7,8-dimethoxy-1-(4-nitrophenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine | 754946-42-4

• 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-(4-nitrophenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine
• 英文别名: 7,8-dimethoxy-1-(4'-nitrophenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine；7,8-dimethoxy-5-(4-nitrophenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine
• CAS: 754946-42-4
• 化学式: C₁₈H₂₀N₂O₄
• 分子量: 328.368
• InChiKey: QBJMSFHISYGYQB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.89
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  73.63
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  7,8-dimethoxy-1-(4-nitrophenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 乙醇 为溶剂， 反应 72.0h， 生成 7,8-dihydroxy-1-(4'-aminophenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride
  参考文献：
  名称：

  Fluorescent probes for dopamine receptors: synthesis and characterization of fluorescein and 7-nitrobenz-2-oxa-1,3-diazol-4-yl conjugates of D-1 and D-2 receptor ligands

  摘要：

  Fluorescent probes have been designed and developed for dopamine D-1 and D-2 receptors. Fluorescein and/or NBD (7-nitrobenz-2-oxa-1,3-diazol-4-yl) derivatives of PPHT (D-2 agonist), spiperone (D-2 antagonist), SKF 38393 (D-1 agonist), and SKF 83566 (D-1 antagonist) were synthesized via their amino-functionalized analogues and all ligands were pharmacologically evaluated by measuring their ability to displace [H-3]SCH 23390 and [H-3]spiperone from D-1 and D-2 receptor sites in caudate putamen of monkeys (Macaca fascicularis). The fluorescein derivatives of PPHT and SKF 83566 and the NBD derivatives of spiperone and SKF 83566 retained the high affinity and selectivity of the parent ligands. The NBD derivatives of PPHT showed higher D-2 receptor affinity and selectivity than their parent ligands. The enantiomers of the fluorescent derivatives of PPHT were also synthesized and were found to exhibit stereoselectivity in binding to the D-2 receptor, with the S enantiomers having a considerably higher affinity than their R analogues. In contrast to these results, the fluorescein derivative of SKF 38393 showed only a low affinity for the D-1 receptor. These fluorescein- and NBD-coupled D-1 and D-2 receptor ligands have considerable significance as potential probes in the study of distribution of the receptors at the cellular/subcellular level and of their mobility in membranes in normal/diseased states by use of fluorescence microscopic and fluorescence photobleaching recovery techniques, respectively. The development of these novel fluorescent probes should also provide new leads for the design and synthesis of additional fluorescent ligands with better fluorescent properties and/or higher affinity/selectivity for the DA receptors.

  DOI：

  10.1021/jm00115a012
• 作为产物：
  描述：

  (P-硝基苯基)环氧乙烷 在 PPA 作用下， 以 四氢呋喃 为溶剂， 反应 1.5h， 生成 7,8-dimethoxy-1-(4-nitrophenyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine
  参考文献：
  名称：

  Design, synthesis and biological evaluation of bivalent ligands against A1–D1 receptor heteromers

  摘要：

  设计并合成腺苷A1-多巴胺D1受体异聚体(A1-D1R)的双价配体，并评估其药理活性。设计并合成了双价配体及其相应的A1R单价配体。使用放射性标记的结合试验，检测了双价配体在大鼠脑膜制备物中对A1R和D1R的亲和力。为了证明A1-D1R的形成，在转染了D1-CFP和A1-YFP的HEK293细胞中进行了荧光共振能量转移(FRET)。使用分子建模分析了可能的蛋白质-蛋白质和蛋白质-配体相互作用模式。合成了两种A1R和D1R的双价配体(20a, 20b)及其相应的A1R单价配体(21a, 21b)。在放射性标记的结合试验中，双价配体对A1R的亲和力比相应的单价配体高出10-100倍。在FRET实验中，与相应的单价配体相比，双价配体显著增加了A1R和D1R的异源二聚化。通过分子建模建立了一个异源二聚体模型，该模型在A1R的螺旋3、4、5和D1R的螺旋1、6、7之间有界面。在异源二聚体模型中，两个配体结合位点之间的距离约为48.4 Å，比双价配体的长度短。这项研究证明了A1-D1R在体内的存在以及双价配体与两个受体的同时相互作用。

  DOI：

  10.1038/aps.2012.151