、Roy K. Hom、Andrei W. Konradi、Jennifer L. Marugg、Matthew N. Mattson、Martin L. Neitzel、Chris M. Semko、Hing L. Sham、Jenifer Smith、Minghua Sun、Anh P. Truong、Xiaocong M. Ye、Ying-zi Xu、Michael S. Dappen、Jacek J. Jagodzinski、Pamela S. Keim、Brian Peterson、Lee H. Latimer、David Quincy、Jing Wu、Erich Goldbach、Daniel K. Ness、Kevin P. Quinn、John-Michael Sauer、Karina Wong、Hongbin Zhang、Wes Zmolek、Elizabeth F. Brigham、Dora Kholodenko、Kang Hu、Grace T. Kwong、Michael Lee、Anna Liao、Ruth N. Motter、Patricia Sacayon、Pamela Santiago、Christopher Willits、Frédérique Bard、Michael P. Bova、Susanna S. Hemphill、Lam Nguyen、Lany Ruslim、Kevin Tanaka、Pearl Tanaka、William Wallace、Ted A. Yednock、Guriqbal S. Basi

  DOI：10.1021/jm301741t

  日期：2013.7.11

  Herein, we describe our strategy to design metabolically stable gamma-secretase inhibitors which are selective for inhibition of A beta generation over Notch. We highlight our synthetic strategy to incorporate diversity and chirality. Compounds 30 (ELND006) and 34 (ELND007) both entered human clinical trials. The in vitro and in vivo characteristics for these two compounds are described. A comparison of inhibition of A beta generation in vivo between 30, 34, Semagacestat 41, Begacestat 42, and Avagacestat 43 in mice is made. 30 lowered A in the CSF of healthy human volunteers.