4-((6-((4-fluorobenzyl)amino)-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy)benzonitrile | 1370706-02-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 4-((6-((4-fluorobenzyl)amino)-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy)benzonitrile
• 英文别名: 4-[[6-[(4-fluorophenyl)methylamino]-2,4-dimethyl-3H-1,4-benzoxazin-2-yl]methoxy]benzonitrile
• CAS: 1370706-02-7
• 化学式: C₂₅H₂₄FN₃O₂
• 分子量: 417.483
• InChiKey: GZAQTQFVZIWJNE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  57.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4-((6-((4-fluorobenzyl)amino)-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy)benzonitrile 在 盐酸 、 三乙胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 52.5h， 生成 2-((2-((4-carbamimidoylphenoxy)methyl)-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-6-yl)(4-fluorobenzyl)amino)-2-oxoacetic acid
  参考文献：
  名称：

  Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold

  摘要：

  Fluorinated 3,4-dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activities were prepared as potential dual antithrombotic compounds. Fluorine scan (3-fluorobenzyl, 4-fluorobenzyl, 3,4-difluorobenzyl and 3,5-difluorobenzyl substituted compounds) was performed in order to obtain 6-(carboxymethyl)(3,4-difluorobenzyl) amino compound (9i) as the most potent compound with balanced dual activity (K-i(Thr) = 0.33 +/- 0.07 mu M, IC50(GP IIb/IIIa) = 1.1 +/- 0.6 mu M). (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.01.059
• 作为产物：
  描述：

  2-氨基-4-硝基苯酚 在 potassium fluoride 、 sodium triacetoxyborohydride 、 偶氮二甲酸二异丙酯 、 dimethyl sulfide borane 、 palladium on carbon 、 氢气 、 三苯基膦 作用下， 以 四氢呋喃 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 68.0h， 生成 4-((6-((4-fluorobenzyl)amino)-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methoxy)benzonitrile
  参考文献：
  名称：

  Thrombin inhibitors with lipid peroxidation and lipoxygenase inhibitory activities

  摘要：

  Vascular oxidative stress, endothelial injury, and thrombosis are intertwined processes that display a synergistic pathological effect in many cardiovascular diseases. Antithrombotic therapy with anticoagulant and/or antiplatelet agents, combined with interventions against vascular oxidative stress and/or inflammation, both boosting endothelial antithrombotic potential, could display a synergistic action in the treatment of thrombosis. Of the compounds 10a-h and 11a-d, shown to possess thrombin inhibitory activity, 11a-d were found to display radical scavenging activity, 10a, 10d, and 10f were demonstrated to inhibit lipid peroxidation of linoleic acid, and 10b and 10h inhibited soybean lipoxygenase. The observed combination of thrombin inhibition with lipid peroxidation and/or lipoxygenase inhibitory activity makes compounds 10 and 11 interesting candidates for further investigations towards multiple antithrombotic drugs. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.06.089

文献信息

• Thrombin inhibitors with lipid peroxidation and lipoxygenase inhibitory activities
  作者：Miloš Ilić、Christos Kontogiorgis、Dimitra Hadjipavlou-Litina、Janez Ilaš、Danijel Kikelj

  DOI：10.1016/j.bmcl.2011.06.089

  日期：2011.8

  Vascular oxidative stress, endothelial injury, and thrombosis are intertwined processes that display a synergistic pathological effect in many cardiovascular diseases. Antithrombotic therapy with anticoagulant and/or antiplatelet agents, combined with interventions against vascular oxidative stress and/or inflammation, both boosting endothelial antithrombotic potential, could display a synergistic action in the treatment of thrombosis. Of the compounds 10a-h and 11a-d, shown to possess thrombin inhibitory activity, 11a-d were found to display radical scavenging activity, 10a, 10d, and 10f were demonstrated to inhibit lipid peroxidation of linoleic acid, and 10b and 10h inhibited soybean lipoxygenase. The observed combination of thrombin inhibition with lipid peroxidation and/or lipoxygenase inhibitory activity makes compounds 10 and 11 interesting candidates for further investigations towards multiple antithrombotic drugs. (C) 2011 Elsevier Ltd. All rights reserved.
• Fluorinated dual antithrombotic compounds based on 1,4-benzoxazine scaffold
  作者：Miloš Ilić、Danijel Kikelj、Janez Ilaš

  DOI：10.1016/j.ejmech.2012.01.059

  日期：2012.4

  Fluorinated 3,4-dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa receptor antagonistic activities were prepared as potential dual antithrombotic compounds. Fluorine scan (3-fluorobenzyl, 4-fluorobenzyl, 3,4-difluorobenzyl and 3,5-difluorobenzyl substituted compounds) was performed in order to obtain 6-(carboxymethyl)(3,4-difluorobenzyl) amino compound (9i) as the most potent compound with balanced dual activity (K-i(Thr) = 0.33 +/- 0.07 mu M, IC50(GP IIb/IIIa) = 1.1 +/- 0.6 mu M). (C) 2012 Elsevier Masson SAS. All rights reserved.