7,8-dimethoxy-1-(o-tolyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine | 1186236-32-7

• 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: 7,8-dimethoxy-1-(o-tolyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine
• CAS: 1186236-32-7
• 化学式: C₁₉H₂₃NO₂
• 分子量: 297.397
• InChiKey: YHSJQRWFDBYPBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  22.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  30.49
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  7,8-dimethoxy-1-(o-tolyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine 、 三聚乙醛 在 盐酸 、 溴 、 溶剂黄146 、 甲酸 作用下， 以 水 为溶剂， 以51.5%的产率得到6-bromo-7,8-dimethoxy-3-methyl-1-m-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine
  参考文献：
  名称：

  Synthesis of 6-substituted 1-phenylbenzazepines and their dopamine D1 receptor activities

  摘要：

  A series of racemic 6-aryl substituted 1-phenylbenzazepines 7a-e, and 17a,b were prepared. All these compounds showed binding potencies compatible to or much higher than that of the prototypic (+/-)-SKF- 38393 ((+/-)-1) and (+/-)-SKF-83959 (3) for the D(1) receptor. Among analogs of (+/-)-SKF-38393, compounds 7b, 7c and 7e possess 10-, 2- and 7-fold enhancement in binding for the D(1) receptor, respectively. Lower but compatible potency to that of (+/-)-1 was observed for compounds 7a and 7d. The optimal 6-substituents (m-tolyl, and 2 '-naphthyl) were applied to the skeleton of (+/-)-SKF-83959 (3). The resulting compounds 17a, b displayed high affinity at the D(1) receptor, only slightly lower than that of (3). These two compounds also showed good binding at the D(2) receptor. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.049

文献信息

• Unprecedented FeCl₃⋅6 H₂O-Promoted Skeleton Rearrangement of 1-Aryl-2,3,4,5-tetrahydro-1<i>H</i>-3-benzazepines: A New Strategy for the Synthesis of C1 Quaternary Tetrahydroisoquinolines
  作者：Jing Zhang、Ao Zhang

  DOI：10.1002/chem.200901197

  日期：2009.10.26

  Substituent matters: A skeleton rearrangement of 1‐aryl‐3‐benzazepines was developed with 2.0 equiv of FeCl3⋅6 H2O in PhNO2. The N‐substituents had a dramatic influence on the structures of the products. In the case of N‐alkylbenzazepines, 1‐aryltetrahydroisoquinolines were obtained, whereas N‐acyl‐benzazepines yielded a series of unique C1 quaternary 1‐aryl‐1‐formyltetrahydroisoquinolines.

  取代基事项：A骨架的1-芳基-3-苯并吖庚因的重排用的FeCl的2.0当量开发3 ⋅6ħ 2 ö在PHNO 2。该ñ -取代了对产品结构的显着影响。在N-烷基苯并ze庚因的情况下，获得了1-芳基四氢异喹啉，而N-酰基-苯并ze庚因产生了一系列独特的C1季铵基1-芳基-1-甲酰基四氢异喹啉。
• ‘Click’ D1 receptor agonists with a 5-HT1A receptor pharmacophore producing D2 receptor activity
  作者：Jing Zhang、Hai Zhang、Wenxian Cai、Leiping Yu、Xuechu Zhen、Ao Zhang

  DOI：10.1016/j.bmc.2009.06.019

  日期：2009.7

  A series of new 1-aryl-3-benzazepine derivatives containing an arylpiperazinyl function as the N3 substituent were synthesized by combining a D-1 receptor agonistic pharmacophore and a 5-HT1A receptor pharmacophore through Click reaction. Interestingly, these compounds generally do not have good binding affinity at the D-1 receptor, but most compounds are potent at both D-2 and 5-HT1A receptors. Compound 8h, containing 1-m-tolyl-benzazepine scaffold and 2-methoxyphenylpiperazine core, displayed good affinity at all tested receptors, with K-i values of 144, 80, and 133 nM, for the D-1, D-2, and 5-HT1A receptors, respectively. Compound 13 with the triazole moiety formed differently from that in 8h showed the highest affinity at the D-2 receptor with K-i value of 19 nM. This compound also showed moderate affinity at the 5-HT1A (K-i, 105 nM), and D-1 (K-i, 551 nM) receptors. Functional assays indicated that both compounds 13 and 8h are antagonists at D-1 and D-2 receptors, whereas full agonistic activity at the 5-HT1A receptor was observed. In agreement with the binding affinity, compound 13 is a high efficacy D-2 antagonist and 5-HT1A agonist. (C) 2009 Elsevier Ltd. All rights reserved.