3-(1-甲基-2-吡咯烷基)-1H-吲哚 | 7236-83-1

• 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
• 中文名称: 3-(1-甲基-2-吡咯烷基)-1H-吲哚
• 英文名称: 3-(1-methylpyrrolidin-2-yl)-1H-indole
• 英文别名: 3-(1-methyl-pyrrolidin-2-yl)-indole；3-(1-Methyl-2-pyrrolidinyl)-indol；3-(1-Methyl-2-pyrrolidinyl)indol；3-(1-Methyl-2-pyrrolidinyl)indole
• CAS: 7236-83-1
• 化学式: C₁₃H₁₆N₂
• 分子量: 200.283
• InChiKey: FNTDGCHSJHAFAV-UHFFFAOYSA-N

物化性质

• 沸点：
  328.02°C (rough estimate)
• 密度：
  1.0701 (rough estimate)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  19
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-(1-甲基-2-吡咯烷基)-1H-吲哚 在 potassium cyanide 、 羟胺 、 sodium hydride 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 24.75h， 生成 (±)-N-hydroxy-4-((3-(1-methylpyrrolidin-2-yl)-1H-indol-1-yl)methyl)benzamide
  参考文献：
  名称：

  Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated

  摘要：

  The discovery of isozyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biological functions of individual HDACs and for validating HDACs as drug targets. The isozyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no studies toward selective HDAC10 inhibitors have been published. Using two complementary assays, we found Tubastatin A, an HDAC6 inhibitor, to potently bind HDAC10. We synthesized Tubastatin A derivatives and found that a basic amine in the cap group was required for strong HDAC10 binding. HDAC10 inhibitors mimicked knockdown by causing dose-dependent accumulation of acidic vesicles in a neuroblastoma cell line. Furthermore, docking into human HDAC10 homology models indicated that a hydrogen bond between a cap group nitrogen and the gatekeeper residue Glu272 was responsible for potent HDAC10 binding. Taken together, our data provide an optimal platform for the development of HDAC10-selective inhibitors, as exemplified with the Tubastatin A scaffold.

  DOI：

  10.1021/acs.jmedchem.8b01936
• 作为产物：
  描述：

  (Z)-3-(1-methylpyrrolidin-2-ylidene)-3H-indole 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 以83%的产率得到3-(1-甲基-2-吡咯烷基)-1H-吲哚
  参考文献：
  名称：

  Selective Inhibition of Histone Deacetylase 10: Hydrogen Bonding to the Gatekeeper Residue is Implicated

  摘要：

  The discovery of isozyme-selective histone deacetylase (HDAC) inhibitors is critical for understanding the biological functions of individual HDACs and for validating HDACs as drug targets. The isozyme HDAC10 contributes to chemotherapy resistance and has recently been described to be a polyamine deacetylase, but no studies toward selective HDAC10 inhibitors have been published. Using two complementary assays, we found Tubastatin A, an HDAC6 inhibitor, to potently bind HDAC10. We synthesized Tubastatin A derivatives and found that a basic amine in the cap group was required for strong HDAC10 binding. HDAC10 inhibitors mimicked knockdown by causing dose-dependent accumulation of acidic vesicles in a neuroblastoma cell line. Furthermore, docking into human HDAC10 homology models indicated that a hydrogen bond between a cap group nitrogen and the gatekeeper residue Glu272 was responsible for potent HDAC10 binding. Taken together, our data provide an optimal platform for the development of HDAC10-selective inhibitors, as exemplified with the Tubastatin A scaffold.

  DOI：

  10.1021/acs.jmedchem.8b01936

文献信息

• Salts of (R)-5-(2phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole, 5-bromo-3-[(R)-1-methyl-pyrrolidin-2-ylmethyl]-1H-indole and of eletriptan
  申请人：KANSAL Vinod Kumar

  公开号：US20090299077A1

  公开（公告）日：2009-12-03

  The present invention relates to salts of (R)-5-(2-phenylsulphonylethenyl)-3-(N-methylpyrrolidin-2-ylmethyl)-1H-indole of the formula: wherein HX is an acid selected from para-toluene sulfonic acid, benzene sulphonic acid, trifluoroacetic acid, methane sulphonic acid, formic acid and succinic acid; and to processes of preparing and using such salts.

  这项发明涉及以下化学式的(R)-5-(2-苯磺酰乙烯基)-3-(N-甲基吡咯烷-2-基甲基)-1H-吲哚的盐： 其中HX是从对甲苯磺酸、苯磺酸、三氟乙酸、甲磺酸、甲酸和琥珀酸中选择的酸；以及制备和使用这种盐的方法。
• [EN] RORγ MODULATORS<br/>[FR] MODULATEURS DE ROR&Ggr;
  申请人：BRISTOL MYERS SQUIBB CO

  公开号：WO2015035278A1

  公开（公告）日：2015-03-12

  Described are RORγ modulators of the formula (I), or pharmaceutically acceptable salts thereof, wherein all substituents are defined herein. The invention includes stereoisomeric forms of the compounds of formula I, including stereoisomerically-pure, scalemic and racemic form, as well as tautomers thereof. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.

  描述了公式（I）的RORγ调节剂，或其药学上可接受的盐，其中所有取代基在此处定义。该发明包括公式I化合物的立体异构体形式，包括立体异构纯、立体混合和消旋形式，以及其互变异构体。还提供了包含相同化合物的药物组合物。这些化合物和组合物在调节细胞中的RORγ活性的方法以及治疗患有疾病或紊乱的受试者的方法中是有用的，其中受试者在调节RORγ活性方面会从中获益，例如自身免疫和/或炎症性疾病。
• AZOLECARBOXAMIDE COMPOUND OR SALT THEREOF
  申请人：Astellas Pharma Inc.

  公开号：EP2206707B1

  公开（公告）日：2014-07-23
• RORy MODULATORS
  申请人：BRISTOL-MYERS SQUIBB COMPANY

  公开号：US20160318870A1

  公开（公告）日：2016-11-03

  Described are RORγ modulators of the formula (I), or pharmaceutically acceptable salts thereof, wherein all substituents are defined herein. The invention includes stereoisomeric forms of the compounds of formula I, including stereoisomerically-pure, scalemic and racemic form, as well as tautomers thereof. Also provided are pharmaceutical compositions comprising the same. Such compounds and compositions are useful in methods for modulating RORγ activity in a cell and methods for treating a subject suffering from a disease or disorder in which the subject would therapeutically benefit from modulation of RORγ activity, for example, autoimmune and/or inflammatory disorders.
• US8304547B2
  申请人：——

  公开号：US8304547B2

  公开（公告）日：2012-11-06