2-Chlor-4-methoxybenzyldiaethylphosphonat | 67205-77-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-Chlor-4-methoxybenzyldiaethylphosphonat
• 英文别名: 2-Chloro-1-(diethoxyphosphorylmethyl)-4-methoxybenzene
• CAS: 67205-77-0
• 化学式: C₁₂H₁₈ClO₄P
• 分子量: 292.699
• InChiKey: QOSBLBOILHXHTM-UHFFFAOYSA-N

物化性质

• 沸点：
  140-144 °C(Press: 0.3 Torr)
• 密度：
  1.196±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-Chlor-4-methoxybenzyldiaethylphosphonat 在 palladium diacetate lithium hydroxide monohydrate 、 水 、 三溴化硼 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.5h， 生成 5-(2-(2-chloro-4-((5-cyclopropyl-3-(2,6-dichlorophenyl)isoxazol-4-yl)methoxy)phenyl)cyclopropyl)nicotinic acid
  参考文献：
  名称：

  [EN] NOVEL FXR (NR1H4 ) BINDING AND ACTIVITY MODULATING COMPOUNDS
  [FR] NOUVEAUX COMPOSÉS SE LIANT AU FXR (NR1 H4) ET MODULANT SON ACTIVITÉ

  摘要：

  本发明涉及结合NR1 H4受体（FXR）并作为NR1 H4受体（FXR）激动剂的化合物。该发明还涉及利用这些化合物制备药物用于通过这些化合物结合所述核受体治疗疾病和/或症状，并涉及这些化合物的合成过程。

  公开号：

  WO2011020615A1
• 作为产物：
  描述：

  2-氯-4-羟基苯甲醛 在 sodium tetrahydroborate 、 三溴化磷 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 0.83h， 生成 2-Chlor-4-methoxybenzyldiaethylphosphonat
  参考文献：
  名称：

  重氮转移反应合成 α-芳基重氮膦酸盐

  摘要：

  提出了通过重氮转移反应制备α-芳基-α-重氮膦酸盐的简单合成方法。在叔丁醇钾 (KO t Bu)的存在下，膦酸苄酯与叠氮化甲苯磺酰 (TsN 3 ) 反应得到重氮膦酸酯，产率高达 79%。建议的方法是通用的。该反应使用容易获得的起始材料，耐受各种官能团，可用于数克规模的合成。

  DOI：

  10.1021/acs.joc.1c02673

文献信息

• Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties
  作者：Olaf Kinzel、Christoph Steeneck、Thomas Schlüter、Andreas Schulz、Christian Gege、Ulrike Hahn、Eva Hambruch、Martin Hornberger、Adriana Spalwisz、Katharina Frick、Sanja Perović-Ottstadt、Ulrich Deuschle、Michael Burnet、Claus Kremoser

  DOI：10.1016/j.bmcl.2016.05.070

  日期：2016.8

  Several isoxazole-containing series of FXR agonists have been published over the last 15 years, subsequent to the prototypical amphiphilic 'hammerhead'-type structure that was originally laid out by GW4064, the first potent synthetic FXR agonist. A set of novel compounds where the hammerhead is connected to the terminal carboxylic acid-bearing aryl or heteroaryl moiety by either a cyclopropyl, a hydroxycyclobutyl or a hydroxyazetidinyl linker was synthesized in order to improve upon the ADME properties of such isoxazoles. The resulting compounds all demonstrated high potencies at the target receptor FXR but with considerable differences in their physicochemical and in vivo profiles. The structure-activity relationships for key chemical features that have a major impact on the in vivo pharmacology of this series are discussed. (C) 2016 Elsevier Ltd. All rights reserved.
• Antiviral activity of some .beta.-diketones. 4. Benzyl diketones. In vitro activity against both RNA and DNA viruses
  作者：G. D. Diana、Philip M. Carabateas、Robert E. Johnson、Gordon L. Williams、Francis Pancic、Joseph C. Collins

  DOI：10.1021/jm00207a010

  日期：1978.9

  The synthesis and in vitro antiviral evaluation of a series of substituted benzyl beta-diketones are described. The introduction of a styryl group onto the phenyl ring enhanced activity against herpesvirus type 2. The 4-methoxystyryl homologue 8 was evaluated extensively in vitro and was found to be effective against both RNA and DNA viruses. Compound 8 was evaluated in the mouse vagina against herpes simplex type 1 and produced a significant increase in survival rate as well as in survival time.
• DIANA G. D.; CARABATEAS P. M.; JOHNSON R. E.; WILLIAMS G. L.; PANCIC F.; +, J. MED. CHEM., 1978, 21, NO 9, 889-894
  作者：DIANA G. D.、 CARABATEAS P. M.、 JOHNSON R. E.、 WILLIAMS G. L.、 PANCIC F.、 +

  DOI：——

  日期：——
• NOVEL FXR (NR1H4) BINDING AND ACTIVITY MODULATING COMPOUNDS
  申请人：Kremoser Claus

  公开号：US20120232116A1

  公开（公告）日：2012-09-13

  The present invention relates to compounds which bind to the NR1 H4 receptor (FXR) and act as agonists of the NR1 H4 receptor (FXR). The invention further relates to the use of the compounds for the preparation of a medicament for the treatment of diseases and/or conditions through binding of said nuclear receptor by said compounds, and to a process for the synthesis of said compounds.
• US8952042B2
  申请人：——

  公开号：US8952042B2

  公开（公告）日：2015-02-10