9-Methyl-9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraene | 149381-98-6

• 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: 9-Methyl-9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraene
• CAS: 149381-98-6
• 化学式: C₁₄H₁₆N₂
• 分子量: 212.294
• InChiKey: XNRBTWJSSWCPRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  17
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  9-Methyl-9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraene 、 alkaline earth salt of/the/ methylsulfuric acid 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以72%的产率得到1-(4-Fluorophenyl)-4-(9-methyl-9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraen-15-yl)butan-1-one
  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
• 作为产物：
  描述：

  (1R,5S)-3-Oxo-8-aza-bicyclo[3.2.1]octane-8-carboxylic acid 2,2,2-trichloro-ethyl ester 在 溶剂黄146 、 锌 作用下， 生成 9-Methyl-9,15-diazatetracyclo[10.2.1.02,10.03,8]pentadeca-2(10),3,5,7-tetraene
  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] 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。
• BRIDGED HETEROCYCLIC COMPOUNDS AND METHODS OF USE
  申请人：Medivation Technologies, Inc.

  公开号：EP2480081A1

  公开（公告）日：2012-08-01
• Bridged .gamma.-carbolines and derivatives possessing selective and combined affinity for 5-HT2 and D2 receptors
  作者：Richard E. Mewshaw、Lisa S. Silverman、Rose M. Mathew、Carl Kaiser、Ronald G. Sherrill、Menyan Cheng、Carol W. Tiffany、E. William Karbon、Michael A. Bailey

  DOI：10.1021/jm00062a023

  日期：1993.5

  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.