2-{4-[4-(5-fluoro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]butyl}-2,3-dihydro-1H-isoindole-1,3-dione | 264869-71-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-{4-[4-(5-fluoro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]butyl}-2,3-dihydro-1H-isoindole-1,3-dione
• 英文别名: 2-{4-[4-(5-fluoro-1H-indol-3-yl)-3,6-dihydropyridin-1(2H)-yl]butyl}-1H-isoindole-1,3(2H)-dione；2-(4-(4-(5-Fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl)butyl)isoindoline-1,3-dione；2-[4-[4-(5-fluoro-1H-indol-3-yl)-3,6-dihydro-2H-pyridin-1-yl]butyl]isoindole-1,3-dione
• CAS: 264869-71-8
• 化学式: C₂₅H₂₄FN₃O₂
• 分子量: 417.483
• InChiKey: NECJNLXOJRDELU-UHFFFAOYSA-N

物化性质

• 沸点：
  621.9±55.0 °C(Predicted)
• 密度：
  1.309±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  56.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-{4-[4-(5-fluoro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]butyl}-2,3-dihydro-1H-isoindole-1,3-dione 在 甲胺 、 potassium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 16.0h， 生成 N-{4-[4-(5-fluoro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]butyl}-3-methylbenzene-1-sulfonamide
  参考文献：
  名称：

  Novel 3-(1,2,3,6-Tetrahydropyridin-4-yl)-1H-indole-Based Multifunctional Ligands with Antipsychotic-Like, Mood-Modulating, and Procognitive Activity

  摘要：

  The most troublesome aspects of behavioral and psychological symptoms of dementia (BPSD) are nowadays addressed by antidepressant, anxiolytic, and antipsychotic drugs, often administered off-label. Considering their modest effectiveness in dementia patients, the increased risk of adverse events and cognitive decline, there is an unmet need for well tolerated and effective therapy of BPSD. We designed and synthesized multifunctional ligands characterized in vitro as high affinity partial agonists of D2R, antagonists of 5-HT6R, and blockers of SERT. Moreover, the molecules activated 5-HT1AR and blocked 5-HT7R while having no relevant affinity for off-target M1R and hERG channel. Compound 16 (N-{244-(5-chloro-1H-iridol-3-y1)-1,2,3,6-tetrahydropyridin-l-yllethy1}-3-methylbenzene-l-sulfonamide), exhibited a broad antipsychotic-, antidepressant-, and anxiolytic-like activity, not eliciting motor impairments in mice. Most importantly, 16 showed memory-enhancing properties and it ameliorated memory deficits induced by scopolamine. The molecule outperformed most important comparators in selected tests, indicating its potential in the treatment of both cognitive and noncognitive (behavioral and psychological) symptoms of dementia.

  DOI：

  10.1021/acs.jmedchem.7b00839
• 作为产物：
  描述：

  N-(4-溴丁基)邻苯二甲酰亚胺 、 5-氟-3-(1,2,3,6-四氢吡啶-4-基)-1H-吲哚 在 N-(4-溴丁基)邻苯二甲酰亚胺 作用下， 以54的产率得到2-{4-[4-(5-fluoro-1H-indol-3-yl)-1,2,3,6-tetrahydropyridin-1-yl]butyl}-2,3-dihydro-1H-isoindole-1,3-dione
  参考文献：
  名称：

  3-Tetrahydropyridin-4-yl indoles for treatment of psychotic disorders

  摘要：

  本发明涉及以下化合物：其中所有变量均如规范中所定义。这些化合物对治疗精神疾病有用。

  公开号：

  US06391896B1

文献信息

• ARYLOSULFONAMIDES FOR THE TREATMENT OF CNS DISEASES
  申请人：Kolaczkowski Marcin

  公开号：US20130172365A1

  公开（公告）日：2013-07-04

  Arylsulphonamide derivatives of formula (I) and pharmaceutically acceptable salts thereof. The compounds may be useful for the treatment and/or prevention of disorders of the central nervous system.

  化学式（I）的芳基磺胺衍生物及其药用盐。这些化合物可能对中枢神经系统疾病的治疗和/或预防有用。
• Benzoate salt of 4-(5-methyl-oxazolo[4,5-b]-pyridin-2-yl)-1,4-diazabicyclo[3.2.2]nonane
  申请人：Duplantier Allen J.

  公开号：US20080045512A1

  公开（公告）日：2008-02-21

  The present invention provides a benzoate salt of Formula I: Formula I is also known as 4-(5-methyloxazolo[4,5-b]pyridine-2-yl)-1,4-diazabicyclo[3.2.2]nonane. The benzoate salt of the invention is useful in the treatment of schizophrenia and Alzheimer's Disease. It is particularly of use in the treatment of cognitive deficits associated with schizophrenia, cognitive and attention deficit symptoms of Alzheimer's Disease, and neurodegeneration associated with Alzheimer's Disease.

  本发明提供了一种公式I的苯甲酸盐： 公式I也被称为4-(5-甲氧噁唑[4,5-b]吡啶-2-基)-1,4-二氮杂双环[3.2.2]壬烷。该发明的苯甲酸盐在治疗精神分裂症和阿尔茨海默病方面非常有用。它特别适用于治疗与精神分裂症相关的认知缺陷，阿尔茨海默病的认知和注意力缺陷症状，以及与阿尔茨海默病相关的神经退行性。
• Azabenzoxazoles for the treatment of CNS disorders
  申请人：Rogers N. Bruce

  公开号：US20060166974A1

  公开（公告）日：2006-07-27

  The present invention relates to α7 nicotinic receptor agonists of formula I as described herein and to a method for treating disorders of the Central Nervous System (CNS) such as cognitive deficits in schizophrenia, by administering to a mammal an α7 nicotinic receptor agonist of formula I as shown herein.

  本发明涉及如下式所述的α7烟碱受体激动剂，以及通过向哺乳动物施用本文所示的α7烟碱受体激动剂来治疗中枢神经系统（CNS）疾病，如精神分裂症中的认知缺陷的方法。
• Cyclopentapyridine and tetrahydroquinoline derivatives
  申请人：Lefker A. Bruce

  公开号：US20060247254A1

  公开（公告）日：2006-11-02

  6,7-Dihydro-5H-cyclopenta[b]pyridine and 5,6,7,8-tetrahydroquinoline compounds of Formula (I), including salts, hydrates and solvates thereof, that act as 5-HT 2 receptor ligands and their uses in the treatment of diseases linked to the activation of 5-HT 2c receptors are described herein.

  本文介绍了公式(I)中的6,7-二氢-5H-环戊[b]吡啶和5,6,7,8-四氢喹啉化合物，包括其盐、水合物和溶剂化物，它们作为5-HT2受体配体，并且它们在治疗与5-HT2受体激活有关的疾病方面的用途。
• Tartrate Salt of (7S)-7-[(5-Fluoro-2-Methyl-Benzyl)oxy]-2-[(2R)-2-Methylpiperazin-1-YL]-6,7-Dihydro-5H-Cyclopenta[B]Pyridine
  申请人：Liu Kevin Kun-Chin

  公开号：US20100004259A1

  公开（公告）日：2010-01-07

  The present invention provides a tartrate salt of Formula (I), Formula I is also known as (7S)-7-[(5-fluoro-2-methyl-benzyl)oxy]-2-[(2R)-2-methylpiperazin-1-yl]-6,7-dihydro-5H-cyclopenta[b]pyridine. The tartrate salt is preferably crystalline. The tartrate salt of Formula I of the invention is useful in the treatment of diseases linked to activation of the 5HT2c receptor in animals including humans, for example, in the treatment of schizophrenia, cognitive deficits including cognitive deficits associated with schizophrenia, anxiety, depression, obsessive-compulsive disorder, epilepsy, obesity, sexual dysfunction, and urinary incontinence, among others.

  本发明提供了公式（I）的酒石酸盐，公式I也被称为（7S）-7-[(5-氟-2-甲基苯基)氧基]-2-[(2R)-2-甲基哌嗪-1-基]-6,7-二氢-5H-环戊[b]吡啶。该酒石酸盐最好是结晶性的。本发明的公式I的酒石酸盐对于治疗与动物包括人类的5HT2c受体激活有关的疾病非常有用，例如治疗精神分裂症、认知缺陷包括与精神分裂症有关的认知缺陷、焦虑症、抑郁症、强迫症、癫痫、肥胖症、性功能障碍和尿失禁等。