3,4-dihydro-2-methyl-6-nitro-3-oxo-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester | 154365-37-4

• 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: 3,4-dihydro-2-methyl-6-nitro-3-oxo-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester
• 英文别名: ethyl (3,4-dihydro-2-methyl-6-nitro-3-oxo-2H,1,4-benzoxazin-2-yl)carboxylate；ethyl 2-methyl-6-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazine-2-carboxylate；ethyl 2-methyl-6-nitro-2H-1,4-benzoxazine-3(4H)-one-2-carboxylate；2-methyl-6-nitro-3-oxo-3,4-dihydro-2H-benzo[1,4]oxazine-2-carboxylic acid ethyl ester；ethyl 2-methyl-6-nitro-3-oxo-4H-1,4-benzoxazine-2-carboxylate
• CAS: 154365-37-4
• 化学式: C₁₂H₁₂N₂O₆
• 分子量: 280.237
• InChiKey: RARDOKXXQXTSKH-UHFFFAOYSA-N

物化性质

• 熔点：
  175-177 °C
• 沸点：
  454.5±45.0 °C(Predicted)
• 密度：
  1.372±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  110
• 氢给体数：
  1
• 氢受体数：
  6

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-2-methyl-6-nitro-3-oxo-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester 在 palladium on activated charcoal 氢气 、 sodium hydride 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 甲苯 为溶剂， -10.0~100.0 ℃ 、101.33 kPa 条件下， 反应 6.0h， 生成 ethyl 4-benzyl-6-[(4-cyanobenzoyl)amino]-2-methyl-2H-1,4-benzoxazin-3(4H)-one-2-carboxylate
  参考文献：
  名称：

  2H-1,4-苯并恶嗪-3（4H）-一个支架的新型血小板纤维蛋白原受体拮抗剂的设计与合成。有系统的研究。

  摘要：

  在2H-1,4-苯并恶嗪-3（4H）-一个支架上制备了新的血小板糖蛋白IIb / IIIa（GP IIb / IIIa，整联蛋白alpha（IIb）beta3）拮抗剂。评估了它们在富含人血小板的血浆中的抗聚集活性以及它们对alpha（IIb）beta3和alpha（V）beta3整联蛋白的亲和力。研究了各种取代位置和侧链变化。与普遍接受的模型相反，含有乙酯作为天冬氨酸盐模拟物的化合物通常比相应的游离酸更具活性。我们建议对这些新化合物的观察行为进行解释。

  DOI：

  10.1016/j.ejmech.2004.09.004
• 作为产物：
  描述：

  2-溴-2-甲基丙二酸二乙酯 、 2-氨基-4-硝基苯酚 在 potassium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 以79%的产率得到3,4-dihydro-2-methyl-6-nitro-3-oxo-2H-1,4-benzoxazine-2-carboxylic acid ethyl ester
  参考文献：
  名称：

  Novel Potassium Channel Activators. III. Synthesis and Pharmacological Evaluation of 3,4-Dihydro-2H-1,4-benzoxazine Derivatives: Modification at the 2 Position.

  摘要：

  我们合成了一系列新的 3，4-二氢-2H-1，4-苯并恶嗪衍生物，并对它们的钾离子通道激活活性进行了评估。与母体化合物 1 相比，引入羟基（如化合物 5）可获得良好的水溶性和较长的作用持续时间。 引入硝基（如化合物 8）除了可产生钾通道激活活性外，还可产生典型的硝酸盐活性，如硝化甘油所表现的活性。化合物 5 的 X 射线结构分析表明，4 位 N 原子周围的键角总和为 357.8°，表明 N 原子具有近似 sp2 的平面键构型。

  DOI：

  10.1248/cpb.48.428

文献信息

• 4-Piperidinecarboxamide modulators of vanilloid VR1 receptor
  申请人：Calvo R. Raul

  公开号：US20060116368A1

  公开（公告）日：2006-06-01

  This invention is directed to vanilloid receptor VR1 ligands. More particularly, this invention relates to hetero isonipecotic amides that are potent modulators of VR1 which are useful for the treatment and prevention of disease conditions in mammals.

  这项发明涉及辣椒素受体VR1配体。更具体地说，这项发明涉及对VR1具有潜在调节作用的杂环异尼泊酸酰胺，这些化合物对于治疗和预防哺乳动物的疾病状况是有用的。
• A convenient synthesis of 3,4-dihydro-2-methyl-3-oxo-<i>2H</i>-1,4-benzoxazine-2-carboxylic acids and 3,4-dihydro-2-methyl-3-oxo-<i>2H</i>-pyrido[3,2-<i>b</i>]-1, 4-oxazine-2-carboxylic acid
  作者：Elizabeta Suhadolc、UroŠ Urleb、Urša Žbontar、Danijel Kikelj

  DOI：10.1002/jhet.5570300303

  日期：1993.5

  A convenient one pot synthesis of ethyl 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylates and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1,4-oxazine-2-carboxylates and their conversion into the respective carboxylic acids are described.

  一种方便的一锅合成乙基的3,4-二氢-2-甲基-3-氧代- 2H -1,4-苯并恶嗪-2-羧酸和3,4-二氢-2-甲基-3-氧代- 2H吡啶并描述了[3，2 - b ] -1，4-恶嗪-2-羧酸酯及其转化为相应的羧酸。
• Conformationally tailored N-[(2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl)carbonyl]proline templates as molecular tools for the design of peptidomimetics. Design and synthesis of fibrinogen receptor antagonists
  作者：Petra Štefanič、Zvone Simončič、Matej Breznik、Janez Plavec、Marko Anderluh、Elisabeth Addicks、Athanassios Giannis、Danijel Kikelj

  DOI：10.1039/b400490f

  日期：——

  The proline peptide bond was shown by 2D proton NMR studies to exist exclusively in the trans conformation in benzyl (2S)-1-[(2S)-2-methyl-6-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl}-2-pyrrolidinecarboxylate [(S,S)-11], benzyl (2S)-1-[(2S)-2-methyl-7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl}-2-pyrrolidinecarboxylate [(S,S)-9], and in the corresponding 6-amino and 7-amino carboxylic acids (S,S)-3 and (S,S)-4. On the other hand, the diastereomers (R,S)-11 and (R,S)-9 containing an (R) [2-methyl-6/7-nitro-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety, and the diastereoisomers (R,S)-3 and (R,S)-4 incorporating an (R) [6/7-amino-2-methyl-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-2-yl]carbonyl moiety were found to exist as equilibria of trans (63–83%) and cis (17–37%) isomers. These conformationally defined templates were applied in the construction of RGD mimetics possessing antagonistic activity at the platelet fibrinogen receptor.

  二维质子核磁共振研究表明，在(2S)-1-[(2S)-2-甲基-6-硝基-3-氧代-3,4-二氢-2H-1,4-苯并恶嗪-2-基]羰基}-2-吡咯烷羧酸苄酯[(S.S)-11]中，脯氨酸肽键完全以反式构象存在、(S,S)-11]、(2S)-1-[(2S)-2-甲基-7-硝基-3-氧代-3,4-二氢-2H-1,4-苯并恶嗪-2-基]羰基}-2-吡咯烷羧酸苄酯[(S,S)-9]，以及相应的 6-氨基和 7-氨基羧酸 (S,S)-3 和 (S,S)-4。另一方面，非对映异构体 (R,S)-11 和 (R,S)-9 含有一个 (R) [2-甲基-6/7-硝基-3-氧代-3,4-二氢-2H-1,4-苯并恶嗪-2-基]羰基，非对映异构体 (R,S)-3 和 (R、S)-4 包含一个 (R) [6/7-氨基-2-甲基-3-氧代-3,4-二氢-2H-1,4-苯并恶嗪-2-基]羰基，它们以反式（63-83%）和顺式（17-37%）异构体的平衡形式存在。这些构象明确的模板被用于构建对血小板纤维蛋白原受体具有拮抗活性的 RGD 拟效物。
• 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.