4R-(4-benzyloxy-phenyl)-3-(4-fluorophenyl)-2-oxo-oxazolidine-5S-carboxylic acid (4-fluorobenzyl)methylamide | 1053173-94-6

• 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-benzyloxy-phenyl)-3-(4-fluorophenyl)-2-oxo-oxazolidine-5S-carboxylic acid (4-fluorobenzyl)methylamide
• 英文别名: (4R,5S)-3-(4-fluorophenyl)-N-[(4-fluorophenyl)methyl]-N-methyl-2-oxo-4-(4-phenylmethoxyphenyl)-1,3-oxazolidine-5-carboxamide
• CAS: 1053173-94-6
• 化学式: C₃₁H₂₆F₂N₂O₄
• 分子量: 528.555
• InChiKey: UUVDPPQNNIROOZ-WDYNHAJCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  39
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4R-(4-benzyloxy-phenyl)-3-(4-fluorophenyl)-2-oxo-oxazolidine-5S-carboxylic acid (4-fluorobenzyl)methylamide 在 palladium on activated charcoal 环己烯 作用下， 以 乙醇 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 3-(4-fluorophenyl)-4R-(4-hydroxyphenyl)-2-oxo-oxazolidine-5S-carboxylic acid (4-fluorobenzyl)methylamide
  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
• 作为产物：
  描述：

  4R-(4-benzyloxyphenyl)-3-(4-fluorophenyl)-2-oxo-oxazolidine-5S-carboxylic acid 、 N-甲基-4-氟苄胺 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 生成 4R-(4-benzyloxy-phenyl)-3-(4-fluorophenyl)-2-oxo-oxazolidine-5S-carboxylic acid (4-fluorobenzyl)methylamide
  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

• 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.