7-methoxy-1H-indole-6-carboxylic acid | 1400093-69-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 7-methoxy-1H-indole-6-carboxylic acid
• CAS: 1400093-69-7
• 化学式: C₁₀H₉NO₃
• 分子量: 191.186
• InChiKey: ZTYZKFMWBVTGQW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  62.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  7-methoxy-1H-indole-6-carboxylic acid 在 草酰氯 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 7-methoxy-1H-indole-6-carbonyl chloride
  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 硫酸 、 palladium on activated charcoal 、 水 、 氢气 、 溴 、 硝酸 、 potassium carbonate 、 一水合肼 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.0h， 生成 7-methoxy-1H-indole-6-carboxylic acid
  参考文献：
  名称：

  含三氮唑稠环类衍生物、药物组合物及其制备方法和应用

  摘要：

  本发明涉及含三氮唑稠环类衍生物、其药物组合物及其制备方法和应用。特别地，本发明涉及通式(I)所示的化合物、其制备方法及含有该化合物的药物组合物，及其作为NK‑3受体拮抗剂，在治疗和/或预防一系列广泛的CNS和外周疾病等疾病或病症的用途，其中通式(I)中的各取代基与说明书中的定义相同。

  公开号：

  CN115260180A

文献信息

• 含三氮唑稠环类衍生物、药物组合物及其制备方法和应用
  申请人：长春金赛药业有限责任公司

  公开号：CN115260180A

  公开（公告）日：2022-11-01

  本发明涉及含三氮唑稠环类衍生物、其药物组合物及其制备方法和应用。特别地，本发明涉及通式(I)所示的化合物、其制备方法及含有该化合物的药物组合物，及其作为NK‑3受体拮抗剂，在治疗和/或预防一系列广泛的CNS和外周疾病等疾病或病症的用途，其中通式(I)中的各取代基与说明书中的定义相同。
• Optimization of a Small Tropomyosin-Related Kinase B (TrkB) Agonist 7,8-Dihydroxyflavone Active in Mouse Models of Depression
  作者：Xia Liu、Chi-Bun Chan、Qi Qi、Ge Xiao、Hongbo R. Luo、Xiaolin He、Keqiang Ye

  DOI：10.1021/jm301099x

  日期：2012.10.11

  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.