tert-butyl 4-[(1RS)-2-hydroxy-1-(naphthalen-2-yl)ethyl]piperidine-1-carboxylate | 1447417-92-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: tert-butyl 4-[(1RS)-2-hydroxy-1-(naphthalen-2-yl)ethyl]piperidine-1-carboxylate
• CAS: 1447417-92-6
• 化学式: C₂₂H₂₉NO₃
• 分子量: 355.477
• InChiKey: VYEGECHAEGADIJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.56
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  49.77
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-[(1RS)-2-hydroxy-1-(naphthalen-2-yl)ethyl]piperidine-1-carboxylate 在 盐酸 、 乙醇 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.58h， 生成 4-[(1RS)-2-methoxy-1-(naphthalen-2-yl)ethyl]piperidine monohydrochloride
  参考文献：
  名称：

  Novel triple reuptake inhibitors with low risk of CAD associated liabilities: Design, synthesis and biological activities of 4-[(1S)-1-(3,4-dichlorophenyl)-2-methoxyethyl]piperidine and related compounds

  摘要：

  A novel triple reuptake inhibitor with low potential of liabilities associated with cationic amphiphilic drug (CAD) was identified following an analysis of existing drugs. Low molecular weight (MW < ca. 300), low aromatic ring count (number = 1) and reduced lipophilicity (ClogP < 3.5) were hypothesized to be key factors to avoid the CAD associated liabilities (CYP2D6 inhibition, hERG inhibition and phospholipidosis). Based on the hypothesis, a series of piperidine compounds was designed with consideration of the common characteristic features of CNS drugs. Optimization of the side chain by adjusting overall lipophilicity suggested that incorporation of a methoxymethyl group could provide compounds with a balance of both potent reuptake inhibition and low liability potential. Compound (S)-3a showed a potent antidepressant-like effect in the mice tail suspension test (MED = 10 mg/kg, p.o.), proportional monoamine transporter occupancies and enhancement of monoamine concentrations in mouse prefrontal cortex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.025
• 作为产物：
  描述：

  2-萘乙腈 在 sodium tetrahydroborate 、 硼烷四氢呋喃络合物 、 水 、 氢溴酸 、 sodium methylate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 27.5h， 生成 tert-butyl 4-[(1RS)-2-hydroxy-1-(naphthalen-2-yl)ethyl]piperidine-1-carboxylate
  参考文献：
  名称：

  Novel triple reuptake inhibitors with low risk of CAD associated liabilities: Design, synthesis and biological activities of 4-[(1S)-1-(3,4-dichlorophenyl)-2-methoxyethyl]piperidine and related compounds

  摘要：

  A novel triple reuptake inhibitor with low potential of liabilities associated with cationic amphiphilic drug (CAD) was identified following an analysis of existing drugs. Low molecular weight (MW < ca. 300), low aromatic ring count (number = 1) and reduced lipophilicity (ClogP < 3.5) were hypothesized to be key factors to avoid the CAD associated liabilities (CYP2D6 inhibition, hERG inhibition and phospholipidosis). Based on the hypothesis, a series of piperidine compounds was designed with consideration of the common characteristic features of CNS drugs. Optimization of the side chain by adjusting overall lipophilicity suggested that incorporation of a methoxymethyl group could provide compounds with a balance of both potent reuptake inhibition and low liability potential. Compound (S)-3a showed a potent antidepressant-like effect in the mice tail suspension test (MED = 10 mg/kg, p.o.), proportional monoamine transporter occupancies and enhancement of monoamine concentrations in mouse prefrontal cortex. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.05.025