2'-(4-chloro-2-fluorophenyl)-7'-methoxy-5H-spiro[oxazole-4,9'-xanthen]-2-amine 2,2,2-trifluoroacetate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 2'-(4-chloro-2-fluorophenyl)-7'-methoxy-5H-spiro[oxazole-4,9'-xanthen]-2-amine 2,2,2-trifluoroacetate
• 英文别名: 2'-(4-chloro-2-fluorophenyl)-7'-methoxyspiro[5H-1,3-oxazole-4,9'-xanthene]-2-amine;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₂H₁₆ClFN₂O₃
• 分子量: 524.856
• InChiKey: AOHVUSQMKNZEQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.48
• 重原子数：
  36
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  2′-bromo-7′-methoxyspiro[1,3-oxazole-4,9′-xanthen]-2-amine 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 18.0h， 生成 2'-(4-chloro-2-fluorophenyl)-7'-methoxy-5H-spiro[oxazole-4,9'-xanthen]-2-amine 2,2,2-trifluoroacetate
  参考文献：
  名称：

  Structure- and Property-Based Design of Aminooxazoline Xanthenes as Selective, Orally Efficacious, and CNS Penetrable BACE Inhibitors for the Treatment of Alzheimer’s Disease

  摘要：

  A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human beta-secretase inhibitors. These compounds exhibited good isolated enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound ha resulted in a significant reduction of CNS A beta 40 in naive rats.

  DOI：

  10.1021/jm300598e

文献信息

• Structure- and Property-Based Design of Aminooxazoline Xanthenes as Selective, Orally Efficacious, and CNS Penetrable BACE Inhibitors for the Treatment of Alzheimer’s Disease
  作者：Hongbing Huang、Daniel S. La、Alan C. Cheng、Douglas A. Whittington、Vinod F. Patel、Kui Chen、Thomas A. Dineen、Oleg Epstein、Russell Graceffa、Dean Hickman、Y.-H. Kiang、Steven Louie、Yi Luo、Robert C. Wahl、Paul H. Wen、Stephen Wood、Robert T. Fremeau

  DOI：10.1021/jm300598e

  日期：2012.11.8

  A structure- and property-based drug design approach was employed to identify aminooxazoline xanthenes as potent and selective human beta-secretase inhibitors. These compounds exhibited good isolated enzyme, cell potency, and selectivity against the structurally related aspartyl protease cathepsin D. Our efforts resulted in the identification of a potent, orally bioavailable CNS penetrant compound that exhibited in vivo efficacy. A single oral dose of compound ha resulted in a significant reduction of CNS A beta 40 in naive rats.