tert-butyl 4-(3-formyl-1-tosyl-1H-indol-4-yl)piperazine-1-carboxylate | 1258408-27-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: tert-butyl 4-(3-formyl-1-tosyl-1H-indol-4-yl)piperazine-1-carboxylate
• 英文别名: tert-butyl 4-[3-formyl-1-(toluene-4-sulfonyl)-1H-indol-4-yl]piperazine-1-carboxylate；Tert-butyl 4-[3-formyl-1-(4-methylphenyl)sulfonylindol-4-yl]piperazine-1-carboxylate；tert-butyl 4-[3-formyl-1-(4-methylphenyl)sulfonylindol-4-yl]piperazine-1-carboxylate
• CAS: 1258408-27-3
• 化学式: C₂₅H₂₉N₃O₅S
• 分子量: 483.588
• InChiKey: AMTWZZHHNSCGJT-UHFFFAOYSA-N

物化性质

• 沸点：
  672.1±65.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  97.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tert-butyl 4-(3-formyl-1-tosyl-1H-indol-4-yl)piperazine-1-carboxylate 在 四丁基硫酸氢铵 、 magnesium 、 对甲苯磺酰肼 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 5.95h， 生成 tert-butyl 4-(m-tolylsulfonyl)-4,6,6a,7,9,10-hexahydro-8H-pyrazino[1,2-a]pyrrolo[4,3,2-de]quinoline-8-carboxylate
  参考文献：
  名称：

  Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT₆ and Dopamine D₂ Receptor Ligands.

  摘要：

  By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D-2 and serotonin S-HT6 receptor subtype, respectively. While the S-HT6 ligands were antagonists, the D-2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson's disease, and cognitive deficits.

  DOI：

  10.1021/jm5003759
• 作为产物：
  描述：

  4-(1H-4-吲哚)-哌嗪-1-羧酸叔丁酯 在 苄基三乙基氯化铵 、 sodium hydroxide 、 三氯氧磷 作用下， 以 水 、 甲苯 为溶剂， 反应 4.0h， 生成 tert-butyl 4-(3-formyl-1-tosyl-1H-indol-4-yl)piperazine-1-carboxylate
  参考文献：
  名称：

  [EN] NOVEL 4-(ARYL-4-SULFONYL)-6,6a,7,8,9,10-HEXAHYDRO-4H-4,8,10a-TRIAZA-ACEPHENANTHRYLENE AND 3-ARYLSULFONYL-6,6a,7,8,9,10-HEXAHYDRO-3H-3,8,10a-TRIAZA-CYCLOPENTA[C]FLUORENE DERIVATIVES AS SEROTONIN 5-HT6 LIGANDS
  [FR] NOUVEAUX DÉRIVÉS DE 4-(ARYL-4-SULFONYL)-6,6A,7,8,9,10-HEXAHYDRO-4H-4,8,10A-TRIAZA-ACÉPHÉNANTHRYLÈNE ET 3-ARYLSULFONYL-6,6A,7,8,9,10-HEXAHYDRO-3H-3,8,10A-TRIAZA-CYCLOPENTA[C]FLUORÈNE EN TANT QUE LIGANDS DE SÉROTONINE 5-HT6

  摘要：

  本发明涉及式I或II的化合物，它们是血清素5-HT6受体配体。本发明提供了一种药物组合物，其包含本发明的化合物以及药学上可接受的载体的治疗有效量。本发明还提供了制备式I或II的化合物或其药学上可接受的盐的方法。本发明进一步提供了一种治疗患有神经退行性疾病的受试者的方法，包括向该受试者施用式I或II的化合物或其药学上可接受的盐的治疗有效量。本发明还提供了一种治疗患有精神疾病的受试者的方法，包括向该受试者施用式I或II的化合物或其药学上可接受的盐的治疗有效量。

  公开号：

  WO2011088836A1

文献信息

• [EN] NOVEL 4-(ARYL-4-SULFONYL)-6,6a,7,8,9,10-HEXAHYDRO-4H-4,8,10a-TRIAZA-ACEPHENANTHRYLENE AND 3-ARYLSULFONYL-6,6a,7,8,9,10-HEXAHYDRO-3H-3,8,10a-TRIAZA-CYCLOPENTA[C]FLUORENE DERIVATIVES AS SEROTONIN 5-HT6 LIGANDS<br/>[FR] NOUVEAUX DÉRIVÉS DE 4-(ARYL-4-SULFONYL)-6,6A,7,8,9,10-HEXAHYDRO-4H-4,8,10A-TRIAZA-ACÉPHÉNANTHRYLÈNE ET 3-ARYLSULFONYL-6,6A,7,8,9,10-HEXAHYDRO-3H-3,8,10A-TRIAZA-CYCLOPENTA[C]FLUORÈNE EN TANT QUE LIGANDS DE SÉROTONINE 5-HT6
  申请人：LUNDBECK & CO AS H

  公开号：WO2011088836A1

  公开（公告）日：2011-07-28

  This invention is directed to compounds of formula I or II, which are serotonin 5-HT 6 ligands. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. The present invention also provides processes for the preparation of the compounds of formula I or II, or a pharmaceutically acceptable salt thereof. The present invention further provides a method of treating a subject suffering from a neurodegenerative disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I or II, or a pharmaceutically acceptable salt thereof. The present invention further provides a method of treating a subject suffering from a psychiatric disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I or II, or a pharmaceutically acceptable salt thereof.

  本发明涉及式I或II的化合物，它们是血清素5-HT6受体配体。本发明提供了一种药物组合物，其包含本发明的化合物以及药学上可接受的载体的治疗有效量。本发明还提供了制备式I或II的化合物或其药学上可接受的盐的方法。本发明进一步提供了一种治疗患有神经退行性疾病的受试者的方法，包括向该受试者施用式I或II的化合物或其药学上可接受的盐的治疗有效量。本发明还提供了一种治疗患有精神疾病的受试者的方法，包括向该受试者施用式I或II的化合物或其药学上可接受的盐的治疗有效量。
• [EN] NOVEL 6,6A,7,8,9,10-HEXAHYDRO-4H-4,8,10A-TRIAZA-ACEPHENANTHRYLENE DERIVATIVES AS DOPAMINE D2 LIGANDS<br/>[FR] NOUVEAUX DÉRIVÉS 6,6A,7,8,9,10-HEXAHYDRO-4H-4,8,10A-TRIAZA-ACÉPHÉNANTHRYLÈNE EN TANT QUE LIGANDS DES RÉCEPTEURS D2 DE LA DOPAMINE
  申请人：LUNDBECK & CO AS H

  公开号：WO2011088838A1

  公开（公告）日：2011-07-28

  This invention is directed to compounds, which are dopamine D2 ligands. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. The present invention also provides processes for the preparation of the compounds of formula I or formula II, or a pharmaceutically acceptable salt thereof. The present invention further provides a method of treating a subject suffering from a neurodegenerative disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I or formula II, or a pharmaceutically acceptable salt thereof. The present invention further provides a method of treating a subject suffering from a psychiatric disorder comprising administering to the subject a therapeutically effective amount of a compound of formula I or formula II, or a pharmaceutically acceptable salt thereof.

  这项发明涉及多巴胺D2受体配体化合物。该发明提供了一种包括该发明化合物的治疗有效量和药用载体的药物组合物。本发明还提供了制备式I或式II化合物或其药用可接受盐的方法。本发明还提供了一种治疗患有神经退行性疾病的受试者的方法，包括向受试者施用式I或式II化合物或其药用可接受盐的治疗有效量。本发明还提供了一种治疗患有精神障碍的受试者的方法，包括向受试者施用式I或式II化合物或其药用可接受盐的治疗有效量。
• Novel difluoromethylated 1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole derivatives as potent 5-HT6 receptor antagonist with AMDE-improving properties: Design, synthesis, and biological evaluation
  作者：Chao Yi、Kangzhi Chen、Haiping Liang、Zusheng Wang、Tao Wang、Kai Li、Jiahui Yu、Jiexie Sun、Chuanfei Jin

  DOI：10.1016/j.bmc.2022.116950

  日期：2022.10

  Serotonin type 6 receptor (5-HT6R) has been considered as a particularly promising target for treating cognitive deficits due to the positive effects of its antagonists in a wide range of memory impairment paradigms. In this study, we designed, synthesized, and evaluated a series of 3-(difluoromethyl)-1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole derivatives as potent 5-HT6R antagonists. Structure-activity

  6 型血清素受体 (5-HT 6 R) 已被认为是治疗认知缺陷的特别有希望的靶标，因为其拮抗剂在广泛的记忆障碍范式中具有积极作用。在这项研究中，我们设计、合成和评估了一系列 3-(二氟甲基)-1-(苯磺酰基)-4-(哌嗪-1-基)-1 H-吲哚衍生物作为有效的 5-HT 6 R 拮抗剂。构效关系研究导致发现五种化合物（6a、6m、6n、6p和6q ）在 5-HT 6 R处具有强结合亲和力。大鼠体内药代动力学研究，6p通过使用二氟甲基取代甲基，AUC (267 ng·h/mL) 和生物利用度 (34.39 %) 比6a (分别为 9.37 ng·h/mL 和 5.95 %) 高 30 倍。此外，6p表现出良好的脑穿透性，C b /C p比约为 6。基于药理特性和有利的药代动力学特性，进一步选择6p来评估初步体内模型中的认知增强特性。研究发现，6p不仅可以防止东莨菪碱诱导的新物体识别测试中的学
• Syntheses of aza-analogous iso-ergoline scaffolds using carbene mediated C–H insertion
  作者：Niels Krogsgaard-Larsen、Mikael Begtrup、Karla Frydenvang、Jan Kehler

  DOI：10.1016/j.tet.2010.09.023

  日期：2010.11

  A novel direct flexible and robust approach to the iso-ergoline tetracyclic system in which a five or six-membered ring is established by intramolecular carbene C-H insertion is reported The protocol involves a two step conversion of an aromatic aldehyde to the corresponding hydrazone and without purification further conversion to the diazo-compound followed by thermal carbene formation and C-H insertion alpha to a nitrogen (C) 2010 Elsevier Ltd All rights reserved
• Novel Aza-analogous Ergoline Derived Scaffolds as Potent Serotonin 5-HT₆ and Dopamine D₂ Receptor Ligands.
  作者：Niels Krogsgaard-Larsen、Anders A. Jensen、Tenna J. Schrøder、Claus. T. Christoffersen、Jan Kehler

  DOI：10.1021/jm5003759

  日期：2014.7.10

  By introducing distal substituents on a tetracyclic scaffold resembling the ergoline structure, two series of analogues were achieved exhibiting subnanomolar receptor binding affinities for the dopamine D-2 and serotonin S-HT6 receptor subtype, respectively. While the S-HT6 ligands were antagonists, the D-2 ligands displayed intrinsic activities ranging from full agonism to partial agonism with low intrinsic activity. These structures could potentially be interesting for treatment of neurological diseases such as schizophrenia, Parkinson's disease, and cognitive deficits.