1-(苯基磺酰基)-4-(1-哌嗪)-1H-吲哚 | 412049-71-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 1-(苯基磺酰基)-4-(1-哌嗪)-1H-吲哚
• 英文名称: 1-(phenylsulfonyl)-4-(piperazin-1-yl)-1H-indole
• 英文别名: 1-(phenylsulfonyl)-4-(1-piperazinyl)-1H-indole；1-(benzenesulfonyl)-4-piperazin-1-ylindole
• CAS: 412049-71-9
• 化学式: C₁₈H₁₉N₃O₂S
• 分子量: 341.434
• InChiKey: OPAMDWUUNKYGOR-UHFFFAOYSA-N

物化性质

• 沸点：
  579.2±53.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  62.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(苯基磺酰基)-4-(1-哌嗪)-1H-吲哚 在 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 23.0h， 生成 (S)-2-((4-(4-(4-(1-(phenylsulfonyl)-1H-indol-4-yl)piperazin-1-yl)butoxy)benzyl)amino)propanamide
  参考文献：
  名称：

  A dual-acting 5-HT6 receptor inverse agonist/MAO-B inhibitor displays glioprotective and pro-cognitive properties

  摘要：

  The complex etiology of Alzheimer's disease has initiated a quest for multi-target ligands to address the multifactorial causes of this neurodegenerative disorder. In this context, we designed dual-acting 5-HT6 receptor (5-HT6R) antagonists/MAO-B inhibitors using pharmacophore hybridization strategy. Our approach involved linking priviliged scaffolds of 5-HT6R with aryloxy fragments derived from reversible and irreversible MAO-B inhibitors. The study identified compound 48 that acts as an inverse agonist of 5-HT6R at Gs signaling and an irreversible MAO-B inhibitor. Compound 48 showed moderate metabolic stability in rat microsomal assay, artificial membrane permeability, no hepatotoxicity, and it was well distributed to the brain. Additionally, 48 showed glioprotective properties in a model of cultured astrocytes using 6-OHDA as the cytotoxic agent. Finally, compound 48 (MED = 1 mg/kg, p.o.) fully reversed memory deficits in the NOR task induced by scopolamine in rats. A better understanding of effects exerted by dual-acting 5-HT6R/MAO-B modulators may impact the future development of neurodegenerative-directed treatment strategies.

  DOI：

  10.1016/j.ejmech.2020.112765
• 作为产物：
  描述：

  4-(1H-4-吲哚)-哌嗪-1-羧酸叔丁酯 在 potassium tert-butylate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 23.0h， 生成 1-(苯基磺酰基)-4-(1-哌嗪)-1H-吲哚
  参考文献：
  名称：

  双环杂芳基哌嗪作为选择性脑渗透剂5-HT6受体拮抗剂。

  摘要：

  从有效且选择性强但对脑渗透性差的5-HT6受体拮抗剂SB-271046开始，采用了一种成功的提高脑部渗透性的策略，该方法涉及构象约束并伴随着氢键数的减少。这提供了一系列具有高5-HT 6受体亲和力的双环杂芳基哌嗪。5-氯吲哚699929结合了高5-HT6受体亲和力和出色的脑渗透性，并且在大鼠和狗中都具有良好的口服生物利用度。

  DOI：

  10.1016/j.bmcl.2005.06.107

文献信息

• 1-Aryl- or 1-alkylsulfonyl-heterocyclylbenzazoles as 5-hydroxytryptamine-6 ligands
  申请人：Wyeth

  公开号：US20040192749A1

  公开（公告）日：2004-09-30

  The present invention provides a compound of formula I and the use thereof in the therapeutic treatment of disorders related to or affected by the 5-HT6 receptor. 1

  本发明提供了一种I式化合物及其在治疗与5-HT6受体相关或受其影响的疾病中的应用。
• 4-piperazinylindole derivatives with 5-HT6 receptor affinity
  申请人：——

  公开号：US20030045527A1

  公开（公告）日：2003-03-06

  This invention relates to compounds which have generally 5-HT6 receptor affinity and which are represented by Formula I: 1 wherein R 3 is SO 2 —Ar, Ar is aryl or heteroaryl; and R 1 , R 2 , R 4 and R 5 are as defined herein; or individual isomers, racemic or non-racemic mixtures of isomers, or pharmaceutically acceptable salts or solvates thereof. The invention further relates to pharmaceutical compositions containing such compounds, methods for their use as therapeutic agents, and methods of preparation thereof.

  这项发明涉及一类通常具有5-HT6受体亲和力的化合物，其由以下式I表示： 其中R3为SO2—Ar，Ar为芳基或杂环芳基；R1、R2、R4和R5如本文所定义；或其各个异构体、外消旋或非外消旋异构体混合物，或其药用可接受盐或溶剂化合物。该发明还涉及含有这类化合物的药物组合物，以及它们作为治疗剂的使用方法和其制备方法。
• Novel compounds, their use and preparation
  申请人：——

  公开号：US20020165251A1

  公开（公告）日：2002-11-07

  The invention provides 2, 3-, 4- or 5-substituted-N1-(arylsulfonyl)indole and (heteroaryl)indole compounds of the general formula (I): 1 in which Ar, R 2 , R 3 , R 4 and R 5 are as defined in the specification. The compounds bind to the 5-HT 6 receptor and are useful for the treatment and prophylaxis of disorders mediated by the 5-HT 6 receptor, such as obesity and CNS disorders.

  这项发明提供了一般式(I)中的2,3-,4-或5-取代-N1-(芳基磺酰基)吲哚和(杂环基)吲哚化合物： 其中Ar，R2，R3，R4和R5如规范中定义。这些化合物与5-HT6受体结合，并可用于治疗和预防由5-HT6受体介导的疾病，如肥胖和中枢神经系统疾病。
• [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。
• Pharmaceutical combination formulation and method of treatment with the combination
  申请人：——

  公开号：US20020068732A1

  公开（公告）日：2002-06-06

  The invention relates to method of preventing or treating a disease related to the 5-HT 2C receptor and the 5-HT 6 receptor, comprising administering to a human or animal subject in need thereof a 5-HT 2C receptor agonist and a 5-HT 6 receptor antagonist in sufficient amounts to provide a therapeutic effect. The invention also relates to a pharmaceutical composition comprising an effective amount of a combination of a 5-HT 2C receptor agonist and a 5-HT 6 receptor antagonist, and optionally a pharmaceutically acceptable carrier.

  该发明涉及一种预防或治疗与5-HT2C受体和5-HT6受体相关的疾病的方法，包括向需要的人类或动物主体施用足够剂量的5-HT2C受体激动剂和5-HT6受体拮抗剂以提供治疗效果。该发明还涉及一种药物组合物，包括有效量的5-HT2C受体激动剂和5-HT6受体拮抗剂的组合物，以及可选择的药用载体。