3-(3-(4-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-1,2,3-triazol-1-yl)propyl)-1-O-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine-7,8-diol | 1186236-55-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 3-(3-(4-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-1,2,3-triazol-1-yl)propyl)-1-O-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine-7,8-diol
• 英文别名: 3-[3-[4-[3-[4-(2-Methoxyphenyl)piperazin-1-yl]propyl]triazol-1-yl]propyl]-5-(2-methylphenyl)-1,2,4,5-tetrahydro-3-benzazepine-7,8-diol
• CAS: 1186236-55-4
• 化学式: C₃₆H₄₆N₆O₃
• 分子量: 610.8
• InChiKey: ACWOUFNDQFUXQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  45
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  90.1
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7,8-dimethoxy-3-(3-(4-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-1,2,3-triazol-1-yl)propyl)-1-o-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine 在 三溴化硼 、 甲醇 作用下， 以 二氯甲烷 为溶剂， 以36%的产率得到3-(3-(4-(3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl)-1H-1,2,3-triazol-1-yl)propyl)-1-O-tolyl-2,3,4,5-tetrahydro-1H-benzo[d]azepine-7,8-diol
  参考文献：
  名称：

  ‘Click’ D1 receptor agonists with a 5-HT1A receptor pharmacophore producing D2 receptor activity

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2009.06.019

文献信息

• ‘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.