(-)-(S)-4-methyl-1-[3-(4-chlorophenoxy)-2-methyl-propyl]piperidine

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (-)-(S)-4-methyl-1-[3-(4-chlorophenoxy)-2-methyl-propyl]piperidine
• 英文别名: 1-[(2S)-3-(4-chlorophenoxy)-2-methylpropyl]-4-methylpiperidine
• 化学式: C₁₆H₂₄ClNO
• 分子量: 281.826
• InChiKey: BFHSZXRJQFTQDS-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  (+)-(S)-3-(4-chlorophenoxy)-2-methyl-1-propanol 在 sodium hydroxide 、 三乙胺 作用下， 以 二氯甲烷 、 异丙醇 为溶剂， 反应 8.17h， 生成 (-)-(S)-4-methyl-1-[3-(4-chlorophenoxy)-2-methyl-propyl]piperidine
  参考文献：
  名称：

  Synthesis of Chiral 1-[ω-(4-Chlorophenoxy)alkyl]-4-methylpiperidines and Their Biological Evaluation at σ₁, σ₂, and Sterol Δ₈−Δ₇ Isomerase Sites

  摘要：

  Sumitomo's patented sigma ligand 1-[3-(4-chlorophenoxy)propyll-4-methylpiperidine (15), which has been claimed as agent for CNS disorders and neuropathies, and its lower homologue 12 were prepared along with related chiral (4-chlorophenoxy)alkylpiperidines. They were tested at sigma(1), sigma(2), and sterol Delta(8)-Delta(7) isomerase (SI) sites by in vitro radioligand binding assays, to evaluate the influence of a chiral center in the alkyl chain on the selective a, binding relative to other a family sites. Generally high alpha(1)-site affinities were found, so that the chirality introduced by a methyl substitution resulted in slight differences. Nevertheless, the shorter oxyethylenic chain was beneficial to increase a, selectivity. However, the (-)-(S)-4-methyl-1-[2-(4-chlorophenoxy)1-methylethyl]piperidine ((-)-(S)-17) reached the highest sigma(1) affinity (K-i = 0.34 nM) and the best selectivity relative to the sigma(2) site (547-fold). Compound (-)-(S)-17 displayed also a moderate selectivity (11-fold) relative to the SI site.

  DOI：

  10.1021/jm021014d

文献信息

• Synthesis of Chiral 1-[ω-(4-Chlorophenoxy)alkyl]-4-methylpiperidines and Their Biological Evaluation at σ₁, σ₂, and Sterol Δ₈−Δ₇ Isomerase Sites
  作者：Francesco Berardi、Fulvio Loiodice、Giuseppe Fracchiolla、Nicola Antonio Colabufo、Roberto Perrone、Vincenzo Tortorella

  DOI：10.1021/jm021014d

  日期：2003.5.1

  Sumitomo's patented sigma ligand 1-[3-(4-chlorophenoxy)propyll-4-methylpiperidine (15), which has been claimed as agent for CNS disorders and neuropathies, and its lower homologue 12 were prepared along with related chiral (4-chlorophenoxy)alkylpiperidines. They were tested at sigma(1), sigma(2), and sterol Delta(8)-Delta(7) isomerase (SI) sites by in vitro radioligand binding assays, to evaluate the influence of a chiral center in the alkyl chain on the selective a, binding relative to other a family sites. Generally high alpha(1)-site affinities were found, so that the chirality introduced by a methyl substitution resulted in slight differences. Nevertheless, the shorter oxyethylenic chain was beneficial to increase a, selectivity. However, the (-)-(S)-4-methyl-1-[2-(4-chlorophenoxy)1-methylethyl]piperidine ((-)-(S)-17) reached the highest sigma(1) affinity (K-i = 0.34 nM) and the best selectivity relative to the sigma(2) site (547-fold). Compound (-)-(S)-17 displayed also a moderate selectivity (11-fold) relative to the SI site.