4R-(4-benzyloxyphenyl)-3-(4-fluorophenyl)-5S-(1R-hydroxy-3-phenylpropyl)oxazolidin-2-one | 1011264-93-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4R-(4-benzyloxyphenyl)-3-(4-fluorophenyl)-5S-(1R-hydroxy-3-phenylpropyl)oxazolidin-2-one
• 英文别名: (4R,5S)-3-(4-fluorophenyl)-5-[(1R)-1-hydroxy-3-phenylpropyl]-4-(4-phenylmethoxyphenyl)-1,3-oxazolidin-2-one
• CAS: 1011264-93-9
• 化学式: C₃₁H₂₈FNO₄
• 分子量: 497.566
• InChiKey: IBIPEXMJUUVWSL-IDZRBWSNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4R-(4-benzyloxyphenyl)-3-(4-fluorophenyl)-5S-(1R-hydroxy-3-phenylpropyl)oxazolidin-2-one 在 palladium on activated charcoal 环己烯 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 以74%的产率得到3-(4-fluorophenyl)-4R-(4-hydroxyphenyl)-5S-(1R-hydroxy-3-phenylpropyl)oxazolidin-2-one
  参考文献：
  名称：

  WO2008/104875

  摘要：

  公开号：
• 作为产物：
  描述：

  4R-(4-benzyloxyphenyl)-3-(4-fluorophenyl)-5S-(3-phenylpropionyl)oxazolidin-2-one 在 potassium tert-butylate 、 氢气 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 25.0 ℃ 、344.75 kPa 条件下， 反应 6.0h， 以92%的产率得到4R-(4-benzyloxyphenyl)-3-(4-fluorophenyl)-5S-(1R-hydroxy-3-phenylpropyl)oxazolidin-2-one
  参考文献：
  名称：

  Substituted oxazolidinones as novel NPC1L1 ligands for the inhibition of cholesterol absorption

  摘要：

  Cholesterol absorption inhibition (CAI) represents an important treatment option for hypercholesterolemia. Herein, we report the design and evaluation of a series of substituted oxazolidinones as ligands for the Niemann Pick C1 Like 1 (NPC1L1) protein, a key mediator of cholesterol transport. Novel analogs were initially evaluated in a brush border membrane NPC1L1 binding assay; subsequently, promising compounds were evaluated in vivo for acute inhibition of cholesterol absorption. These studies identified analogs with low micromolar NPC1L1 binding affinity and acute in vivo efficacy of >50% absorption inhibition at 3 mg/kg. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.11.083

文献信息

• WO2008/104875
  申请人：——

  公开号：——

  公开（公告）日：——
• [EN] OXAZOLIDINONES AS CHOLESTEROL ABSORPTION INHIBITORS<br/>[FR] OXAZOLIDINONES COMME INHIBITEURS D'ABSORPTION DE CHOLESTÉROL
  申请人：PFIZER PROD INC

  公开号：WO2008104875A1

  公开（公告）日：2008-09-04

  [EN] Novel oxazolidinones and pharmaceutical compositions are described, as are methods of using such compounds and compositions to treat subjects, including humans, suffering from hyperlipidemia, hypercholeserolemia, and atherosclerosis.
  [FR] L'invention porte sur de nouvelles oxazolidinones et compositions pharmaceutiques, ainsi que sur des procédés d'utilisation de tels composés et compositions pour traiter des sujets, y compris les êtres humains, souffrant d'hyperlipidémie, d'hypercholestérolémie et d'athérosclérose.
• Substituted oxazolidinones as novel NPC1L1 ligands for the inhibition of cholesterol absorption
  作者：Jeffrey A. Pfefferkorn、Scott D. Larsen、Chad Van Huis、Roderick Sorenson、Tom Barton、Thomas Winters、Bruce Auerbach、Chenyan Wu、Thaddeus J. Wolfram、Hongliang Cai、Kathleen Welch、Nadia Esmaiel、JoAnn Davis、Richard Bousley、Karl Olsen、Sandra Bak Mueller、Thomas Mertz

  DOI：10.1016/j.bmcl.2007.11.083

  日期：2008.1

  Cholesterol absorption inhibition (CAI) represents an important treatment option for hypercholesterolemia. Herein, we report the design and evaluation of a series of substituted oxazolidinones as ligands for the Niemann Pick C1 Like 1 (NPC1L1) protein, a key mediator of cholesterol transport. Novel analogs were initially evaluated in a brush border membrane NPC1L1 binding assay; subsequently, promising compounds were evaluated in vivo for acute inhibition of cholesterol absorption. These studies identified analogs with low micromolar NPC1L1 binding affinity and acute in vivo efficacy of >50% absorption inhibition at 3 mg/kg. (c) 2007 Elsevier Ltd. All rights reserved.