4-[[3-Chloro-4-(diethoxyphosphorylmethyl)phenoxy]methyl]-5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole | 1268246-09-8

• 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-[[3-Chloro-4-(diethoxyphosphorylmethyl)phenoxy]methyl]-5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole
• 英文别名: 4-[[3-chloro-4-(diethoxyphosphorylmethyl)phenoxy]methyl]-5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole
• CAS: 1268246-09-8
• 化学式: C₂₄H₂₅Cl₃NO₅P
• 分子量: 544.799
• InChiKey: HWCXUDVGBWITJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  34
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  70.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-[[3-Chloro-4-(diethoxyphosphorylmethyl)phenoxy]methyl]-5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole 在 palladium diacetate sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 生成 5-[2-[2-Chloro-4-[[5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazol-4-yl]methoxy]phenyl]cyclopropyl]-3-(methoxymethoxy)-1,2-benzoxazole
  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：

  4-(氯甲基)-5-环丙基-3-(2,6-二氯苯基)-1,2-恶唑 在 sodium tetrahydroborate 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.5h， 生成 4-[[3-Chloro-4-(diethoxyphosphorylmethyl)phenoxy]methyl]-5-cyclopropyl-3-(2,6-dichlorophenyl)-1,2-oxazole
  参考文献：
  名称：

  Novel substituted isoxazole FXR agonists with cyclopropyl, hydroxycyclobutyl and hydroxyazetidinyl linkers: Understanding and improving key determinants of pharmacological properties

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2016.05.070

文献信息

• 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
• 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.
• [EN] NOVEL FXR (NR1H4 ) BINDING AND ACTIVITY MODULATING COMPOUNDS<br/>[FR] NOUVEAUX COMPOSÉS SE LIANT AU FXR (NR1 H4) ET MODULANT SON ACTIVITÉ
  申请人：PHENEX PHARMACEUTICALS AG

  公开号：WO2011020615A1

  公开（公告）日：2011-02-24

  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.

  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。