(1S)-6-acetoxy-1-methyl-1-trifluoromethylisochroman | 309967-07-5

• 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: (1S)-6-acetoxy-1-methyl-1-trifluoromethylisochroman
• CAS: 309967-07-5
• 化学式: C₁₃H₁₃F₃O₃
• 分子量: 274.24
• InChiKey: AEKVTYPHESXBID-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.96
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  35.53
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  6-acetoxy-1-methyl-1-trifluoromethylisochroman 在 Pseudomonas sp. lipase PS 作用下， 以 正己烷 、 仲丁醇 为溶剂， 生成 (1R)-6-acetoxy-1-methyl-1-trifluoromethylisochroman 、 (1S)-6-hydroxy-1-methyl-1-trifluoromethylisochroman 、 (1S)-6-acetoxy-1-methyl-1-trifluoromethylisochroman
  参考文献：
  名称：

  Discovery and stereoselective synthesis of the novel isochroman neurokinin-1 receptor antagonist ‘CJ-17,493’

  摘要：

  A novel central nervous system (CNS) selective neurokinin-1 (NK1) receptor antagonist, (2S, 3S)-3-[(1R)-6-methoxy- 1-methyl-1-trifluoromethylisochroman-7-yl]-methylamino-2-phenylpiperidine 'CJ-17,493'( compound (+)-1), was synthesized stereoselectively using a kinetic resolution by lipase-PS as a key step. Compound (+)-1 displayed high and selective affinity (K-i = 0.2 nM) for the human NK1 receptor in IM-9 cells, potent activity in the [Sar(9), Met(O-2)(11)] SP-induced gerbil tapping model (ED50 = 0.04 mg/kg, sc) and in the ferret cisplatin (10 mg/kg, ip)-induced anti-emetic activity model (vomiting: ED90 = 0.07 mg/kg, sc), all levels of activity comparable with those of CP-122,721. In addition, compound (+)-1 exhibited linear pharmacokinetics rather than the super dose-proportionality of CP-122,721 and this result provides a potential solution for the clinical issue observed with CP-122,721. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.06.047