(11R,16S)-10,14-diazatetracyclo[8.6.1.05,17.011,16]heptadeca-1,3,5(17)-triene | 313668-95-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: (11R,16S)-10,14-diazatetracyclo[8.6.1.05,17.011,16]heptadeca-1,3,5(17)-triene
• CAS: 313668-95-0
• 化学式: C₁₅H₂₀N₂
• 分子量: 228.337
• InChiKey: DPRWLTPMPVJESF-ZIAGYGMSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  17
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  15.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(2'-aminophenyl)-4-chlorobutan-1-one 、 (11R,16S)-10,14-diazatetracyclo[8.6.1.05,17.011,16]heptadeca-1,3,5(17)-triene 在 potassium carbonate 、 potassium iodide 作用下， 以 1,4-二氧六环 为溶剂， 生成 1-(2-aminophenyl)-4-[(11R,16S)-10,14-diazatetracyclo[8.6.1.05,17.011,16]heptadeca-1,3,5(17)-trien-14-yl]butan-1-one
  参考文献：
  名称：

  Novel, highly potent, selective 5-HT2A/D2 receptor antagonists as potential atypical antipsychotics

  摘要：

  The discover of N-substituted-pyridoindolines and their binding affinities at the 5-HT2A, 5-HT2C and D-2 receptors, and in vivo efficacy as 5-HT2A antagonists is described. The structure-activity relationship of a series of core tetracyclic derivatives with varying butyrophenone sidechains is also discussed. This study has led to the identification of potent, orally bioavailable 5-HT2A/D2 receptor dual antagonists as potential atypical antipsychotics. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)01028-4
• 作为产物：
  描述：

  1-amino-2,3,4,5-tetrahydro-1-benzazepine 在 sodium hydroxide 、 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 异丙醇 为溶剂， 生成 (11R,16S)-10,14-diazatetracyclo[8.6.1.05,17.011,16]heptadeca-1,3,5(17)-triene
  参考文献：
  名称：

  Novel, highly potent, selective 5-HT2A/D2 receptor antagonists as potential atypical antipsychotics

  摘要：

  The discover of N-substituted-pyridoindolines and their binding affinities at the 5-HT2A, 5-HT2C and D-2 receptors, and in vivo efficacy as 5-HT2A antagonists is described. The structure-activity relationship of a series of core tetracyclic derivatives with varying butyrophenone sidechains is also discussed. This study has led to the identification of potent, orally bioavailable 5-HT2A/D2 receptor dual antagonists as potential atypical antipsychotics. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)01028-4

文献信息

• Discovery of a Tetracyclic Quinoxaline Derivative as a Potent and Orally Active Multifunctional Drug Candidate for the Treatment of Neuropsychiatric and Neurological Disorders
  作者：Peng Li、Qiang Zhang、Albert J. Robichaud、Taekyu Lee、John Tomesch、Wei Yao、J. David Beard、Gretchen L. Snyder、Hongwen Zhu、Youyi Peng、Joseph P. Hendrick、Kimberly E. Vanover、Robert E. Davis、Sharon Mates、Lawrence P. Wennogle

  DOI：10.1021/jm401958n

  日期：2014.3.27

  We report the synthesis and structure–activity relationships of a class of tetracyclic butyrophenones that exhibit potent binding affinities to serotonin 5-HT2A and dopamine D2 receptors. This work has led to the discovery of 4-((6bR,10aS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H-pyrido[3′,4′:4,5]pyrrolo[1,2,3-de]quinoxalin-8-yl)-1-(4-fluorophenyl)-butan-1-one 4-methylbenzenesulfonate (ITI-007), which

  我们报告了一类四环丁苯酮的合成与结构-活性关系，这些四环丁酮显示了对5-羟色胺5-HT 2A和多巴胺D 2受体的强结合亲和力。这项工作导致了4-（（6b R，10a S）-3-methyl-2,3,6b，9,10,10 a -hexahydro -1 H，7 H -pyrido [3'，4 ′：4,5]吡咯并[1,2,3- de ]喹喔啉-8-基）-1-（4-氟苯基）-丁-1-酮4-甲基苯磺酸盐（ITI-007），其有效值为5 -HT 2A拮抗剂，突触后D 2素和5-羟色胺转运蛋白的抑制剂。该多功能候选药物具有口服生物利用度，并且在体内表现出良好的抗精神病功效。目前，这种正在研究中的新药正在临床开发中，用于治疗神经精神疾病和神经疾病。
• Substituted heterocycle fused gamma-carbolines
  申请人：——

  公开号：US20040209864A1

  公开（公告）日：2004-10-21

  The present invention is directed to methods of treating addictive behavior and sleep disorders by administering compounds represented by structural Formula (I) 1 or pharmaceutically acceptable salt forms thereof, wherein R 1 , R 5 , R 6a , R 6b , R 7 , R 8 , R 9 , X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.

  本发明涉及通过给予由结构式（I）1所代表的化合物或其药学上可接受的盐形式来治疗成瘾行为和睡眠障碍的方法，其中R1、R5、R6a、R6b、R7、R8、R9、X、b、k、m和n以及虚线在此处描述。本发明治疗方法中使用的化合物是5-羟色胺激动剂和拮抗剂，对于控制或预防包括成瘾行为和睡眠障碍在内的中枢神经系统紊乱是有用的。
• Substituted heterocyle fused gamma-carbolines
  申请人：Robichaud J. Albert

  公开号：US20060178362A1

  公开（公告）日：2006-08-10

  The present invention is directed to compounds useful for treating addictive behavior and sleep disorders represented by structural Formula (I) or pharmaceutically acceptable salt forms thereof, wherein R 1 , R 5 , R 6a , R 6b , R 7 , R 8 , R 9 , X, b, k, m, and n, and the dashed lines are described herein. The compounds used in the method of treatment of this invention are serotonin agonists and antagonists and are useful in the control or prevention of central nervous system disorders including addictive behavior and sleep disorders.

  本发明涉及用于治疗成瘾行为和睡眠障碍的化合物，其结构式表示为(I)，或其药学上可接受的盐形式，其中R1、R5、R6a、R6b、R7、R8、R9、X、b、k、m和n以及虚线如本文所述。本发明方法中使用的化合物是5-羟色胺激动剂和拮抗剂，并且对于控制或预防包括成瘾行为和睡眠障碍在内的中枢神经系统疾病是有用的。
• SUBSTITUTED HETEROCYCLE FUSED GAMMA-CARBOLINES
  申请人：Bristol-Myers Squibb Pharma Company

  公开号：EP1189905B1

  公开（公告）日：2004-09-29
• US6548493B1
  申请人：——

  公开号：US6548493B1

  公开（公告）日：2003-04-15