N-(2-(diethylamino)ethyl)-2,3-dimethyl-1H-indole-5-carboxamide

• 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: N-(2-(diethylamino)ethyl)-2,3-dimethyl-1H-indole-5-carboxamide
• 英文别名: N-[2-(diethylamino)ethyl]-2,3-dimethyl-1H-indole-5-carboxamide
• 化学式: C₁₇H₂₅N₃O
• 分子量: 287.405
• InChiKey: BFLGNTQXFKCKGK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  48.1
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  4-肼基苯甲酸 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 112.0h， 生成 N-(2-(diethylamino)ethyl)-2,3-dimethyl-1H-indole-5-carboxamide
  参考文献：
  名称：

  [EN] INDOLE COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES
  [FR] COMPOSÉS D'INDOLE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES

  摘要：

  提供了治疗多聚Q疾病或障碍，如亨廷顿病的方法。本公开的化合物(I)的公式能够直接结合到突变的亨廷蛋白质的多聚Q片段。这种结合至少部分地逆转了突变的亨廷蛋白质的构象，使其恢复成野生型亨廷蛋白质。这种结合还促进了自噬对于错误折叠和/或突变蛋白质（如突变的亨廷蛋白质）的清除。

  公开号：

  WO2021173593A1

文献信息

• [EN] INDOLE COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES<br/>[FR] COMPOSÉS D'INDOLE POUR LE TRAITEMENT DE MALADIES NEURODÉGÉNÉRATIVES
  申请人：GALYAN BIO INC

  公开号：WO2021173593A1

  公开（公告）日：2021-09-02

  Methods of treating polyQ diseases or disorders such as Huntington's Disease are presented. Compounds of formula (I) of the disclosure are capable of binding directly to the polyQ segment of mutated huntingtin. This binding results in at least partial reversal of the conformation of mutated huntingtin to wild type huntingtin. The binding also facilitates autophagic removal of misfolded and/or mutated proteins such as mutated huntingtin.

  提供了治疗多聚Q疾病或障碍，如亨廷顿病的方法。本公开的化合物(I)的公式能够直接结合到突变的亨廷蛋白质的多聚Q片段。这种结合至少部分地逆转了突变的亨廷蛋白质的构象，使其恢复成野生型亨廷蛋白质。这种结合还促进了自噬对于错误折叠和/或突变蛋白质（如突变的亨廷蛋白质）的清除。
• [EN] PROTEIN-OLIGOMER BINDING AGENTS AND THERAPEUTIC USES THEREOF<br/>[FR] AGENTS SE LIANT À L'OLIGOMÈRE PROTÉIQUE ET LEURS UTILISATIONS THÉRAPEUTIQUES
  申请人：[en]GALYAN BIO, INC.

  公开号：WO2023025915A1

  公开（公告）日：2023-03-02

  The present invention is based on the finding that the compounds disclosed herein bind to, preferably harmful, protein-oligomers and thereby induce a conformational change of the latter. This conformational change enhances the recognition of the protein oligomers by cellular degradation mechanisms, such as autophagy and the ubiquitin proteasome system which in turn causes an increased degradation of such, usually undesireous, protein-oligomers. Hence, in a first aspect, the invention pertains to a protein-oligomer aggregation-agent, wherein the protein-oligomer aggregation-agent comprises, or is selected from, a small molecule, an antibody, a nanoparticle, a nucleic acid, a peptide and/or a therapeutic protein. The invention provides therapeutic applications of the disclosed compounds in the treatment and/or prevention of disorders associated with the presence of one or more of such oligomeric structures, preferably of protein-oligomers. The invention intends to induce aggregation of harmful oligomers and thereby induce cellular systemic mechansims that recognize and degrade structurally larger aggregates.