3-chloro-1-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-one

• 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: 3-chloro-1-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-one
• 英文别名: 3-chloro-1-(3-chloro-10,11-dihydro-5H-dibenz[b,f]azepin-5-yl)-1-propanone；3-chloro-1-(2-chloro-5,6-dihydrobenzo[b][1]benzazepin-11-yl)propan-1-one
• 化学式: C₁₇H₁₅Cl₂NO
• 分子量: 320.218
• InChiKey: QKDUONNAIUTQRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  3-chloro-1-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-one 在 硼烷四氢呋喃络合物 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 5.5h， 以46%的产率得到3-氯-5-(3-氯丙基)-10,11-二氢-5H-二苯并[b,f]氮杂卓
  参考文献：
  名称：

  Reengineered tricyclic anti-cancer agents

  摘要：

  The phenothiazine and dibenzazepine tricyclics are potent neurotropic drugs with a documented but underutilized anti-cancer side effect. Reengineering these agents (TFP, CPZ, CIP) by replacing the basic amine with a neutral polar functional group (e.g., RTC-1, RTC-2) abrogated their CNS effects as demonstrated by in vitro pharmacological assays and in vivo behavioral models. Further optimization generated several phenothiazines and dibenzazepines with improved anti-cancer potency, exemplified by RTC-5. This new lead demonstrated efficacy against a xenograft model of an EGFR driven cancer without the neurotropic effects exhibited by the parent molecules. Its effects were attributed to concomitant negative regulation of PI3K-AKT and RAS-ERK signaling. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.07.007
• 作为产物：
  描述：

  3-氯亚氨基二苄 、 3-氯丙酰氯 在 sodium hydroxide 作用下， 以 甲苯 为溶剂， 生成 3-chloro-1-(3-chloro-10,11-dihydro-5H-dibenzo[b,f]azepin-5-yl)propan-1-one
  参考文献：
  名称：

  N-substituted azaheterocyclic carboxylic acids and esters thereof

  摘要：

  本发明涉及新型N-取代的氮杂环羧酸及其酯，其中取代烷基链构成N-取代基的一部分或其盐，以及其制备方法、含有它们的组合物，以及它们在临床治疗疼痛、高敏感和/或炎症条件中的应用，其中C-纤维通过引发神经源性疼痛或炎症发挥病理生理作用。

  公开号：

  US06239148B1

文献信息

• [EN] HECT E3 LIGASE INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE LIGASE E3 HECT ET LEURS UTILISATIONS
  申请人：IFOM FONDAZIONE ST FIRC DI ONCOLOGIA MOLECOLARE

  公开号：WO2020245213A1

  公开（公告）日：2020-12-10

  The present invention relates to tricyclic derivatives of formula (I), which are useful as inhibitors of HECT-domain-containing E3 ligases, in particular NEDD4. The present invention also refers to pharmaceutical compositions comprising compounds of formula (I), to their medical use and to their process of preparation.

  本发明涉及公式（I）的三环衍生物，其作为HECT结构域含有E3连接酶的抑制剂，特别是NEDD4。本发明还涉及包含公式（I）化合物的药物组合物，它们的医疗用途以及它们的制备方法。
• N-substituted azaheterocyclic carboxylic acids and esters thereof
  申请人：Novo Nordisk A/S

  公开号：US06239148B1

  公开（公告）日：2001-05-29

  The present invention relates to novel N-substituted azaheterocyclic carboxylic acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.

  本发明涉及新型N-取代的氮杂环羧酸及其酯，其中取代烷基链构成N-取代基的一部分或其盐，以及其制备方法、含有它们的组合物，以及它们在临床治疗疼痛、高敏感和/或炎症条件中的应用，其中C-纤维通过引发神经源性疼痛或炎症发挥病理生理作用。
• 1,4-disubstituted piperazines
  申请人：Novo Nordisk A/S

  公开号：US05916889A1

  公开（公告）日：1999-06-29

  The present invention relates to 1,4-disubstituted piperazines of the general formula ##STR1## wherein X, Y, Z, R.sup.1, R.sup.2 and r are as defined in the detailed part of the present description or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation as well as their use for the treatment of indications caused by or related to the secretion and circulation of insulin antagonizing peptides, e.g. non-insulin-dependent diabetes mellitus (NIDDM) and ageing-associated obesity.

  本发明涉及一般式为##STR1##的1,4-二取代哌嗪，其中X、Y、Z、R.sup.1、R.sup.2和r如本说明书详细部分所定义，或其盐，以及它们的制备方法、含有它们的组合物，以及它们用于临床治疗疼痛、高敏感和/或炎症症状的用途，其中C-纤维通过诱导神经源性疼痛或炎症发挥病理生理作用，以及它们用于治疗由胰岛素拮抗肽的分泌和循环引起或相关的适应症，例如非胰岛素依赖性糖尿病（NIDDM）和与衰老相关的肥胖症。
• Tricyclic compounds in treating hyperalgesic conditions and NIDDM
  申请人：Novo Nordisk A/S

  公开号：US05962449A1

  公开（公告）日：1999-10-05

  The present invention relates to novel N-substituted amino acids and esters thereof in which a substituted alkyl chain forms part of the N-substituent or salts thereof, to methods for their preparation, to compositions containing them, and to their use for the clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammation.

  本发明涉及新颖的N-取代氨基酸及其酯，其中取代的烷基链形成N-取代基的一部分或其盐，以及它们的制备方法、含有它们的组合物，以及它们在临床治疗疼痛、过敏性疼痛和/或炎症情况中的用途，其中C-纤维通过引发神经源性疼痛或炎症发挥病理生理作用。
• N-substituted azaheterocyclic carboxylic acids and their use
  申请人：Novo Nordisk A/S

  公开号：US06613791B1

  公开（公告）日：2003-09-02

  N-substituted azaheterocycyclic carboxylic acids and esters thereof of the formula I wherein Z, X, R1, R2 and r are defined in the specification. Compositions thereof and methods for preparing the compounds are disclosed. The compounds are useful for clinical treatment of painful, hyperalgesic and/or inflammatory conditions in which C-fibers play a pathophysiological role by eliciting neurogenic pain or inflammations.

  本发明公开了式I中Z、X、R1、R2和r在说明书中定义的N-取代的杂环羧酸及其酯类。公开了这些化合物的组成及其制备方法。这些化合物在临床治疗C纤维通过引起神经源性疼痛或炎症所起的病理生理作用的疼痛、高敏感和/或炎症病症中非常有用。