5,6,7,8,9,10-hexahydro-7,10-iminocycloheptindole | 147213-03-4

• 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: 5,6,7,8,9,10-hexahydro-7,10-iminocycloheptindole
• 英文别名: 11-methyl-5,6,7,8,9,10-hexahydro-7,10-epiminocyclohepta[b]indole；5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole；9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraene
• CAS: 147213-03-4
• 化学式: C₁₃H₁₄N₂
• 分子量: 198.268
• InChiKey: ZUBTZRPXJLZWKF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  27.8
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  5,6,7,8,9,10-hexahydro-7,10-iminocycloheptindole 在 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成
  参考文献：
  名称：

  Synthesis and in vitro evaluation of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles: high-affinity ligands for the N,N'-di-o-tolylguanidine-labeled .sigma. binding site

  摘要：

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclo[b]indoles substituted at the 5 and/or 11 positions was synthesized from tropinone. Affinity for sigma binding sites was determined using [H-3]-N,N'-di-o-tolylguanidine ([H-3]DTG) and [H-3]-(+)-3-(3-hydroxyphenyl)-N-1-propylpiperidine ([H-3]-(+)-3-PPP) and for the dopamine D2 receptor labeled with [H-3]sulpiride. Nearly all compounds studied in this series possessed a higher affinity for [H-3]DTG than [H-3]-(+)-PPP-labeled sigma sites, suggesting that [H-3]DTG and [H-3]-(+)-3-PPP radioligands label pharmacologically distinct sigma binding sites, as reported previously. Substitution at the 11 position with side chains containing a four-carbon tether resulted in compounds having the highest affinity for the [H-3]DTG-labeled a site. The most potent and selective member of this series was 11-[4-(2-furanyl)butyl]-5,6,7,8,9, 10-hexahydro-7,10-iminocyclohept[b]indole(40). Enantioselectivity was investigated by preparing the (+)- and (-)-isomers of 40. These studies revealed that (+)-40 was more potent at the [H-3]-DTG-labeled sigma site whereas (-)-40 had a higher affinity at sigma sites labeled with [H-3]-(+)-PPP. Racemic 40 was observed to possess a higher affinity than either of its respective enantiomers at both the [H-3]DTG- and [H-3]-(+)-3-PPP-labeled sites, suggesting an allosteric interaction.

  DOI：

  10.1021/jm00055a005
• 作为产物：
  描述：

  tropinone 在 potassium carbonate 、 溶剂黄146 、 锌 作用下， 生成 5,6,7,8,9,10-hexahydro-7,10-iminocycloheptindole
  参考文献：
  名称：

  Bridged .gamma.-carbolines and derivatives possessing selective and combined affinity for 5-HT2 and D2 receptors

  摘要：

  A series of 5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indoles and 6,7,8,9,10,11-hexahydro-7,-11-imino-5H-cyclooct[b]indoles was prepared. Structural modifications of the lead compound, 11-[4-(4-fluorobenzoyl)propyl]-5,6,7,8,9,10-hexahydro-7,10-iminocyclohept[b]indole (5, K(i) = 0.82 nM vs [H-3]ketanserin) enabled the identification of the functionality necessary for high affinity at serotonin 5-HT2 and dopamine D2 receptors in ligand binding studies. The indole ring, as well as the benzoyl or isosteric benzisoxazole moiety, were essential for high affinity. Variations of the length of the side chains resulted in ligands having either selective affinity for the 5-HT2 receptor or a combination of 5-HT2 and D2 affinity. In vivo binding studies were performed on selected members in this series. The most potent member, 2-fluoro-11-[4-(4-fluorobenzoyl)butyl]-5,6,7,8,9,-10-hexahydro-7,10-iminocyclohept[b]indole (36) had an ED50 of <1 mg/kg at the 5-HT2 and D2 receptors following oral administration.

  DOI：

  10.1021/jm00062a023

文献信息

• [EN] 1, 3, 4, 5-TETRAHYDRO-2H-PYRIDO[4,3-B]INDOLE DERIVATIVES FOR THE TREATMENT, ALLEVIATION OR PREVENTION OF DISORDERS ASSOCIATED WITH TAU AGGREGATES LIKE ALZHEIMER'S DISEASE<br/>[FR] DÉRIVÉS DE 1,3,4,5-TÉTRAHYDRO-2H-PYRIDO[4,3-B]INDOLE POUR LE TRAITEMENT, LE SOULAGEMENT OU LA PRÉVENTION DE TROUBLES ASSOCIÉS À DES AGRÉGATS DE TAU COMME LA MALADIE D'ALZHEIMER
  申请人：AC IMMUNE SA

  公开号：WO2019134978A1

  公开（公告）日：2019-07-11

  The present invention relates to novel compounds that can be employed in the treatment, alleviation or prevention of a group of disorders and abnormalities associated with Tau (Tubulin associated unit) protein aggregates including, but not limited to, Neurofibrillary Tangles (NFTs), such as Alzheimer's disease (AD).

  本发明涉及一类新化合物，可用于治疗、缓解或预防与Tau蛋白聚集相关的一组疾病和异常，包括但不限于神经原纤维缠结（NFTs），如阿尔茨海默病（AD）。
• 5,6,7,8,9,10-hexahydro-7
  申请人：Scios Nova Inc.

  公开号：US05250537A1

  公开（公告）日：1993-10-05

  5,6,7,8,9,10-Hexahydro-7,10-iminocyclohept[b]indole, 6,7,8,9,10,11-hexahydro-7,11-imino-5H-cyclooct[b]indole and substituted derivatives are effective in the treatment of psychoses with limited liability to produce concomitant adverse extrapyramidal symptoms. These compounds are also useful for treating other central nervous system and cardiovascular disorders.

  5,6,7,8,9,10-六氢-7,10-亚胺环庚[b]吲哚，6,7,8,9,10,11-六氢-7,11-亚胺-5H-环辛[b]吲哚及其取代衍生物在治疗精神病时具有效性，且对产生并发不良的外周运动障碍症状的风险有限。这些化合物也适用于治疗其他中枢神经系统和心血管疾病。
• [EN] BRIDGED HETEROCYCLIC COMPOUNDS AND METHODS OF USE<br/>[FR] COMPOSÉS HÉTÉROCYCLIQUES PONTÉS ET LEURS MÉTHODES D'UTILISATION
  申请人：MEDIVATION TECHNOLOGIES INC

  公开号：WO2011038164A1

  公开（公告）日：2011-03-31

  This disclosure relates to new compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new bridged heterocyclic [4,3-b]indole compounds. Pharmaceutical compositions are also provided. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

  本披露涉及新化合物，可用于调节个体中的组胺受体。描述了新的化合物，包括新的桥式杂环[4,3-b]吲哚化合物。还提供了制药组合物。提供了包含该化合物的制药组合物，以及使用该化合物进行各种治疗应用的方法，包括治疗认知障碍、精神障碍、神经递质介导的障碍和/或神经元障碍。
• INDOLE AND INDOLINE DERIVATIVES AND METHODS OF USE THEREOF
  申请人：Schrimpf Michael R.

  公开号：US20100087471A1

  公开（公告）日：2010-04-08

  The present application relates to indole and indoline derivatives of formula (I), (II), (III), (IV), (V), or (VI) wherein a, R 1 , R 2 , R 3 , R 4 , R 5 , U, V, W, X, Y, and Z are as defined in the specification. The present application also relates to compositions comprising such compounds, and methods of treating disease conditions using such compounds and compositions, and methods for identifying such compounds.

  本申请涉及公式(I)、(II)、(III)、(IV)、(V)或(VI)的吲哚和吲哚啉衍生物，其中a、R1、R2、R3、R4、R5、U、V、W、X、Y和Z如规范中所定义。本申请还涉及包含这些化合物的组合物，以及使用这些化合物和组合物治疗疾病状况的方法，以及鉴定这些化合物的方法。
• BRIDGED HETEROCYCLIC COMPOUNDS AND METHODS OF USE
  申请人：MEDIVATION TECHNOLOGIES, INC.

  公开号：US20130190303A1

  公开（公告）日：2013-07-25

  This disclosure relates to new compounds that may be used to modulate a histamine receptor in an individual. Novel compounds are described, including new bridged heterocyclic [4,3-b]indole compounds. Pharmaceutical compositions are also provided. Pharmaceutical compositions comprising the compounds are also provided, as are methods of using the compounds in a variety of therapeutic applications, including the treatment of a cognitive disorder, psychotic disorder, neurotransmitter-mediated disorder and/or a neuronal disorder.

  本公开涉及可用于调节组织胺受体的新化合物。其中描述了新的桥接杂环[4,3-b]吲哚化合物。还提供了制药组合物，包括含有该化合物的制药组合物。还提供了使用该化合物进行各种治疗应用的方法，包括治疗认知障碍、精神障碍、神经递质介导的障碍和/或神经元障碍。