1-(2-(3-(3-Chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-ylthio)-2-phenylacetyl)piperidine-4-carboxamide | 1146625-42-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-(2-(3-(3-Chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-ylthio)-2-phenylacetyl)piperidine-4-carboxamide
• 英文别名: 1-[2-[3-(3-chlorophenyl)-4-oxoquinazolin-2-yl]sulfanyl-2-phenylacetyl]piperidine-4-carboxamide
• CAS: 1146625-42-4
• 化学式: C₂₈H₂₅ClN₄O₃S
• 分子量: 533.051
• InChiKey: DGNIAKAILQEBDR-UHFFFAOYSA-N

物化性质

• 沸点：
  789.2±70.0 °C(predicted)
• 密度：
  1.40±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  哌啶-4-甲酰胺 、 2-((3-(3-chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-yl)thio)-2-phenylacetic acid 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 1-(2-(3-(3-Chlorophenyl)-4-oxo-3,4-dihydroquinazolin-2-ylthio)-2-phenylacetyl)piperidine-4-carboxamide
  参考文献：
  名称：

  Development of thioquinazolinones, allosteric Chk1 kinase inhibitors

  摘要：

  A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.

  DOI：

  10.1016/j.bmcl.2008.12.076

文献信息

• [EN] INHIBITORS OF CHECKPOINT KINASES<br/>[FR] INHIBITEURS DE CHECKPOINT KINASES
  申请人：MERCK & CO INC

  公开号：WO2009102537A1

  公开（公告）日：2009-08-20

  The instant invention provides for compounds which comprise substituted thioquinazolinones that inhibit CHK1 activity. The invention also provides for compositions comprising such inhibitory compounds and methods of inhibiting CHK1 activity by administering the compound to a patient in need of treatment of cancer.

  这项即时发明提供了包含替代硫喹唑酮的化合物，这些化合物抑制CHK1活性。该发明还提供了包含这种抑制性化合物的组合物，以及通过向需要癌症治疗的患者施用该化合物来抑制CHK1活性的方法。
• Development of thioquinazolinones, allosteric Chk1 kinase inhibitors
  作者：Antonella Converso、Timothy Hartingh、Robert M. Garbaccio、Edward Tasber、Keith Rickert、Mark E. Fraley、Youwei Yan、Constantine Kreatsoulas、Steve Stirdivant、Bob Drakas、Eileen S. Walsh、Kelly Hamilton、Carolyn A. Buser、Xianzhi Mao、Marc T. Abrams、Stephen C. Beck、Weikang Tao、Rob Lobell、Laura Sepp-Lorenzino、Joan Zugay-Murphy、Vinod Sardana、Sanjeev K. Munshi、Sylvie Marie Jezequel-Sur、Paul D. Zuck、George D. Hartman

  DOI：10.1016/j.bmcl.2008.12.076

  日期：2009.2

  A high throughput screening campaign was designed to identify allosteric inhibitors of Chk1 kinase by testing compounds at high concentration. Activity was then observed at K(m) for ATP and at near-physiological concentrations of ATP. This strategy led to the discovery of a non-ATP competitive thioquinazolinone series which was optimized for potency and stability. An X-ray crystal structure for the complex of our best inhibitor bound to Chk1 was solved, indicating that it binds to an allosteric site approximately 13A from the ATP binding site. Preliminary data is presented for several of these compounds.