(R)-[3-[[1-(3-苄基-7-氯-4-氧代-3,4-二氢喹唑啉-2-基)-2-甲基丙基](4-甲基苯甲酰基)氨基]丙基]氨基甲酸叔丁酯 | 587881-28-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (R)-[3-[[1-(3-苄基-7-氯-4-氧代-3,4-二氢喹唑啉-2-基)-2-甲基丙基](4-甲基苯甲酰基)氨基]丙基]氨基甲酸叔丁酯
• 英文名称: tert-butyl (3-(N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamido)propyl)carbamate
• 英文别名: (R)-tert-butyl (3-(N-(1-(3-benzyl-7-chloro-4-oxo-3,4-dihydroquinazolin-2-yl)-2-methylpropyl)-4-methylbenzamido)propyl)carbamate；tert-butyl N-[3-[[(1R)-1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-(4-methylbenzoyl)amino]propyl]carbamate
• CAS: 587881-28-5
• 化学式: C₃₅H₄₁ClN₄O₄
• 分子量: 617.188
• InChiKey: DCSJTRHNJQALDQ-SSEXGKCCSA-N

物化性质

• 密度：
  1.18

计算性质

• 辛醇/水分配系数(LogP)：
  7
• 重原子数：
  44
• 可旋转键数：
  12
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  91.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-[3-[[1-(3-苄基-7-氯-4-氧代-3,4-二氢喹唑啉-2-基)-2-甲基丙基](4-甲基苯甲酰基)氨基]丙基]氨基甲酸叔丁酯 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以85%的产率得到伊斯平斯
  参考文献：
  名称：

  Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression

  摘要：

  Anti-mitotic anti-cancer drugs offer a potential platform for developing new radiotracers for imaging proliferation markers associated with the mitosis-phase of the cell-cycle. One interesting target is kinesin spindle protein (KSP)-an ATP-dependent motor protein that plays a vital role in bipolar spindle formation. In this work we synthesised a range of new fluorinated-quinazolinone compounds based on the structure of the clinical candidate KSP inhibitor, ispinesib, and investigated their properties in vitro as potential anti-mitotic agents targeting KSP expression. Anti-proliferation (MTT and BrdU) assays combined with additional studies including fluorescence-assisted cell sorting (FACS) analysis of cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Additional studies using confocal fluorescence microscopy showed that these compounds induce M-phase arrest via monoaster spindle formation. Structural studies revealed that compound 20-(R) is the most potent fluorinated-quinazolinone inhibitor of KSP and represents a suitable lead candidate for further studies on designing F-18-radiolabelled agents for positron-emission tomography (PET). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.013
• 作为产物：
  描述：

  3-苄基-2-(1-溴-2-甲基丙基)-7-氯喹唑啉-4-酮 在 sodium azide 、 三乙酰氧基硼氢化钠 、 氯化铵 、 N,N-二异丙基乙胺 、 O,O'-dibenzoyl-L-tartaric acid 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 乙酸乙酯 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 53.5h， 生成 (R)-[3-[[1-(3-苄基-7-氯-4-氧代-3,4-二氢喹唑啉-2-基)-2-甲基丙基](4-甲基苯甲酰基)氨基]丙基]氨基甲酸叔丁酯
  参考文献：
  名称：

  Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression

  摘要：

  Anti-mitotic anti-cancer drugs offer a potential platform for developing new radiotracers for imaging proliferation markers associated with the mitosis-phase of the cell-cycle. One interesting target is kinesin spindle protein (KSP)-an ATP-dependent motor protein that plays a vital role in bipolar spindle formation. In this work we synthesised a range of new fluorinated-quinazolinone compounds based on the structure of the clinical candidate KSP inhibitor, ispinesib, and investigated their properties in vitro as potential anti-mitotic agents targeting KSP expression. Anti-proliferation (MTT and BrdU) assays combined with additional studies including fluorescence-assisted cell sorting (FACS) analysis of cell-cycle arrest confirmed the mechanism and potency of these biphenyl compounds in a range of human cancer cell lines. Additional studies using confocal fluorescence microscopy showed that these compounds induce M-phase arrest via monoaster spindle formation. Structural studies revealed that compound 20-(R) is the most potent fluorinated-quinazolinone inhibitor of KSP and represents a suitable lead candidate for further studies on designing F-18-radiolabelled agents for positron-emission tomography (PET). (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.11.013

文献信息

• Syntheses of quinazolinones
  申请人：——

  公开号：US20040067969A1

  公开（公告）日：2004-04-08

  The present invention provides intermediates, synthetic methods and novel quinazolinone compositions of matter.

  本发明提供了中间体、合成方法和新型喹唑啉酮组合物。
• SYNTHESES OF QUINAZOLINONES
  申请人：Cytokinetics, Inc.

  公开号：EP1480980A2

  公开（公告）日：2004-12-01
• EP1480980A4
  申请人：——

  公开号：EP1480980A4

  公开（公告）日：2005-04-20
• US7009049B2
  申请人：——

  公开号：US7009049B2

  公开（公告）日：2006-03-07
• US7161002B2
  申请人：——

  公开号：US7161002B2

  公开（公告）日：2007-01-09