8-nitro-2-phenylquinazolin-4(3H)-one | 16239-39-7

• 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: 8-nitro-2-phenylquinazolin-4(3H)-one
• 英文别名: 8-nitro-2-phenyl-3H-quinazolin-4-one；8-Nitro-2-phenyl-3H-chinazolin-4-on；8-Nitro-2-phenyl-3H-chinazolon-(4)
• CAS: 16239-39-7
• 化学式: C₁₄H₉N₃O₃
• 分子量: 267.244
• InChiKey: SVUNQNLQMRANEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.91
• 重原子数：
  20.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  89.15
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  8-nitro-2-phenylquinazolin-4(3H)-one 、 2,2,2-trifluoroethyl(mesityl)iodonium trifluoromethanesulfonate 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 12.0h， 以61%的产率得到8-nitro-2-phenyl-4-(2,2,2-trifluoroethoxy)quinazoline
  参考文献：
  名称：

  喹唑啉酮类化合物的化学选择性三氟乙基化反应和光稳定性的鉴定

  摘要：

  在这里，我们报告在室温下使用三氟甲磺酸异氰酸酯（2,2,2-三氟乙基）碘鎓的未掩蔽的2-芳基喹唑啉-4（3 H）-酮的化学选择性三氟乙基化途径。同源C-，O-和N-官能化的子类以简单的方式访问，具有广泛的底物范围。这些化学选择性分支事件是由Pd催化的芳基侧基上的邻位C–H活化和酰胺基的碱促进的反应性调节驱动的，利用了喹唑啉4（3 H）的内在定向能力和竞争性亲核性。一个框架。此外，提出了与非辐射衰变相关的喹唑啉-4（3 H）-一族的出色光稳定性。

  DOI：

  10.1021/acs.joc.9b00470
• 作为产物：
  描述：

  苯甲酰氯 在 乙醇 、 氨 作用下， 生成 8-nitro-2-phenylquinazolin-4(3H)-one
  参考文献：
  名称：

  Zacharias, Journal fur praktische Chemie (Leipzig 1954), 1891, vol. <2> 43, p. 444

  摘要：

  DOI：

文献信息

• Direct diversification of unmasked quinazolin-4(3H)-ones through orthogonal reactivity modulation
  作者：Jae Bin Lee、Mi Eun Kang、Joohee Kim、Chang Young Lee、Jung-Min Kee、Kyungjae Myung、Jang-Ung Park、Sung You Hong

  DOI：10.1039/c7cc05794f

  日期：——

  An orthogonal reactivity modulation strategy affords diverse synthetic analogues from unmasked quinazolin-4(3H)-ones.

  一种正交反应调控策略使未掩蔽的喹唑啉-4(3H)-酮产生多样的合成类似物。
• Structure-based design, synthesis and crystallization of 2-arylquinazolines as lipid pocket ligands of p38α MAPK
  作者：Mike Bührmann、Bianca M. Wiedemann、Matthias P. Müller、Julia Hardick、Maria Ecke、Daniel Rauh

  DOI：10.1371/journal.pone.0184627

  日期：——

  disrupting protein-protein interactions. Small organic molecules that target these less conserved regions might serve as tools for chemical biology research and to probe alternative strategies in targeting protein kinases in disease settings. Here, we present the structure-based design and synthesis of a focused library of 2-arylquinazoline derivatives to target the lipophilic C-terminal binding pocket

  在蛋白激酶研究中，识别和解决除高度保守的ATP口袋以外的小分子结合位点引起了人们的极大兴趣，因为这一研究领域使我们对激酶功能的理解超出了催化磷酸转移的范围。此类替代结合位点可能涉及通过细微的构象变化来改变激活状态，控制细胞酶的定位或介导和破坏蛋白质-蛋白质相互作用。靶向这些保守程度较低的区域的有机小分子可作为化学生物学研究的工具，并探索针对疾病环境中蛋白激酶的替代策略。在这里，我们介绍了基于结构的设计和合成的2-芳基喹唑啉衍生物的聚焦库，以靶向p38中的亲脂性C末端结合口袋α MAPK，为获得清晰的生物功能尚未被识别。与p38的配体的相互作用α MAPK通过SPR测定分析，并用蛋白质X射线晶体学验证。
• Covalent Lipid Pocket Ligands Targeting p38α MAPK Mutants
  作者：Mike Bührmann、Julia Hardick、Jörn Weisner、Lena Quambusch、Daniel Rauh

  DOI：10.1002/anie.201706345

  日期：2017.10.16

  A chemical genetic approach is presented to covalently target a unique lipid binding pocket in the protein kinase p38α, whose function is not yet known. Based on a series of cocrystal structures, a library of 2‐arylquinazolines that were decorated with electrophiles were designed and synthesized to covalently target tailored p38α mutants containing artificially introduced cysteine residues. Matching

  提出了一种化学遗传方法来共价靶向蛋白激酶p38α中一个独特的脂质结合口袋，其功能尚不清楚。基于一系列共晶体结构，设计并合成了用亲电试剂修饰的2-芳基喹唑啉文库，以共价靶向含有人工引入的半胱氨酸残基的定制p38α突变体。通过MS分析鉴定出匹配的蛋白质-配体对，并通过MS / MS研究和蛋白质晶体学进一步验证。从这种方法中产生的共价配体对单个p38α突变体显示出极好的选择性，并将作为合适的探针在未来的生物学系统研究中通过药理学扰动来剖析脂质囊的功能。
• Ruthenium(II)-Catalyzed C–C/C–N Coupling of 2-Arylquinazolinones with Vinylene Carbonate: Access to Fused Quinazolinones
  作者：Zhao-Hui Wang、He Wang、Hua Wang、Lei Li、Ming-Dong Zhou

  DOI：10.1021/acs.orglett.0c04200

  日期：2021.2.5
• Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors
  作者：Liang Long、Yong-Heng Wang、Jun-Xiao Zhuo、Zheng-Chao Tu、Ruibo Wu、Min Yan、Quentin Liu、Gui Lu

  DOI：10.1016/j.ejmech.2018.08.053

  日期：2018.9

  Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly selective Aurora A inhibitors is difficult because Aurora A and B share high homology and differ only by three residues in their ATP-binding pockets. Through structure-based drug design, we designed and synthesized a series of novel quinazolin-4-amine derivatives. These derivatives act as selective Aurora A kinase inhibitors by exploiting the structural differences between Aurora A and B. The selectivities of most compounds were improved (the best up to >757-fold) when comparing with the lead compound (3-fold). In vitro biochemical and cellular assays revealed that compound 6 potently inhibited Aurora A kinase and most human tumor cells. Furthermore, compound 6 effectively suppressed carcinoma, such as triple-negative breast cancers (TNBC) in an animal model. Therefore, compound 6 might serve as a promising anticancer drug. Moreover, through molecular dynamic (MD) analysis, we have identified that a salt bridge formed in Aurora B is key contributor for the isoform selectivity of the inhibitor. This salt bridge has not been previously detected in the reported crystal structure of Aurora B. These results might provide a crucial basis for the further development of highly potent inhibitors with high selectivity for Aurora A. (C) 2018 Elsevier Masson SAS. All rights reserved.