(R)-2-(1-氨基-2-甲基丙基)-3-苄基-7-氯-3H-喹唑啉-4-酮 | 336113-57-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: (R)-2-(1-氨基-2-甲基丙基)-3-苄基-7-氯-3H-喹唑啉-4-酮
• 英文名称: 2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one
• 英文别名: (R)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one；2-[(1R)-1-amino-2-methylpropyl]-3-benzyl-7-chloroquinazolin-4-one
• CAS: 336113-57-6
• 化学式: C₁₉H₂₀ClN₃O
• 分子量: 341.84
• InChiKey: OWYDWUOOPZRGNZ-QGZVFWFLSA-N

物化性质

• 沸点：
  510.9±60.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  58.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-(1-氨基-2-甲基丙基)-3-苄基-7-氯-3H-喹唑啉-4-酮 在 三乙酰氧基硼氢化钠 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 32.0h， 生成 N-(3-aminopropyl)-N-[(1R)-1-(3-benzyl-7-chloro-4-oxoquinazolin-2-yl)-2-methylpropyl]-4-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
• 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 、 氯化铵 、 O,O'-dibenzoyl-L-tartaric acid 、 锌 作用下， 以 甲醇 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 异丙醇 为溶剂， 反应 23.5h， 生成 (R)-2-(1-氨基-2-甲基丙基)-3-苄基-7-氯-3H-喹唑啉-4-酮
  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

• Oxidative Radical Skeletal Rearrangement Induced by Molecular Oxygen: Synthesis of Quinazolinones
  作者：Yi-Feng Wang、Feng-Lian Zhang、Shunsuke Chiba

  DOI：10.1021/ol4011745

  日期：2013.6.7

  Oxidative skeletal rearrangement of 5-aryl-4,5-dihydro-1,2,4-oxadiazoles into quinazolinones is induced by molecular oxygen (under a dry air atmosphere) that likely proceeds via transient iminyl radical species. Concise syntheses of biologically active quinazolinone derivatives were demonstrated using the present strategy.

  5-芳基-4,5-二氢-1,2,4-恶二唑的氧化骨架重排成喹唑啉酮是由分子氧（在干燥的空气气氛下）诱导的，该分子氧可能是通过瞬态亚氨基自由基进行的。使用本策略证明了生物活性喹唑啉酮衍生物的简明合成。
• 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。
• Compounds, compositions, and methods
  申请人：Feng Bainian

  公开号：US20060094735A1

  公开（公告）日：2006-05-04

  Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.

  本发明揭示了通过调节KSP的活性来治疗细胞增殖性疾病和障碍的有用化合物。
• Compounds, compositins, and methods
  申请人：Cytokinetics, Inc.

  公开号：US20040077668A1

  公开（公告）日：2004-04-22

  Compounds useful for treating cellular proliferative diseases and disorders by modulating the activity of KSP are disclosed.

  本发明揭示了通过调节KSP的活性来治疗细胞增殖性疾病和疾病的有用化合物。
• Metal-Dependent Cytotoxic and Kinesin Spindle Protein Inhibitory Activity of Ru, Os, Rh, and Ir Half-Sandwich Complexes of Ispinesib-Derived Ligands
  作者：Michał Łomzik、Muhammad Hanif、Aleksandra Budniok、Andrzej Błauż、Anna Makal、Daniel M. Tchoń、Barbara Leśniewska、Kelvin K. H. Tong、Sanam Movassaghi、Tilo Söhnel、Stephen M. F. Jamieson、Ayesha Zafar、Jóhannes Reynisson、Błażej Rychlik、Christian G. Hartinger、Damian Plażuk

  DOI：10.1021/acs.inorgchem.0c00957

  日期：2020.10.19

  identified as a promising target for antimitotic anticancer drugs. Herein, we report the synthesis of half-sandwich complexes of Ru, Os, Rh, and Ir bearing the ispinesib-derived N,N-bidentate ligands (R)- and (S)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4(3H)-one and studies on their chemical and biological properties. Using the enantiomerically pure (R)- and (S)-forms of the ligand, depending

  Ispinesib是驱动蛋白纺锤体蛋白（KSP）的有效抑制剂，已被确定为抗有丝分裂抗癌药物的有希望的靶标。在这里，我们报告Ru，Os，Rh和Ir的半三明治复合物的合成，该复合物带有异戊二烯衍生的N，N-双齿配体（R）-和（S）-2-（1-氨基-2-甲基丙基） ）-3-苄基-7-氯喹唑啉-4（3H）-及其化学和生物学性质的研究。使用对映体纯的（R）和（S）形式的配体，取决于有机金属部分，S M，R或R M，S非对映体，分别在RU-和Os（CYM）的分子结构中观察到（CYM =η 6 - p -cymene）化合物，而[R中号，[R或小号中号，š非对映体被发现为RH-和Ir（Cp *）（Cp * =η5-五甲基环戊二烯基）衍生物。但是，密度泛函理论（DFT）计算表明，非对映异构体之间的能量差非常小，因此溶液中将同时存在这两种混合物。有机金属化合物在一系列人类癌细胞系中表现出不同的抗增殖活性，其