1,1-dimethylethyl-7-{(3E)-3-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)hydrazono]butanoyl}-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate | 950783-74-1

• 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: 1,1-dimethylethyl-7-{(3E)-3-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)hydrazono]butanoyl}-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate
• 英文别名: tert-butyl 7-[(3E)-3-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]hydrazinylidene]butanoyl]-1,2,4,5-tetrahydro-3-benzazepine-3-carboxylate
• CAS: 950783-74-1
• 化学式: C₂₅H₃₇N₃O₅
• 分子量: 459.586
• InChiKey: NSHTTZXIJBWANO-YZSQISJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  88.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl-7-{(3E)-3-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)hydrazono]butanoyl}-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 7-(1,3-dimethyl-1H-pyrazol-5-yl)-2,3,4,5-tetrahydro-1H-3-benzazepine
  参考文献：
  名称：

  1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists

  摘要：

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.

  DOI：

  10.1021/jm0705612
• 作为产物：
  描述：

  3-(1,1-dimethylethyl)-7-methyl-1,2,4,5-tetrahydro-3H-3-benzazepine-3,7-dicarboxylate 、 1,1-dimethylethyl 1-methyl-2-(1-methylethylidene)hydrazinecarboxylate 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以12 g的产率得到1,1-dimethylethyl-7-{(3E)-3-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)hydrazono]butanoyl}-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate
  参考文献：
  名称：

  1,2,4-Triazol-3-yl-thiopropyl-tetrahydrobenzazepines:  A Series of Potent and Selective Dopamine D₃ Receptor Antagonists

  摘要：

  The discovery of new highly potent and selective dopamine D-3 receptor antagonists has recently permitted characterization of the role of the dopamine D-3 receptor in a wide range, of preclinical animal models. A novel series of 1,2,4-triazol-3-yl-thiopropyl-tetrahydrobenzazepines demonstrating a high level of D3 affinity and selectivity with an excellent pharmacokinetic profile is reported here. In particular, the pyrazolyl derivative 35 showed good oral bioavailability and brain penetration associated with high potency and selectivity in vitro. In vivo characterization of 35 confirmed that this compound blocks the expression of nicotine- and cocaine-conditioned place preference in the rat, prevents nicotine-triggered reinstatement of nicotine- seeking behavior in the rat, reduces oral operant alcohol self- administration in the mouse, increases extracellular levels of acetylcholine in the rat medial prefrontal cortex, and potentiates the amplitude of the relative cerebral blood volume response to d-amphetamine in a regionally specific manner in the rat brain.

  DOI：

  10.1021/jm0705612

文献信息

• Tetrahydrobenzazepine Derivatives as Modulators of Dopamine D3 Receptors (Antipsychotic Agents)
  申请人：Arista Luca

  公开号：US20080139532A1

  公开（公告）日：2008-06-12

  The present invention relates to novel compounds of formula (I) or a pharmaceutically acceptable salt thereof, processes for their preparation, intermediates used in these processes, pharmaceutical compositions containing them and their use in therapy, as modulators of dopamine D 3 receptors, e.g. as agents to treat various aspects drug dependency or as antipsychotic agents.

  本发明涉及公式(I)的新化合物或其药学上可接受的盐，其制备方法，用于这些制备的中间体，含有它们的制药组合物以及它们作为多巴胺D3受体调节剂的治疗用途，例如作为治疗各种药物依赖或作为抗精神病药物的药物。
• 7-Pyrazolylbenzazepines Having Affinity For D3 Receptor
  申请人：Hamprecht Dieter

  公开号：US20080312213A1

  公开（公告）日：2008-12-18

  Compounds of formula (I) or a salt thereof are disclosed: wherein R 1 is pyrazolyl substituted by two or three substituents independently selected from halogen, C 1-4 alkyl and haloC 1-4 alkyl; R 2 is hydrogen or methyl; and R 3 is quinolinyl, oxazolyl or phenyl, each of which is optionally substituted by one or two halogen, C 1-4 alkyl or haloC 1-4 alkyl. Processes for preparation and uses of the compounds in medicine, for example for the treatment of schizophrenia or drug dependency, are also disclosed.

  公开了化合物公式（I）或其盐：其中，R1是吡唑基，其被两个或三个独立选择的取代基取代，所述取代基选择自卤素、C1-4烷基和卤代C1-4烷基；R2是氢或甲基；R3是喹啉基、噁唑基或苯基，每个基都可以被一个或两个卤素、C1-4烷基或卤代C1-4烷基取代。还公开了制备该化合物的方法以及在医学上使用该化合物的用途，例如用于治疗精神分裂症或药物依赖症。
• US8003638B2
  申请人：——

  公开号：US8003638B2

  公开（公告）日：2011-08-23