Datelliptium | 81531-57-9

• 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: Datelliptium
• 英文别名: 2-[2-(diethylamino)ethyl]-5,11-dimethyl-6H-pyrido[4,3-b]carbazol-2-ium-9-ol
• CAS: 81531-57-9
• 化学式: C23H28N3O+
• 分子量: 362.5
• InChiKey: NGOHTJBYABHJKF-UHFFFAOYSA-O

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  43.1
• 氢给体数：
  2
• 氢受体数：
  2

文献信息

• SMALL MOLECULES TARGETING REPEAT r(CGG) SEQUENCES
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US20150307487A1

  公开（公告）日：2015-10-29

  The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5′C G /3′G G C motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5′C G G/3′G G C motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp. Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp-protein aggregates.

  这项发明提供了一系列针对扩增的r(CGG)重复序列的生物活性小分子，称为r(CGG)exp，导致脆性X相关性震颤共济失调综合征（FXTAS）。该化合物是通过利用相互作用的化学类型和RNA基序的信息来鉴定的。具体来说，9-羟基-5,11-二甲基-2-(2-(哌啶-1-基)乙基)-6H-吡啶并[4,3-b]咔唑-2-离子，结合r(CGG)exp中的5′CG/3′GGC基序，并破坏有毒的r(CGG)exp-蛋白质复合物。具体来说，结合了两个9-羟基椭圆咔啉类似结构的二聚化合物甚至可以更有效地结合r(CGG)exp中的5′CGG/3′GGC基序，并破坏有毒的r(CGG)exp-蛋白质复合物。结构活性关系（SAR）研究确定了烷基化的吡啶基和酚基侧链是驱动对r(CGG)重复序列，如r(CGG)exp的分子识别的重要化学类型。重要的是，该化合物在FXTAS模型细胞系统中表现出疗效，表现为改善FXTAS相关的前mRNA剪接缺陷，并减少r(CGG)exp-蛋白质聚集物的大小和数量。
• Small molecules targeting repeat r(CGG) sequences
  申请人：THE SCRIPPS RESEARCH INSTITUTE

  公开号：US10011598B2

  公开（公告）日：2018-07-03

  The invention provides a series of bioactive small molecules that target expanded r(CGG) repeats, termed r(CGG)exp, that causes Fragile X-associated Tremor Ataxia Syndrome (FXTAS). The compound was identified by using information on the chemotypes and RNA motifs that interact. Specifically, 9-hydroxy-5,11-dimethyl-2-(2-(piperidin-1-yl)ethyl)-6H-pyrido[4,3-b]carbazol-2-ium, binds the 5′CGG/3′GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Specifically, dimeric compounds incorporating two 9-hydroxyellipticine analog structures can even more potently bind the 5′CGG/3′GGC motifs in r(CGG)exp and disrupts a toxic r(CGG)exp-protein complex. Structure-activity relationships (SAR) studies determined that the alkylated pyridyl and phenolic side chains are important chemotypes that drive molecular recognition of r(CGG) repeats, such as r(CGG)exp. Importantly, the compound is efficacious in FXTAS model cellular systems as evidenced by its ability to improve FXTAS-associated pre-mRNA splicing defects and to reduce the size and number of r(CGG)exp-protein aggregates.

  本发明提供了一系列针对导致脆性 X 相关震颤共济失调综合征（FXTAS）的扩展 r(CGG)重复序列（称为 r(CGG)exp）的生物活性小分子。该化合物是通过化学型和相互作用的 RNA 基团信息确定的。具体来说，9-羟基-5,11-二甲基-2-(2-(哌啶-1-基)乙基)-6H-吡啶并[4,3-b]咔唑-2-鎓能与 r(CGG)exp 中的 5′CGG/3′GGC 基序结合，并破坏有毒的 r(CGG)exp 蛋白复合物。具体来说，含有两个 9-羟基鞣花碱类似物结构的二聚化合物能更有效地结合 r(CGG)exp 中的 5′CGG/3′GGC 基序，并破坏具有毒性的 r(CGG)exp 蛋白复合物。结构-活性关系（SAR）研究确定，烷基化的吡啶基和酚类侧链是驱动分子识别 r(CGG)exp 等 r(CGG) 重复序列的重要化学型。重要的是，该化合物在 FXTAS 模型细胞系统中具有疗效，这体现在它能够改善 FXTAS 相关的前核糖核酸剪接缺陷，并减少 r(CGG)exp 蛋白聚集体的大小和数量。
• METHODS AND COMPOUNDS FOR REGULATING APOPTOSIS
  申请人：Reed John C.

  公开号：US20090118135A1

  公开（公告）日：2009-05-07

  An assay for determining compounds that inhibit activity of a BCl-2 protein, or affect conversion of Bcl-2 from an antiapoptotic to a proapoptotic form are described. In addition, compounds that modulate the function of anti-apoptotic proteins such as Bcl-2 and related Bcl-2 family members are identified.
• ANTIANGIOGENIC SMALL MOLECULES AND METHODS OF USE
  申请人：Zudaire Enrique

  公开号：US20120129775A1

  公开（公告）日：2012-05-24

  Methods of inhibiting undesired angiogenesis are provided, which methods include administering to a subject a therapeutically effective amount of at least one of the compounds described herein, or a pharmaceutically acceptable salt thereof.
• US9186365B2
  申请人：——

  公开号：US9186365B2

  公开（公告）日：2015-11-17