3-benzyloxy-7-trifluoromethyl-1H-quinazoline-2,4-dione | 1394058-47-9

• 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: 3-benzyloxy-7-trifluoromethyl-1H-quinazoline-2,4-dione
• 英文别名: 3-phenylmethoxy-7-(trifluoromethyl)-1H-quinazoline-2,4-dione
• CAS: 1394058-47-9
• 化学式: C₁₆H₁₁F₃N₂O₃
• 分子量: 336.27
• InChiKey: QSLRPPGDIQMEQK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  58.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  3-benzyloxy-7-trifluoromethyl-1H-quinazoline-2,4-dione 在 氢溴酸 、 溶剂黄146 作用下， 以 水 为溶剂， 反应 5.0h， 生成 3-acetoxy-7-trifluoromethyl-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  3-Hydroxy-1H-quinazoline-2,4-dione derivatives as new antagonists at ionotropic glutamate receptors: Molecular modeling and pharmacological studies

  摘要：

  Based on our 3-hydroxy-7-chloroquinazoline-2,4-dione derivatives, previously reported as antagonists at ionotropic glutamate receptors, we synthesized new 3-hydroxyquinazoline-2,4-diones bearing a trifluoromethyl group at the 7-position and different groups at position 6. Glycine/NMDA, AMPA and kainate receptor binding data showed that the 7-trifluoromethyl residue increased AMPA and kainate receptor affinity and selectivity, with respect to the 7-chlorine atom. Among the probed 6-substituents, the 6-(1,2,4-triazol-4-yl) group (compound 8) was the most advantageous for AMPA receptor affinity and selectivity. Derivative 8 demonstrated to be effective in decreasing neuronal damage produced by oxygen and glucose deprivation in organotypic rat hippocampal slices and also showed anticonvulsant effects in pentylenetetrazole-induced convulsions. The previously reported kainate receptor antagonist 6-(2-carboxybenzoyl)-amino-7-chloro-3-hydroxyquinazoline-2,4-dione 3 prevented the failure of neurotransmission induced by oxygen and glucose deprivation in the CA1 region of rat hippocampal slices. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.05.036
• 作为产物：
  描述：

  三光气 、 2-amino-N-(benzyloxy)-4-trifluoromethylbenzamide 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 3-benzyloxy-7-trifluoromethyl-1H-quinazoline-2,4-dione
  参考文献：
  名称：

  3-Hydroxy-1 H -quinazoline-2,4-dione作为开发与肿瘤相关的碳酸酐酶IX和XII的有效和选择性抑制剂的新型支架。

  摘要：

  在本文中，我们描述了3-羟基喹唑啉-2,4-二酮作为获得与肿瘤相关的人类碳酸酐酶（hCAs）IX和XII的有效抑制剂的有用支架的发现。一组衍生物（1 - 29），轴承上的稠合苯并环不同的取代基（氯，NO 2，NH 2，CF 3基，脲基，酰氨基，杂环），合成，并在抑制其中几个显示纳摩尔活性hCA IX和XII亚型，尽管它们对细胞溶质酶hCAs I和II无效。测试了一些选择的化合物对HT-29结肠癌细胞系的抗增殖活性。用较低剂量（30μM）处理48小时后，衍生物12，14，15，和19分别为显著活性，约50％在两个常氧和低氧诱导的死亡率。这一发现使我们为这些化合物假设了涉及CA IX和XII以及其他尚未确定的靶标的一种以上的作用机理。

  DOI：

  10.1021/acs.jmedchem.7b00766

文献信息

• 3-Hydroxy-1H-quinazoline-2,4-dione derivatives as new antagonists at ionotropic glutamate receptors: Molecular modeling and pharmacological studies
  作者：Vittoria Colotta、Ombretta Lenzi、Daniela Catarzi、Flavia Varano、Lucia Squarcialupi、Chiara Costagli、Alessandro Galli、Carla Ghelardini、Anna Maria Pugliese、Giovanna Maraula、Elisabetta Coppi、Domenico E. Pellegrini-Giampietro、Felicita Pedata、Davide Sabbadin、Stefano Moro

  DOI：10.1016/j.ejmech.2012.05.036

  日期：2012.8

  Based on our 3-hydroxy-7-chloroquinazoline-2,4-dione derivatives, previously reported as antagonists at ionotropic glutamate receptors, we synthesized new 3-hydroxyquinazoline-2,4-diones bearing a trifluoromethyl group at the 7-position and different groups at position 6. Glycine/NMDA, AMPA and kainate receptor binding data showed that the 7-trifluoromethyl residue increased AMPA and kainate receptor affinity and selectivity, with respect to the 7-chlorine atom. Among the probed 6-substituents, the 6-(1,2,4-triazol-4-yl) group (compound 8) was the most advantageous for AMPA receptor affinity and selectivity. Derivative 8 demonstrated to be effective in decreasing neuronal damage produced by oxygen and glucose deprivation in organotypic rat hippocampal slices and also showed anticonvulsant effects in pentylenetetrazole-induced convulsions. The previously reported kainate receptor antagonist 6-(2-carboxybenzoyl)-amino-7-chloro-3-hydroxyquinazoline-2,4-dione 3 prevented the failure of neurotransmission induced by oxygen and glucose deprivation in the CA1 region of rat hippocampal slices. (C) 2012 Elsevier Masson SAS. All rights reserved.
• 3-Hydroxy-1<i>H</i>-quinazoline-2,4-dione as a New Scaffold To Develop Potent and Selective Inhibitors of the Tumor-Associated Carbonic Anhydrases IX and XII
  作者：Matteo Falsini、Lucia Squarcialupi、Daniela Catarzi、Flavia Varano、Marco Betti、Lorenzo Di Cesare Mannelli、Barbara Tenci、Carla Ghelardini、Muhammet Tanc、Andrea Angeli、Claudiu T. Supuran、Vittoria Colotta

  DOI：10.1021/acs.jmedchem.7b00766

  日期：2017.7.27

  In this paper, we describe the discovery of the 3-hydroxyquinazoline-2,4-dione as a useful scaffold to obtain potent inhibitors of the tumor-associated human carbonic anhydrases (hCAs) IX and XII. A set of derivatives (1–29), bearing different substituents on the fused benzo ring (Cl, NO2, NH2, CF3, ureido, amido, heterocycles), were synthesized, and several of them showed nanomolar activity in inhibiting

  在本文中，我们描述了3-羟基喹唑啉-2,4-二酮作为获得与肿瘤相关的人类碳酸酐酶（hCAs）IX和XII的有效抑制剂的有用支架的发现。一组衍生物（1 - 29），轴承上的稠合苯并环不同的取代基（氯，NO 2，NH 2，CF 3基，脲基，酰氨基，杂环），合成，并在抑制其中几个显示纳摩尔活性hCA IX和XII亚型，尽管它们对细胞溶质酶hCAs I和II无效。测试了一些选择的化合物对HT-29结肠癌细胞系的抗增殖活性。用较低剂量（30μM）处理48小时后，衍生物12，14，15，和19分别为显著活性，约50％在两个常氧和低氧诱导的死亡率。这一发现使我们为这些化合物假设了涉及CA IX和XII以及其他尚未确定的靶标的一种以上的作用机理。