N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-3-fluorobenzamide | 1417617-17-4

• 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: N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-3-fluorobenzamide
• CAS: 1417617-17-4
• 化学式: C₂₉H₃₀ClFN₄O₂
• 分子量: 521.034
• InChiKey: MHAHUTAEMRYGPD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  37
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  79
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 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 、 三氟乙酸 、 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 为溶剂， 反应 37.5h， 生成 N-(3-aminopropyl)-N-[1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-3-fluorobenzamide
  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

• Fluorinated quinazolinones as potential radiotracers for imaging kinesin spindle protein expression
  作者：Jason P. Holland、Michael W. Jones、Susan Cohrs、Roger Schibli、Eliane Fischer

  DOI：10.1016/j.bmc.2012.11.013

  日期：2013.1

  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.