methyl [3-(3-hydroxypropoxy)phenyl]acetate

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl [3-(3-hydroxypropoxy)phenyl]acetate
• 英文别名: Methyl 2-(3-(3-hydroxypropoxy)phenyl)acetate；methyl 2-[3-(3-hydroxypropoxy)phenyl]acetate
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: AACYZCLCRRDLCO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl [3-(3-hydroxypropoxy)phenyl]acetate 在 sodium chlorite 、 sodium chloride dihydrate 、 2,2,6,6-四甲基哌啶氧化物 作用下， 以 乙腈 为溶剂， 反应 3.5h， 以99%的产率得到3-[3-(2-methoxy-2-oxoethyl)phenoxy]propanoic acid
  参考文献：
  名称：

  Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity

  摘要：

  We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex. (c) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.02.008
• 作为产物：
  描述：

  3-羟基苯乙酸甲酯 、 3-溴-1-丙醇 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 14.0h， 以62%的产率得到methyl [3-(3-hydroxypropoxy)phenyl]acetate
  参考文献：
  名称：

  Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity

  摘要：

  We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex. (c) 2018 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2018.02.008

文献信息

• Discovery of DSP-1053, a novel benzylpiperidine derivative with potent serotonin transporter inhibitory activity and partial 5-HT1A receptor agonistic activity
  作者：Hidefumi Yoshinaga、Tomoaki Nishida、Izumi Sasaki、Taro Kato、Hitomi Oki、Kazuki Yabuuchi、Tomohiro Toyoda

  DOI：10.1016/j.bmc.2018.02.008

  日期：2018.5

  We have previously shown that SMP-304, a serotonin uptake inhibitor with weak 5-HT1A partial agonistic activity, may act under high serotonin levels as a 5-HT1A antagonist that improves the onset of paroxetine in the rat swimming test. However, SMP-304 is mostly metabolized by CYP2D6, indicating limited efficacy among individuals and increased side effects. To reduce CYP2D6 metabolic contribution and enhance SERT/5-HT1A binding affinity, we carried out a series of substitutions at the bromine atom in the left part of the benzene ring of SMP-304 and replaced the right part of SMP-304 with a chroman4-one. This optimization work led to the identification of the antidepressant candidate DSP-1053 as a potent SERT inhibitor with partial 5-HT1A receptor agonistic activity. DSP-1053 showed low CYP2D6 metabolic contribution and a robust increase in serotonin levels in the rat frontal cortex. (c) 2018 Elsevier Ltd. All rights reserved.