(2RS)-2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-2-(3-chlorophenyl)ethanoic acid | 1207438-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (2RS)-2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-2-(3-chlorophenyl)ethanoic acid
• 英文别名: 2-(3-Chlorophenyl)-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid；2-(3-chlorophenyl)-2-[1-[(2-methylpropan-2-yl)oxycarbonyl]piperidin-4-yl]acetic acid
• CAS: 1207438-55-8
• 化学式: C₁₈H₂₄ClNO₄
• 分子量: 353.846
• InChiKey: PMKUHGVMTBNNAI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2RS)-2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-2-(3-chlorophenyl)ethanoic acid 在 硼烷四氢呋喃络合物 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 0.33h， 生成 tert-butyl 4-[(1RS)-1-(3-chlorophenyl)-2-methoxyethyl]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
• 作为产物：
  描述：

  间氯氰苄 在 sodium tetrahydroborate 、 水 、 氢溴酸 、 sodium methylate 、 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 27.5h， 生成 (2RS)-2-[1-(tert-butoxycarbonyl)piperidin-4-yl]-2-(3-chlorophenyl)ethanoic acid
  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

文献信息

• 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
  作者：Yuji Ishichi、Eiji Kimura、Eiji Honda、Masato Yoshikawa、Takashi Nakahata、Yasuko Terao、Atsuko Suzuki、Takayuki Kawai、Yuuichi Arakawa、Hiroyuki Ohta、Naoyuki Kanzaki、Hideyuki Nakagawa、Jun Terauchi

  DOI：10.1016/j.bmc.2013.05.025

  日期：2013.8

  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.