(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dimethyl-1,3-oxazolidin-2-one | 1312671-78-5

• 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: (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dimethyl-1,3-oxazolidin-2-one
• CAS: 1312671-78-5
• 化学式: C₁₃H₁₁F₆NO₂
• 分子量: 327.226
• InChiKey: QGKVOLFRANBJKE-KGFZYKRKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2'-(溴甲基)-4-氟-5-异丙基-2-甲氧基-4'-(三氟甲基)-1,1'-二苯 、 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dimethyl-1,3-oxazolidin-2-one 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.25h， 以65%的产率得到(+)-(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-{[4'-fluoro-2'-methoxy-5'-(propan-2-yl)-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4,5-dimethyl-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Biphenyl-Substituted Oxazolidinones as Cholesteryl Ester Transfer Protein Inhibitors: Modifications of the Oxazolidinone Ring Leading to the Discovery of Anacetrapib

  摘要：

  The development of the structure-activity studies leading to the discovery of anacetrapib is described. These studies focused on varying the substitution of the oxazolidinone ring of the 5-aryloxazolidinone system. Specifically, it was found that substitution of the 4-position with a methyl group with the cis-stereochemistry relative to the 5-aryl group afforded compounds with increased cholesteryl ester transfer protein (CETP) inhibition potency and a robust in vivo effect on increasing HDL-C levels in transgenic mice expressing cynomolgus monkey CETP.

  DOI：

  10.1021/jm200484c
• 作为产物：
  描述：

  benzyl (1S)-2-[3,5-bis(trifluoromethyl)phenyl]-1-methyl-2-oxoethylcarbamate 在 水 、 potassium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 为溶剂， 反应 2.0h， 生成 (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4,5-dimethyl-1,3-oxazolidin-2-one
  参考文献：
  名称：

  Biphenyl-Substituted Oxazolidinones as Cholesteryl Ester Transfer Protein Inhibitors: Modifications of the Oxazolidinone Ring Leading to the Discovery of Anacetrapib

  摘要：

  The development of the structure-activity studies leading to the discovery of anacetrapib is described. These studies focused on varying the substitution of the oxazolidinone ring of the 5-aryloxazolidinone system. Specifically, it was found that substitution of the 4-position with a methyl group with the cis-stereochemistry relative to the 5-aryl group afforded compounds with increased cholesteryl ester transfer protein (CETP) inhibition potency and a robust in vivo effect on increasing HDL-C levels in transgenic mice expressing cynomolgus monkey CETP.

  DOI：

  10.1021/jm200484c

文献信息

• Biphenyl-Substituted Oxazolidinones as Cholesteryl Ester Transfer Protein Inhibitors: Modifications of the Oxazolidinone Ring Leading to the Discovery of Anacetrapib
  作者：Cameron J. Smith、Amjad Ali、Milton L. Hammond、Hong Li、Zhijian Lu、Joann Napolitano、Gayle E. Taylor、Christopher F. Thompson、Matt S. Anderson、Ying Chen、Suzanne S. Eveland、Qiu Guo、Sheryl A. Hyland、Denise P. Milot、Carl P. Sparrow、Samuel D. Wright、Anne-Marie Cumiskey、Melanie Latham、Laurence B. Peterson、Ray Rosa、James V. Pivnichny、Xinchun Tong、Suoyu S. Xu、Peter J. Sinclair

  DOI：10.1021/jm200484c

  日期：2011.7.14

  The development of the structure-activity studies leading to the discovery of anacetrapib is described. These studies focused on varying the substitution of the oxazolidinone ring of the 5-aryloxazolidinone system. Specifically, it was found that substitution of the 4-position with a methyl group with the cis-stereochemistry relative to the 5-aryl group afforded compounds with increased cholesteryl ester transfer protein (CETP) inhibition potency and a robust in vivo effect on increasing HDL-C levels in transgenic mice expressing cynomolgus monkey CETP.