4-bromo-1-fluoro-2-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>benzene | 99725-14-1

• 物质功能分类: 化学试剂 - 有机试剂 - 硅烷
• 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: 4-bromo-1-fluoro-2-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>benzene
• 英文别名: 4-Bromo-2-[[[(1,1-dimethylethyl)dimethylsilyl]oxy]methyl]-1-fluorobenzene；(5-bromo-2-fluorophenyl)methoxy-tert-butyl-dimethylsilane
• CAS: 99725-14-1
• 化学式: C₁₃H₂₀BrFOSi
• 分子量: 319.289
• InChiKey: JBQLTVJRMDWMNA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.11
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-bromo-1-fluoro-2-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>benzene 在 正丁基锂 、 N,N-二甲基甲酰胺 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 1.42h， 以57%的产率得到3-(t-butyldimethylsilanyloxymethyl)-4-fluorobenzaldehyde
  参考文献：
  名称：

  INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE

  摘要：

  本文披露了抑制RIPK1的化合物、制药组合物以及治疗RIPK1介导的疾病（如神经退行性疾病、炎症性疾病和癌症）的方法。

  公开号：

  US20210094921A1
• 作为产物：
  描述：

  2-氟-5-溴苄溴 在 咪唑 、 sodium hydroxide 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 32.5h， 生成 4-bromo-1-fluoro-2-<<<(1,1-dimethylethyl)dimethylsilyl>oxy>methyl>benzene
  参考文献：
  名称：

  3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 3. 7-(3,5-Disubstituted-[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives

  摘要：

  The syntheses of a series of 7-(3,5-disubstituted [1,1'-bephenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported. Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl moiety is substituted by chloro or methyl groups at positions 3 and 5 and a fluoro group at position 4'. These substitutions, followed by resolution, provided compounds 100(+) and 110(+) with 2.8 times the intrinsic inhibitory activity of compactin. Compound 100(+) was shown to possess the same chirality in the lactone ring as compactin by single-crystal X-ray crystallography.

  DOI：

  10.1021/jm00152a002

文献信息

• Augmentation of Anticancer Drug Efficacy in Murine Hepatocellular Carcinoma Cells by a Peripherally Acting Competitive <i>N</i>-Methyl-<scp>d</scp>-aspartate (NMDA) Receptor Antagonist
  作者：Mikko Gynther、Ilaria Proietti Silvestri、Jacob C. Hansen、Kasper B. Hansen、Tarja Malm、Yevheniia Ishchenko、Younes Larsen、Liwei Han、Silke Kayser、Seppo Auriola、Aleksanteri Petsalo、Birgitte Nielsen、Darryl S. Pickering、Lennart Bunch

  DOI：10.1021/acs.jmedchem.7b01624

  日期：2017.12.14

  inevitably acquire such when treated with anticancer drugs. In this work, we describe the discovery of a peripherally restricted, potent, competitive NMDA receptor antagonist 1l by a structure–activity study of the broad-acting ionotropic glutamate receptor antagonist 1a. Subsequently, we demonstrate that 1l augments the cytotoxic action of sorafenib in murine hepatocellular carcinoma cells. The underlying

  最常见的实体瘤表现出内在的多药耐药性（MDR），或者在用抗癌药治疗时不可避免地会获得这种耐药性。在这项工作中，我们通过对广谱离子型谷氨酸受体拮抗剂1a的结构-活性研究，描述了对周围受限，有效的竞争性NMDA受体拮抗剂1l的发现。随后，我们证明1l增强索拉非尼在鼠肝细胞癌细胞中的细胞毒作用。已显示出潜在的生物学机制是对脂质信号传导途径的干扰，从而导致MDR转运蛋白表达降低，从而索拉非尼在癌细胞中的积累增加。NMDA受体抑制干扰脂质信号通路是一种新颖且有前途的策略，用于逆转癌细胞中转运蛋白介导的化学抗性。
• SMITH, ROBERT L.;STOKKER, GERALD E.
  作者：SMITH, ROBERT L.、STOKKER, GERALD E.

  DOI：——

  日期：——
• STOKKER, G. E.;ALBERTS, A. W.;ANDERSON, P. S.;CRAGOE, E. J. ,, JR.;DEANA,+, J. MED. CHEM., 1986, 29, N 2, 170-181
  作者：STOKKER, G. E.、ALBERTS, A. W.、ANDERSON, P. S.、CRAGOE, E. J. ,, JR.、DEANA,+

  DOI：——

  日期：——
• 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors. 3. 7-(3,5-Disubstituted-[1,1'-biphenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactone derivatives
  作者：G. E. Stokker、A. W. Alberts、P. S. Anderson、E. J. Cragoe、A. A. Deana、J. L. Gilfillan、J. Hirshfield、W. J. Holtz、W. F. Hoffman

  DOI：10.1021/jm00152a002

  日期：1986.2

  The syntheses of a series of 7-(3,5-disubstituted [1,1'-bephenyl]-2-yl)-3,5-dihydroxy-6-heptenoic acids and their lactones are reported. Intrinsic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitory activity is enhanced markedly when the biphenyl moiety is substituted by chloro or methyl groups at positions 3 and 5 and a fluoro group at position 4'. These substitutions, followed by resolution, provided compounds 100(+) and 110(+) with 2.8 times the intrinsic inhibitory activity of compactin. Compound 100(+) was shown to possess the same chirality in the lactone ring as compactin by single-crystal X-ray crystallography.
• INHIBITORS OF RECEPTOR INTERACTING PROTEIN KINASE I FOR THE TREATMENT OF DISEASE
  申请人：Board of Regents, The University of Texas System

  公开号：US20210094921A1

  公开（公告）日：2021-04-01

  Disclosed herein are compounds which inhibit RIPK1, pharmaceutical compositions, and methods of treatment of RIPK1-mediated diseases, such as neurodegenerative disorders, inflammatory disorders, and cancer.

  本文披露了抑制RIPK1的化合物、制药组合物以及治疗RIPK1介导的疾病（如神经退行性疾病、炎症性疾病和癌症）的方法。