methyl 3-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-4-methoxybenzoate | 1609477-87-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 3-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-4-methoxybenzoate
• CAS: 1609477-87-3
• 化学式: C₂₆H₃₄O₇
• 分子量: 458.552
• InChiKey: SKLJMDXNUJDFSZ-UHFFFAOYSA-N

物化性质

• 沸点：
  608.8±55.0 °C(predicted)
• 密度：
  1.130±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.35
• 重原子数：
  33.0
• 可旋转键数：
  11.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  91.29
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 3-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-4-methoxybenzoate 在 potassium hydroxide 、 盐酸 作用下， 以 1,4-二氧六环 、 水 、 二氯甲烷 为溶剂， 反应 12.0h， 以0.27 g的产率得到3-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)-butoxy)-4-methoxybenzoic acid
  参考文献：
  名称：

  Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu_2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence

  摘要：

  As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu(2) receptor PAMs and no activity at mGlu(3). Compound optimization led to the identification of potent mGlu(2/3) selective PAMs with no in vitro activity at mGlu(1,4-8) or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu(2) and PAM activity at mGlu(3). The most potent mGlu(2/3) PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu(2/3) PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu(2/3) receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.

  DOI：

  10.1021/jm5000563
• 作为产物：
  描述：

  3,3-二甲基-1-丁酸 在 aluminum (III) chloride 、 草酰氯 、 potassium carbonate 、 potassium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 12.25h， 生成 methyl 3-(4-(4-(3,3-dimethylbutanoyl)-3-hydroxy-2-methylphenoxy)butoxy)-4-methoxybenzoate
  参考文献：
  名称：

  Design and Synthesis of Systemically Active Metabotropic Glutamate Subtype-2 and -3 (mGlu_2/3) Receptor Positive Allosteric Modulators (PAMs): Pharmacological Characterization and Assessment in a Rat Model of Cocaine Dependence

  摘要：

  As part of our ongoing small-molecule metabotropic glutamate (mGlu) receptor positive allosteric modulator (PAM) research, we performed structure activity relationship (SAR) studies around a series of group II mGlu PAMs. Initial analogues exhibited weak activity as mGlu(2) receptor PAMs and no activity at mGlu(3). Compound optimization led to the identification of potent mGlu(2/3) selective PAMs with no in vitro activity at mGlu(1,4-8) or 45 other CNS receptors. In vitro pharmacological characterization of representative compound 44 indicated agonist-PAM activity toward mGlu(2) and PAM activity at mGlu(3). The most potent mGlu(2/3) PAMs were characterized in assays predictive of ADME/T and pharmacokinetic (PK) properties, allowing the discovery of systemically active mGlu(2/3) PAMs. On the basis of its overall profile, compound 74 was selected for behavioral studies and was shown to dose-dependently decrease cocaine self-administration in rats after intraperitoneal administration. These mGlu(2/3) receptor PAMs have significant potential as small molecule tools for investigating group II mGlu pharmacology.

  DOI：

  10.1021/jm5000563