1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethanone oxime | 918804-18-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethanone oxime
• 英文别名: N-[1-(2,3-Dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethylidene]hydroxylamine；N-[1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethylidene]hydroxylamine
• CAS: 918804-18-9
• 化学式: C₁₆H₁₅NO₄
• 分子量: 285.299
• InChiKey: UHZYRXKBCHHWRB-UHFFFAOYSA-N

物化性质

• 沸点：
  470.8±45.0 °C(Predicted)
• 密度：
  1.26±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  60.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethanone oxime 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以0.52 g的产率得到1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethylamine
  参考文献：
  名称：

  Discovering Potassium Channel Blockers from Synthetic Compound Database by Using Structure-Based Virtual Screening in Conjunction with Electrophysiological Assay

  摘要：

  Potassium ion (K+) channels are attractive targets for drug discovery because of the essential roles played in biological systems. However, high-throughput screening (HTS) cannot be used to screen K+ channel blockers. To overcome this disadvantage of HTS, we have developed a virtual screening approach for discovering novel blockers of K+ channels. On the basis of a three-dimensional model of the eukaryotic K+ channels, molecular docking-based virtual screening was employed to search the chemical database MDL Available Chemicals Directory (ACD). Compounds were ranked according to their relative binding energy, favorable shape complementarity, and potential to form hydrogen bonds with the outer mouth of the K+ channel model. Twenty candidate compounds selected from the virtual screening were examined using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. Among them, six compounds (5, 6, 8, 18-20) potently blocked both the delayed rectifier (I-K) and fast transient K+ currents (I-A). When applied externally, these six compounds preferentially blocked I-K with potencies 2- to 500-fold higher than that of tetraethylammonium chloride. Intracellular application of the six compounds had no effect on both K+ currents. In addition, the interaction models and binding free energy calculations demonstrated that hydrophobic interaction and solvent effects play important roles in the inhibitory activities of these compounds. The results demonstrated that structure-based computer screening strategy could be used to identify novel, structurally diverse compounds targeting the pore binding pocket of the outer mouth of voltage-gated K+ channels. This study provides an alternative way of finding new blockers of voltage-gated K+ channels, while the techniques for high-throughput screening of K+ channel drugs remain in development.

  DOI：

  10.1021/jm060414o
• 作为产物：
  描述：

  2-溴-1-(2,3-二氢-1,4-苯并二氧)乙酮 在 盐酸羟胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 5.0h， 生成 1-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-phenoxyethanone oxime
  参考文献：
  名称：

  Discovering Potassium Channel Blockers from Synthetic Compound Database by Using Structure-Based Virtual Screening in Conjunction with Electrophysiological Assay

  摘要：

  Potassium ion (K+) channels are attractive targets for drug discovery because of the essential roles played in biological systems. However, high-throughput screening (HTS) cannot be used to screen K+ channel blockers. To overcome this disadvantage of HTS, we have developed a virtual screening approach for discovering novel blockers of K+ channels. On the basis of a three-dimensional model of the eukaryotic K+ channels, molecular docking-based virtual screening was employed to search the chemical database MDL Available Chemicals Directory (ACD). Compounds were ranked according to their relative binding energy, favorable shape complementarity, and potential to form hydrogen bonds with the outer mouth of the K+ channel model. Twenty candidate compounds selected from the virtual screening were examined using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. Among them, six compounds (5, 6, 8, 18-20) potently blocked both the delayed rectifier (I-K) and fast transient K+ currents (I-A). When applied externally, these six compounds preferentially blocked I-K with potencies 2- to 500-fold higher than that of tetraethylammonium chloride. Intracellular application of the six compounds had no effect on both K+ currents. In addition, the interaction models and binding free energy calculations demonstrated that hydrophobic interaction and solvent effects play important roles in the inhibitory activities of these compounds. The results demonstrated that structure-based computer screening strategy could be used to identify novel, structurally diverse compounds targeting the pore binding pocket of the outer mouth of voltage-gated K+ channels. This study provides an alternative way of finding new blockers of voltage-gated K+ channels, while the techniques for high-throughput screening of K+ channel drugs remain in development.

  DOI：

  10.1021/jm060414o

文献信息

• US8012901B1
  申请人：——

  公开号：US8012901B1

  公开（公告）日：2011-09-06
• Discovering Potassium Channel Blockers from Synthetic Compound Database by Using Structure-Based Virtual Screening in Conjunction with Electrophysiological Assay
  作者：Hong Liu、Zhao-Bing Gao、Zhiyi Yao、Suxin Zheng、Yang Li、Weiliang Zhu、Xiaojian Tan、Xiaomin Luo、Jianhua Shen、Kaixian Chen、Guo-Yuan Hu、Hualiang Jiang

  DOI：10.1021/jm060414o

  日期：2007.1.1

  Potassium ion (K+) channels are attractive targets for drug discovery because of the essential roles played in biological systems. However, high-throughput screening (HTS) cannot be used to screen K+ channel blockers. To overcome this disadvantage of HTS, we have developed a virtual screening approach for discovering novel blockers of K+ channels. On the basis of a three-dimensional model of the eukaryotic K+ channels, molecular docking-based virtual screening was employed to search the chemical database MDL Available Chemicals Directory (ACD). Compounds were ranked according to their relative binding energy, favorable shape complementarity, and potential to form hydrogen bonds with the outer mouth of the K+ channel model. Twenty candidate compounds selected from the virtual screening were examined using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. Among them, six compounds (5, 6, 8, 18-20) potently blocked both the delayed rectifier (I-K) and fast transient K+ currents (I-A). When applied externally, these six compounds preferentially blocked I-K with potencies 2- to 500-fold higher than that of tetraethylammonium chloride. Intracellular application of the six compounds had no effect on both K+ currents. In addition, the interaction models and binding free energy calculations demonstrated that hydrophobic interaction and solvent effects play important roles in the inhibitory activities of these compounds. The results demonstrated that structure-based computer screening strategy could be used to identify novel, structurally diverse compounds targeting the pore binding pocket of the outer mouth of voltage-gated K+ channels. This study provides an alternative way of finding new blockers of voltage-gated K+ channels, while the techniques for high-throughput screening of K+ channel drugs remain in development.