8-chloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2,5-dione | 87379-41-7

• 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: 8-chloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2,5-dione
• 英文别名: 8-chloro-3,4-dihydro-1H-1-benzazepine-2,5-dione；8-chloro-3,4-dihydro-1H-benzo[b]azepine-2,5-dione
• CAS: 87379-41-7
• 化学式: C₁₀H₈ClNO₂
• 分子量: 209.632
• InChiKey: BUYMLVMIVKWJSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  46.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-chloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2,5-dione 在 sodium ethanolate 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 3.33h， 生成 9-chloro-2-(methylsulfonyl)-5H-benzo[b]pyrimido[4,5-d]azepin-6(7H)-one
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)

  摘要：

  This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

  DOI：

  10.1021/jm2011172
• 作为产物：
  描述：

  8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester 在 水 、 盐酸 作用下， 以 二甲基亚砜 、 水 为溶剂， 生成 8-chloro-1,3,4,5-tetrahydro-2H-1-benzazepin-2,5-dione
  参考文献：
  名称：

  Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)

  摘要：

  This article describes the discovery of a series of potent inhibitors of Polo-like kinase 1 (PLK1). Optimization of this benzolactam-derived chemical series produced an orally bioavailable inhibitor of PLK1 (12c, MLN0905). In vivo pharmacokinetic-pharmacodynamic experiments demonstrated prolonged mitotic arrest after oral administration of 12c to tumor bearing nude mice. A subsequent efficacy study in nude mice achieved tumor growth inhibition or regression in a human colon tumor (HT29) xenograft model.

  DOI：

  10.1021/jm2011172

文献信息

• [EN] 5, 7-DIHYDRO- 6H-PYRIMIDO [ 5, 4-D] [ 1 ] BENZAZEPIN-6-THIONES AS PLK INHIBITORS<br/>[FR] 5, 7-DIHYDRO- 6H-PYRIMIDO [ 5, 4-D] [ 1 ] BENZAZÉPIN-6-THIONES UTILISÉES EN TANT QU'INHIBITEURS DE PLK
  申请人：MILLENNIUM PHARM INC

  公开号：WO2010065134A1

  公开（公告）日：2010-06-10

  This invention provides compounds of formula I: wherein R1, R2, R3, R4, R5, and R6 are as described in the specification. The compounds are inhibitors of PLK and are thus useful for treating proliferative, inflammatory, or cardiovascular disorders.

  本发明提供了公式I的化合物：其中R1、R2、R3、R4、R5和R6如说明书所述。这些化合物是PLK的抑制剂，因此可用于治疗增殖性、炎症性或心血管疾病。
• Synthesis of 7-phenylpyrimido[5,4-<i>d</i>][1]benzazepin-2-ones
  作者：Wen-Yean Chen、Norman W. Gilman

  DOI：10.1002/jhet.5570200330

  日期：1983.5

  The syntheses of the 7-phenylpyrimido[5,4-d][1]benzazepin-2-ones 3, 4, and 5 are described. The 7-phenyl group was introduced by phenylation of the lactam nitrogen in 10, 13 and 16 respectively. One of these compounds, 5, showed moderate activity as a CNS agent.

  描述了7-苯基嘧啶基[5,4- d ] [1]苯并ze庚因-2-酮3、4和5的合成。7-苯基是由内酰胺氮的苯基化在引入10，13和16分别。这些化合物5中的一种显示出适中的CNS活性。
• 5-Substituted 3-chlorokenpaullone derivatives are potent inhibitors of Trypanosoma brucei bloodstream forms
  作者：Oliver C.F. Orban、Ricarda S. Korn、Diego Benítez、Andrea Medeiros、Lutz Preu、Nadège Loaëc、Laurent Meijer、Oliver Koch、Marcelo A. Comini、Conrad Kunick

  DOI：10.1016/j.bmc.2016.06.023

  日期：2016.8

  animals. Inspired by the observation that N(5)-substituted paullones inhibit the trypanothione synthetase from the related parasite Leishmania infantum, we designed and synthesized a series of new derivatives. Although none of the new compounds displayed strong inhibition of Trypanosoma brucei trypanothione synthetase, several of them caused a remarkable growth inhibition of cultivated Trypanosoma brucei

  锥虫硫醇合成酶是动素体寄生虫的必不可少的酶，它会在人类和动物中导致高度致残和致命的疾病。受到N（5）取代的paullones抑制来自相关寄生虫婴儿利什曼原虫的锥虫硫醇合成酶的观察的启发，我们设计并合成了一系列新的衍生物。尽管这些新化合物均未显示出对布鲁氏锥虫Trypanothione合成酶的强抑制作用，但其中有几种化合物对培养的布鲁氏锥虫血流形式产生了显着的生长抑制作用。最强大的同类产品3a 在鼠类巨噬细胞中显示出两位数纳摩尔浓度的抗锥虫活性和三个数量级的选择性指数。
• Lactam compounds useful as protein kinase inhibitors
  申请人：Blackburn Christopher

  公开号：US20060100194A1

  公开（公告）日：2006-05-11

  The present invention provides novel compounds useful as inhibitors of protein kinases. The invention also provides pharmaceutical compositions comprising the compounds of the invention and methods of using the compositions in the treatment of various diseases.

  本发明提供了一种新型化合物，可用作蛋白激酶抑制剂。本发明还提供了包含本发明化合物的制药组合物以及使用该组合物治疗各种疾病的方法。
• Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor
  申请人：Oka Takahiro

  公开号：US20070049593A1

  公开（公告）日：2007-03-01

  The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

  本发明涉及一种四环融合杂环化合物，其化学式为[I]，其中每个符号的定义如规范中所述，或其药学上可接受的盐，以及一种丙型肝炎病毒（HCV）聚合酶抑制剂和治疗丙型肝炎的药物，本发明的化合物表现出基于HCV聚合酶抑制活性的抗HCV活性，因此可用作预防或治疗丙型肝炎的药物。