3-(2-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carbaldehyde | 1190853-67-8

• 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-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carbaldehyde
• CAS: 1190853-67-8
• 化学式: C₁₆H₂₁BrN₂O₂Si
• 分子量: 381.344
• InChiKey: GFZPEZVQMIXNEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  22.0
• 可旋转键数：
  7.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  44.12
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(2-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carbaldehyde 在 titanium(IV) isopropylate 、 盐酸 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 21.5h， 生成
  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：

  ethyl 3-iodo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazole-4-carboxylate 在 四(三苯基膦)钯 、 dimethyl sulfide borane 、 碳酸氢钠 、 potassium carbonate 、 戴斯-马丁氧化剂 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙二醇二甲醚 、 二氯甲烷 、 水 为溶剂， 反应 157.5h， 生成 3-(2-bromophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-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

• Design, synthesis, and structure–activity relationship of novel orally efficacious pyrazole/sulfonamide based dihydroquinoline γ-secretase inhibitors
  作者：Anh P. Truong、Danielle L. Aubele、Gary D. Probst、Martin L. Neitzel、Chris M. Semko、Simeon Bowers、Darren Dressen、Roy K. Hom、Andrei W. Konradi、Hing L. Sham、Albert W. Garofalo、Pamela S. Keim、Jing Wu、Michael S. Dappen、Karina Wong、Erich Goldbach、Kevin P. Quinn、John-Michael Sauer、Elizabeth F. Brigham、William Wallace、Lan Nguyen、Susanna S. Hemphill、Michael P. Bova、Guriqbal Basi

  DOI：10.1016/j.bmcl.2009.07.092

  日期：2009.9

  In this Letter, we report our strategy to design potent and metabolically stable gamma-secretase inhibitors that are efficacious in reducing the cortical A beta x-40 levels in FVB mice via a single PO dose. (C) 2009 Elsevier Ltd. All rights reserved.