(2,4-dimethyl-7-nitro-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methanol | 1056737-05-3

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 英文名称: (2,4-dimethyl-7-nitro-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methanol
• CAS: 1056737-05-3
• 化学式: C₁₁H₁₄N₂O₄
• 分子量: 238.243
• InChiKey: HKBGVMKOWIZSGS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.17
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  75.84
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (2,4-dimethyl-7-nitro-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methanol 在 palladium 10% on activated carbon 、 氢气 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~110.0 ℃ 、2.5 MPa 条件下， 反应 2.0h， 生成 2-(([1,2,4]triazolo[4,3-b]pyridazin-6-yloxy)methyl)-2,4-dimethyl-3,4-dihydro-2H-1,4-benzoxazin-7-amine
  参考文献：
  名称：

  Ilic, Milos; Ilas, Janez; Liekens, Sandra, ARKIVOC, 2011, vol. 2011, # 10, p. 298 - 311

  摘要：

  DOI：
• 作为产物：
  描述：

  2-甲基-7-硝基-3-氧代-4H-1,4-苯并恶嗪-2-羧酸乙酯 在 potassium fluoride 、 dimethyl sulfide borane 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (2,4-dimethyl-7-nitro-3,4-dihydro-2H-1,4-benzoxazin-2-yl)methanol
  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

文献信息

• 3,4-Dihydro-2<i>H</i>-1,4-benzoxazine Derivatives Combining Thrombin Inhibitory and Glycoprotein IIb/IIIa Receptor Antagonistic Activity as a Novel Class of Antithrombotic Compounds with Dual Function
  作者：Janez Ilaš、Žiga Jakopin、Tina Borštnar、Mojca Stegnar、Danijel Kikelj

  DOI：10.1021/jm8003448

  日期：2008.9.25

  3,4-Dihydro-2H-1,4-benzoxazine derivatives possessing both thrombin inhibitory and glycoprotein IIb/IIIa (GPIIb/IIIa) receptor antagonistic activities were obtained by combining mimetics of the D-Phe-Pro-Arg pharmacophore of thrombin inhibitors and the Arg-Gly-Asp pharmacophor of GPIIb/IIIa receptor antagonists in the same low molecular weight peptidomimetic compound. Systematic variation of the position of substituents around the 3,4-dihydro-2H-1,4-benzoxazine nucleus, the distance between the carboxylate and amidine moieties, together with additional substituents to fill the thrombin S-2 and S-3 pockets resulted in compounds displaying submicromolar inhibition constants (K-i) for thrombin and submicromolar IC50 for inhibition of binding of fibrinogen to platelet GPIIb/IIIa receptor. Some of these compounds, such as 17a, 17b, 17d, and 17h possessing a well balanced activity at both targets, are a good starting point for further optimization. Incorporation of anticoagulant and platelet antiaggregatory activity in the same molecule constitutes a promising approach toward novel antithrombotic agents.
• 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.
• Novel 1,4-benzoxazine and 1,4-benzodioxine inhibitors of angiogenesis
  作者：Miloš Ilić、Janez Ilaš、Petra Dunkel、Péter Mátyus、Andrej Boháč、Sandra Liekens、Danijel Kikelj

  DOI：10.1016/j.ejmech.2012.10.001

  日期：2012.12

  Esters of 1,4-benzoxazine and 1,4-benzodioxine compounds 1 and 10, which combine thrombin inhibitory and GPIIb/IIIa antagonistic activity in one molecule are shown to inhibit endothelial cell migration and tube formation in vitro and angiogenesis in the chicken chorioallantoic membrane (CAM) assay. The corresponding carboxylic acids 1 (R-2 = H) and 11 were devoid of anti-angiogenic activity, most probably due to their insufficient entry into the cell. Although thrombin inhibition remains the most probable explanation for their inhibition of angiogenesis, VEGFR2 kinase assay suggest that other targets such as VEGFR2 might be involved. (C) 2012 Elsevier Masson SAS. All rights reserved.