8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester | 59868-49-4

• 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: 8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester
• 英文别名: 8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester；8-chloro-2,3,4,5-tetrahydro-1-benzazepine-2,5-dione-4-carboxylic acid methyl ester；methyl 8-chloro-2,5-dioxo-3,4-dihydro-1H-1-benzazepine-4-carboxylate
• CAS: 59868-49-4
• 化学式: C₁₂H₁₀ClNO₄
• 分子量: 267.669
• InChiKey: SIYVNVVHZFPMJL-UHFFFAOYSA-N

物化性质

• 沸点：
  469.7±45.0 °C(Predicted)
• 密度：
  1.389±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester 在 水 、 硝酸 、 potassium carbonate 作用下， 以 四氢呋喃 、 乙醇 、 二甲基亚砜 为溶剂， 反应 2.0h， 生成 9-chloro-2-[(3,4-dimethoxyphenyl)amino]-5H-benzo[b]pyrimido[5,4-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：

  methyl N-(3-carbomethoxypropionyl)-4-chloroanthranilate 在 potassium tert-butylate 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 8-chloro-2,5-dioxo-2,3,4,5-tetrahydro-1H-benzo[b]azepine-4-carboxylic acid methyl ester
  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

• 4-Carbamoyl-1-benzazepines as antiinflammatory agents
  申请人：Ciba-Geigy Corporation

  公开号：US03949081A1

  公开（公告）日：1976-04-06

  4-Arylcarbamoyl-2,3,4,5-tetrahydro-1-benzazepine-2,5-diones, e.g. those of the fromula ##SPC1## R = h, alkyl or aralkyl Ar = iso- or heterocyclic aryl R',r" = h, alkyl, alkanoyl, alkoxy, halogen or CF.sub.3 alkali metal or acid addition salts thereof are antiinflammatory agents.

  4-芳基氨基甲酰基-2,3,4,5-四氢-1-苯并氮杂环-2,5-二酮，例如公式## SPC1 ## R =氢，烷基或芳基烷基Ar =异构或杂环芳基R'，r "=氢，烷基，烷酰基，烷氧基，卤素或CF.sub.3碱金属或酸加成盐为抗炎剂。
• 4-Carbamoyl-1-benzazepines
  申请人：Ciba-Geigy Corporation

  公开号：US03989689A1

  公开（公告）日：1976-11-02

  4-Arylcarbamoyl-2,3,4,5-tetrahydro-1-benzazepine-2,5-diones, e.g. those of the formula ##SPC1## R = h, alkyl or aralkyl Ar = iso- or heterocyclic aryl R',r" = h, alkyl, alkanoyl, alkoxy, halogen or CF.sub.3 alkali metal or acid addition salts thereof are antiinflammatory agents.

  4-芳基氨基甲酰基-2,3,4,5-四氢-1-苯并咪唑-2,5-二酮，例如公式##SPC1## R = 氢，烷基或芳基烷基 Ar = 异构或杂环芳基 R'，r" = 氢，烷基，脂肪酰基，烷氧基，卤素或CF.sub.3 它们的碱金属或酸盐是抗炎药物。
• 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。
• LACTAM COMPOUNDS USEFUL AS PROTEIN KINASE INHIBITORS
  申请人：Blackburn Christopher

  公开号：US20120178739A1

  公开（公告）日：2012-07-12

  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所述化合物的药物组合物，以及使用该组合物治疗各种疾病的方法。
• US3989689A
  申请人：——

  公开号：US3989689A

  公开（公告）日：1976-11-02