4-[(1RS)-1-(3,4-dichlorophenyl)-2-(methylsulfonyl)ethyl]piperidine monohydrochloride | 1207436-40-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-[(1RS)-1-(3,4-dichlorophenyl)-2-(methylsulfonyl)ethyl]piperidine monohydrochloride
• 英文别名: 4-[1-(3,4-Dichlorophenyl)-2-methylsulfonylethyl]piperidine;hydrochloride；4-[1-(3,4-dichlorophenyl)-2-methylsulfonylethyl]piperidine;hydrochloride
• CAS: 1207436-40-5
• 化学式: C₁₄H₁₉Cl₂NO₂S*ClH
• 分子量: 372.743
• InChiKey: RPURJJSUIZKBOK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.54
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  54.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  tert-butyl 4-[(1RS)-1-(3,4-dichlorophenyl)-2-hydroxyethyl]piperidine-1-carboxylate 在 盐酸 、 乙醇 、 水 、 sodium hydride 、 三乙胺 、 间氯过氧苯甲酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 丙酮 、 mineral oil 为溶剂， 反应 23.42h， 生成 4-[(1RS)-1-(3,4-dichlorophenyl)-2-(methylsulfonyl)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

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.