7-methoxy-1H-indole-6-carbonyl chloride | 1400093-70-0

• 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-carbonyl chloride
• 英文别名: 7-methoxy-6-indoloyl chloride
• CAS: 1400093-70-0
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.632
• InChiKey: YEJYWFDRROAJKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 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：
  42.1
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  7-methoxy-1H-indole-6-carbonyl chloride 在 氢溴酸 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 2-(4-(pyrrolidin-1-yl)phenyl)pyrano[3,2-g]indol-4(9H)-one
  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 、 草酰氯 、 硫酸 、 水 、 氢气 、 硝酸 、 palladium(II) hydroxide 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 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

文献信息

• [EN] HETEROCYCLIC FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO<br/>[FR] DÉRIVÉS HÉTÉROCYCLIQUES DE FLAVONE, COMPOSITIONS ET PROCÉDÉS S'Y RAPPORTANT
  申请人：UNIV EMORY

  公开号：WO2014018741A1

  公开（公告）日：2014-01-30

  In certain embodiments, the disclosure relates to heterocyclic flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of 5 treating or preventing diseases or conditions related to BDNF and TrkB activity, such as depression, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof.

  在某些实施例中，该公开涉及杂环黄酮衍生物，例如本文提供的公式所描述的那些，药物组合物以及相关方法。在某些实施例中，该公开涉及治疗或预防与BDNF和TrkB活性相关的疾病或症状的方法，例如抑郁症、中风、雷特综合征、帕金森病和阿尔茨海默病，通过向需要的受试者施用包含本文所披露的化合物的药物组合物的有效剂量。
• HETEROCYCLIC FLAVONE DERIVATIVES, COMPOSITIONS, AND METHODS RELATED THERETO
  申请人：EMORY UNIVERSITY

  公开号：US20150191481A1

  公开（公告）日：2015-07-09

  In certain embodiments, the disclosure relates to heterocyclic flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of 5 treating or preventing diseases or conditions related to BDNF and TrkB activity, such as depression, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein to a subject in need thereof.

  在某些实施方式中，本公开涉及杂环类黄酮衍生物，例如所述的公式所描述的那些，以及与之相关的药物组合物和方法。在某些实施方式中，本公开涉及通过向需要治疗或预防与BDNF和TrkB活性有关的疾病或病况，例如抑郁症、中风、雷特综合征、帕金森病和阿尔茨海默病的患者施用包含本文所披露的化合物的有效量的药物组合物的方法。
• Heterocyclic flavone derivatives, compositions, and methods related thereto
  申请人：Emory University

  公开号：US10010526B2

  公开（公告）日：2018-07-03

  In certain embodiments, the disclosure relates to heterocyclic flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as depression, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein.

  在某些实施方案中，本公开涉及杂环黄酮衍生物，如本文提供的式中描述的那些衍生物、药物组合物及其相关方法。在某些实施方案中，本公开涉及通过施用有效量的包含本文所公开化合物的药物组合物来治疗或预防与 BDNF 和 TrkB 活性有关的疾病或病症的方法，如抑郁症、中风、Rett 综合征、帕金森病和阿尔茨海默病。
• Heterocyclic Flavone Derivatives, Compositions, and Methods Related Thereto
  申请人：Emory University

  公开号：US20170165225A1

  公开（公告）日：2017-06-15

  In certain embodiments, the disclosure relates to heterocyclic flavone derivatives, such as those described by formula provided herein, pharmaceutical compositions, and methods related thereto. In certain embodiments, the disclosure relates to methods of treating or preventing diseases or conditions related to BDNF and TrkB activity, such as depression, stroke, Rett syndrome, Parkinson's disease, and Alzheimer's disease by administering effective amounts of pharmaceutical compositions comprising compounds disclosed herein.
• US9593125B2
  申请人：——

  公开号：US9593125B2

  公开（公告）日：2017-03-14