6-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)hexanoic acid | 82603-64-3

• 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: 6-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)hexanoic acid
• 英文别名: 6-(2,4-dioxo-1H-quinazolin-3-yl)hexanoic acid
• CAS: 82603-64-3
• 化学式: C₁₄H₁₆N₂O₄
• mdl: MFCD05027533
• 分子量: 276.292
• InChiKey: DVGUQZCXAITIRY-UHFFFAOYSA-N

物化性质

• 密度：
  1.287±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  86.7
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  6-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)hexanoic acid 在 potassium carbonate 、 1-羟基苯并三唑 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 N-(2-aminophenyl)-6-(1-methyl-2,4-dioxoquinazolin-3-yl)hexanamide
  参考文献：
  名称：

  (2-Amino-phenyl)-amides of ω-substituted alkanoic acids as new histone deacetylase inhibitors

  摘要：

  A variety of omega-substituted alkanoic acid (2-amino-phenyl)-amides were designed and synthesized. These compounds were shown to inhibit recombinant human histone deacetylases (HDACs) with IC50 values in the low micromolar range and induce hyperacetylation of histones in whole cells. They induced expression of p21WAFl/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in this class showed efficacy in human tumor xenograft models. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.08.083
• 作为产物：
  描述：

  靛红酸酐 、 6-氨基己酸 在 三乙胺 、 甲酸 作用下， 以 水 为溶剂， 反应 9.0h， 以60%的产率得到6-(2,4-dioxo-1,4-dihydroquinazolin-3(2H)-yl)hexanoic acid
  参考文献：
  名称：

  Repositioning of Quinazolinedione-Based Compounds on Soluble Epoxide Hydrolase (sEH) through 3D Structure-Based Pharmacophore Model-Driven Investigation

  摘要：

  开发新的生物活性化合物是药物发现过程的主要目的之一。针对药理学相关的生物靶点，可以使用各种工具来确定新的候选药物，而寻找新的方法和手段往往是一个关键问题。在这种情况下，为了重新评估已经针对特定生物靶点显示出不良生物学效果的化合物，就更需要进行硅学药物重新定位程序。基于三维结构的药效学模型通常是针对特定靶点建立的，目的是加速鉴定新的有前途的化合物。在这项工作中，我们利用针对可溶性环氧化物水解酶（sEH）开发的基于三维结构的药效学模型，对内部合成的 190 种化合物库进行了重新评估。在所分析的化合物中，有一小部分喹唑啉二酮类分子最初是从虚拟组合库中挑选出来的，在针对热休克蛋白 90（Hsp90）进行初步研究时效果不佳。这些令人鼓舞的结果凸显了这一计算工作流程在加速药物发现/重新定位过程中的可靠性。

  DOI：

  10.3390/molecules27123866

文献信息

• (2-Amino-phenyl)-amides of ω-substituted alkanoic acids as new histone deacetylase inhibitors
  作者：Arkadii Vaisburg、Naomy Bernstein、Sylvie Frechette、Martin Allan、Elie Abou-Khalil、Silvana Leit、Oscar Moradei、Giliane Bouchain、James Wang、Soon Hyung Woo、Marielle Fournel、Pu T. Yan、Marie-Claude Trachy-Bourget、Ann Kalita、Carole Beaulieu、Zuomei Li、A.Robert MacLeod、Jeffrey M. Besterman、Daniel Delorme

  DOI：10.1016/j.bmcl.2003.08.083

  日期：2004.1

  A variety of omega-substituted alkanoic acid (2-amino-phenyl)-amides were designed and synthesized. These compounds were shown to inhibit recombinant human histone deacetylases (HDACs) with IC50 values in the low micromolar range and induce hyperacetylation of histones in whole cells. They induced expression of p21WAFl/Cip1 and caused cell-cycle arrest in human cancer cells. Compounds in this class showed efficacy in human tumor xenograft models. (C) 2003 Elsevier Ltd. All rights reserved.
• Repositioning of Quinazolinedione-Based Compounds on Soluble Epoxide Hydrolase (sEH) through 3D Structure-Based Pharmacophore Model-Driven Investigation
  作者：Erica Gazzillo、Stefania Terracciano、Dafne Ruggiero、Marianna Potenza、Maria Giovanna Chini、Gianluigi Lauro、Katrin Fischer、Robert Klaus Hofstetter、Assunta Giordano、Oliver Werz、Ines Bruno、Giuseppe Bifulco

  DOI：10.3390/molecules27123866

  日期：——

  The development of new bioactive compounds represents one of the main purposes of the drug discovery process. Various tools can be employed to identify new drug candidates against pharmacologically relevant biological targets, and the search for new approaches and methodologies often represents a critical issue. In this context, in silico drug repositioning procedures are required even more in order to re-evaluate compounds that already showed poor biological results against a specific biological target. 3D structure-based pharmacophoric models, usually built for specific targets to accelerate the identification of new promising compounds, can be employed for drug repositioning campaigns as well. In this work, an in-house library of 190 synthesized compounds was re-evaluated using a 3D structure-based pharmacophoric model developed on soluble epoxide hydrolase (sEH). Among the analyzed compounds, a small set of quinazolinedione-based molecules, originally selected from a virtual combinatorial library and showing poor results when preliminarily investigated against heat shock protein 90 (Hsp90), was successfully repositioned against sEH, accounting the related built 3D structure-based pharmacophoric model. The promising results here obtained highlight the reliability of this computational workflow for accelerating the drug discovery/repositioning processes.

  开发新的生物活性化合物是药物发现过程的主要目的之一。针对药理学相关的生物靶点，可以使用各种工具来确定新的候选药物，而寻找新的方法和手段往往是一个关键问题。在这种情况下，为了重新评估已经针对特定生物靶点显示出不良生物学效果的化合物，就更需要进行硅学药物重新定位程序。基于三维结构的药效学模型通常是针对特定靶点建立的，目的是加速鉴定新的有前途的化合物。在这项工作中，我们利用针对可溶性环氧化物水解酶（sEH）开发的基于三维结构的药效学模型，对内部合成的 190 种化合物库进行了重新评估。在所分析的化合物中，有一小部分喹唑啉二酮类分子最初是从虚拟组合库中挑选出来的，在针对热休克蛋白 90（Hsp90）进行初步研究时效果不佳。这些令人鼓舞的结果凸显了这一计算工作流程在加速药物发现/重新定位过程中的可靠性。