3-(benzyloxy)-7-chloro-1H-quinazoline-2,4(1H,3H)-dione | 705977-17-9

• 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-chloro-1H-quinazoline-2,4(1H,3H)-dione
• CAS: 705977-17-9
• 化学式: C₁₅H₁₁ClN₂O₃
• 分子量: 302.717
• InChiKey: OHIHFYXOOJMFPF-UHFFFAOYSA-N

物化性质

• 熔点：
  294-295 °C(Solvent: Ethanol)
• 密度：
  1.47±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.97
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  64.09
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  3-(benzyloxy)-7-chloro-1H-quinazoline-2,4(1H,3H)-dione 在 palladium on activated charcoal 吡啶 、 三甲基氯硅烷 、 氢溴酸 、 氢气 、 硝酸 、 三乙胺 作用下， 以 溶剂黄146 、 乙酸乙酯 为溶剂， -10.0~100.0 ℃ 、275.79 kPa 条件下， 生成 Acetic acid 7-chloro-2,4-dioxo-6-[1,2,4]triazol-4-yl-1,4-dihydro-2H-quinazolin-3-yl ester
  参考文献：
  名称：

  3-Hydroxy-quinazoline-2,4-dione as a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists

  摘要：

  The synthesis and Gly/NMDA, AMPA and KA receptor binding activities of some 3-hydroxy-quinazoline-2,4-dione derivatives are reported. The binding data, together with functional antagonism studies, showed that the 3-hydroxy-quinazoline-2,4-dione moiety can be considered a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists. In fact, introduction of chlorine atom(s) on precise position(s) of the benzofused moiety yielded Gly/NMDA selective antagonists, while the presence of the 6-(1,2,4-triazol-4-yl) group shifted the affinity and selectivity towards the AMPA receptor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.109
• 作为产物：
  描述：

  4-氯靛红酸酐 在 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 生成 3-(benzyloxy)-7-chloro-1H-quinazoline-2,4(1H,3H)-dione
  参考文献：
  名称：

  3-Hydroxy-quinazoline-2,4-dione as a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists

  摘要：

  The synthesis and Gly/NMDA, AMPA and KA receptor binding activities of some 3-hydroxy-quinazoline-2,4-dione derivatives are reported. The binding data, together with functional antagonism studies, showed that the 3-hydroxy-quinazoline-2,4-dione moiety can be considered a useful scaffold to obtain selective Gly/NMDA and AMPA receptor antagonists. In fact, introduction of chlorine atom(s) on precise position(s) of the benzofused moiety yielded Gly/NMDA selective antagonists, while the presence of the 6-(1,2,4-triazol-4-yl) group shifted the affinity and selectivity towards the AMPA receptor. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.01.109

文献信息

• 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。