methyl 2-methoxy-4,5-dimethylbenzoate | 1245534-33-1

• 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: methyl 2-methoxy-4,5-dimethylbenzoate
• CAS: 1245534-33-1
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: FEKLTHCADUIRNW-UHFFFAOYSA-N

物化性质

• 沸点：
  297.7±35.0 °C(Predicted)
• 密度：
  1.056±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 海关编码：
  2918990090

反应信息

• 作为反应物：
  描述：

  methyl 2-methoxy-4,5-dimethylbenzoate 在 硫酸 、 硝酸 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 (E)-methyl 4-(2-(dimethylamino)vinyl)-2-methoxy-5-methyl-3-nitrobenzoate
  参考文献：
  名称：

  Optimization of a Small Tropomyosin-Related Kinase B (TrkB) Agonist 7,8-Dihydroxyflavone Active in Mouse Models of Depression

  摘要：

  Structure-activity relationship study shows that the catechol group in 7,8-dihdyroxyflavone, a selective small TrkB receptor agonist, is critical for agonistic activity. To improve the poor pharmacolcinetic profiles intrinsic to catechol-containing molecules and to elevate the agonistic effect of the lead compound, we initiated the lead optimization campaign by synthesizing various bioisosteric derivatives. Here we show that the optimized 2-methyl-8-(4'-(pyrrolidin-l-yl)phenyl)chromeno[7,8-d]imidazol-6(1H)-one derivative possesses enhanced TrkB stimulatory activity. Chronic oral administration of this compound significantly reduces the immobility in forced swim test and tail suspension test, two classical antidepressant behavioral animal models, which is accompanied by robust TrkB activation in hippocampus of mouse brain. Further, in vitro ADMET studies demonstrate that this compound possesses the improved features compared to the previous lead compound. Hence, this optimized compound may act as a promising lead candidate for in-depth drug development for treating various neurological disorders including depression.

  DOI：

  10.1021/jm301099x
• 作为产物：
  描述：

  4-甲基水杨酸 在 N-氯代丁二酰亚胺 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 methyl 2-methoxy-4,5-dimethylbenzoate
  参考文献：
  名称：

  Optimization of a Small Tropomyosin-Related Kinase B (TrkB) Agonist 7,8-Dihydroxyflavone Active in Mouse Models of Depression

  摘要：

  Structure-activity relationship study shows that the catechol group in 7,8-dihdyroxyflavone, a selective small TrkB receptor agonist, is critical for agonistic activity. To improve the poor pharmacolcinetic profiles intrinsic to catechol-containing molecules and to elevate the agonistic effect of the lead compound, we initiated the lead optimization campaign by synthesizing various bioisosteric derivatives. Here we show that the optimized 2-methyl-8-(4'-(pyrrolidin-l-yl)phenyl)chromeno[7,8-d]imidazol-6(1H)-one derivative possesses enhanced TrkB stimulatory activity. Chronic oral administration of this compound significantly reduces the immobility in forced swim test and tail suspension test, two classical antidepressant behavioral animal models, which is accompanied by robust TrkB activation in hippocampus of mouse brain. Further, in vitro ADMET studies demonstrate that this compound possesses the improved features compared to the previous lead compound. Hence, this optimized compound may act as a promising lead candidate for in-depth drug development for treating various neurological disorders including depression.

  DOI：

  10.1021/jm301099x

文献信息

• 作为神经保护剂的药用化合物
  申请人：江苏先声药业有限公司

  公开号：CN104045552B

  公开（公告）日：2019-06-11

  本发明公开了一类作为神经保护剂的药用化合物，其为神经元型一氧化氮合酶‑突触后密度蛋白‑95（nNOS‑PSD95）的解耦联剂，其为具有通式（Ⅰ）苯环衍生物或其药学上可接受的盐。本申请进一步公开了该类化合物的制备方法以及其用于预防和治疗受神经元损伤影响引起的疾病的用途。