9-chloro-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5H-benzo[b]pyrimido[4,5-d]azepin-6(7H)-one | 1350815-91-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 9-chloro-2-(4-(4-methylpiperazin-1-yl)phenylamino)-5H-benzo[b]pyrimido[4,5-d]azepin-6(7H)-one
• 英文别名: 9-Chloro-2-[4-(4-methylpiperazin-1-yl)anilino]-5,7-dihydropyrimido[5,4-d][1]benzazepin-6-one
• CAS: 1350815-91-6
• 化学式: C₂₃H₂₃ClN₆O
• 分子量: 434.928
• InChiKey: LIXHSYCKAGJUFP-UHFFFAOYSA-N

物化性质

• 密度：
  1.341±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  73.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 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 、 sodium ethanolate 、 N,N-二异丙基乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 为溶剂， 反应 3.33h， 生成 9-chloro-2-(4-(4-methylpiperazin-1-yl)phenylamino)-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

文献信息

• 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。
• US7459448B2
  申请人：——

  公开号：US7459448B2

  公开（公告）日：2008-12-02
• US7935694B2
  申请人：——

  公开号：US7935694B2

  公开（公告）日：2011-05-03
• Discovery of a Potent and Orally Bioavailable Benzolactam-Derived Inhibitor of Polo-Like Kinase 1 (MLN0905)
  作者：Matthew O. Duffey、Tricia J. Vos、Ruth Adams、Jennifer Alley、Justin Anthony、Cynthia Barrett、Indu Bharathan、Douglas Bowman、Nancy J. Bump、Ryan Chau、Courtney Cullis、Denise L. Driscoll、Amy Elder、Nancy Forsyth、Jonathan Frazer、Jianping Guo、Luyi Guo、Marc L. Hyer、David Janowick、Bheemashankar Kulkarni、Su-Jen Lai、Kerri Lasky、Gang Li、Jing Li、Debra Liao、Jeremy Little、Bo Peng、Mark G. Qian、Dominic J. Reynolds、Mansoureh Rezaei、Margaret Porter Scott、Todd B. Sells、Vaishali Shinde、Qiuju Judy Shi、Michael D. Sintchak、Francois Soucy、Kevin T. Sprott、Stephen G. Stroud、Michelle Nestor、Irache Visiers、Gabriel Weatherhead、Yingchun Ye、Natalie D’Amore

  DOI：10.1021/jm2011172

  日期：2012.1.12

  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.