5-methoxy-1-methyl-1-(trifluoromethyl)indane | 959842-20-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 5-methoxy-1-methyl-1-(trifluoromethyl)indane
• 英文别名: 6-Methoxy-3-methyl-3-(trifluoromethyl)-1,2-dihydroindene；6-methoxy-3-methyl-3-(trifluoromethyl)-1,2-dihydroindene
• CAS: 959842-20-7
• 化学式: C₁₂H₁₃F₃O
• 分子量: 230.23
• InChiKey: IVUBWTJUVDUCLV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5-methoxy-1-methyl-1-(trifluoromethyl)indane 、 1,1-二氯甲醚 在 四氯化钛 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以85%的产率得到5-methoxy-1-methyl-1-(trifluoromethyl)indane-6-carboxaldehyde
  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
• 作为产物：
  描述：

  、 Dimethylzinc 以 正己烷 、 二氯甲烷 为溶剂， 以847 mg的产率得到5-methoxy-1-methyl-1-(trifluoromethyl)indane
  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

文献信息

• Synthesis of aromatic compounds containing a 1,1-dialkyl-2-trifluoromethyl group, a bioisostere of the tert-alkyl moiety
  作者：Hirotaka Tanaka、Yuji Shishido

  DOI：10.1016/j.bmcl.2007.09.053

  日期：2007.11

  1,1-Dialkyl-2-perfluoroalkyl compounds, which are potential metabolically stable bioisosteres of the tert-alkyl moiety, have been synthesized from the corresponding tertiary alcohols using titanium (IV) chloride-dimethylzinc or trimethylaluminium as the source of the methyl group. The synthetic methods proved to be versatile for synthesizing 1,1-dimethyl-2,2,2-trifluoroethyl compounds and analogs, including compounds containing aromatic and heterocyclic rings. (C) 2007 Elsevier Ltd. All rights reserved.