9-chloro-2-({3-[3-(dimethylamino)propyl]phenyl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione | 1350816-01-1

• 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: 9-chloro-2-({3-[3-(dimethylamino)propyl]phenyl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione
• 英文别名: 9-Chloro-2-[3-[3-(dimethylamino)propyl]anilino]-5,7-dihydropyrimido[5,4-d][1]benzazepine-6-thione
• CAS: 1350816-01-1
• 化学式: C₂₃H₂₄ClN₅S
• 分子量: 437.996
• InChiKey: QUFVOKRHVJFMNM-UHFFFAOYSA-N

物化性质

• 沸点：
  631.3±65.0 °C(predicted)
• 密度：
  1.34±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-chloro-2-({3-[3-(dimethylamino)propyl]phenyl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione 在 盐酸 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 0.67h， 以88%的产率得到9-chloro-2-({3-[3-(dimethylamino)propyl]phenyl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione dihydrochloride
  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 吡啶 、 tris-(dibenzylideneacetone)dipalladium(0) 、 tetraphosphorus decasulfide 、 水 、 potassium carbonate 、 caesium carbonate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二甲基亚砜 为溶剂， 反应 3.17h， 生成 9-chloro-2-({3-[3-(dimethylamino)propyl]phenyl}amino)-5,7-dihydro-6H-pyrimido[5,4-d][1]benzazepine-6-thione
  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

• 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.