ethyl 2-(6-nitro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetate | 136544-98-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: ethyl 2-(6-nitro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetate
• 英文别名: ethyl (3,4-dihydro-6-nitro-3-oxo-2H-1,4-benzoxazin-4-yl)acetate；ethyl 2-(6-nitro-3-oxo-1,4-benzoxazin-4-yl)acetate
• CAS: 136544-98-4
• 化学式: C₁₂H₁₂N₂O₆
• 分子量: 280.237
• InChiKey: LHUGZBZCOWNWGI-UHFFFAOYSA-N

物化性质

• 熔点：
  117-119 °C(Solv: ethyl ether (60-29-7))
• 沸点：
  533.2±50.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-(6-nitro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 3.0h， 以39%的产率得到(6-nitro-3-thioxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)acetic acid ethyl ester
  参考文献：
  名称：

  Discovery of Selective and Orally Bioavailable Protein Kinase Cθ (PKCθ) Inhibitors from a Fragment Hit

  摘要：

  Protein kinase C theta (PKC theta) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKC theta inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

  DOI：

  10.1021/jm500669m
• 作为产物：
  描述：

  2-氨基-4-硝基苯酚 在 四丁基溴化铵 、 potassium carbonate 作用下， 以 丙酮 、 乙腈 为溶剂， 反应 13.0h， 生成 ethyl 2-(6-nitro-3-oxo-2H-benzo[b][1,4]oxazin-4(3H)-yl)acetate
  参考文献：
  名称：

  Discovery of Selective and Orally Bioavailable Protein Kinase Cθ (PKCθ) Inhibitors from a Fragment Hit

  摘要：

  Protein kinase C theta (PKC theta) regulates a key step in the activation of T cells. On the basis of its mechanism of action, inhibition of this kinase is hypothesized to serve as an effective therapy for autoimmune diseases such as rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and psoriasis. Herein, the discovery of a small molecule PKC theta inhibitor is described, starting from a fragment hit 1 and advancing to compound 41 through the use of structure-based drug design. Compound 41 demonstrates excellent in vitro activity, good oral pharmacokinetics, and efficacy in both an acute in vivo mechanistic model and a chronic in vivo disease model but suffers from tolerability issues upon chronic dosing.

  DOI：

  10.1021/jm500669m

文献信息

• 3,4-dihydro-2H-1,4-benzoxazine derivatives and pharmaceutical
  申请人：Yamanouchi Pharmaceutical Co., Ltd.

  公开号：US05420126A1

  公开（公告）日：1995-05-30

  Novel benzoxazine derivatives of the formula (I): ##STR1## are provided as well as their pharmaceutically acceptable salts and a method for their use as potassium channel activating agents 2-(3,4-Dihydro-2, 2-dimethyl-6-phenylsulfonyl-2H-1,4-benzoxazin-4-yl)pyridine N-oxide is illustrative of a benzoxazine derivative of formula (I). Also provided are intermediate compounds such as those of formula (II): ##STR2##

  提供了一种新颖的苯并恶唑衍生物，其化学公式为(I): ##STR1##，以及它们的药用可接受盐和一种方法，用于将它们用作激活钾通道的剂2-(3,4-二氢-2,2-二甲基-6-苯磺酰基-2H-1,4-苯并恶唑-4-基)吡啶N-氧化物是公式(I)的苯并恶唑衍生物的示例。还提供了诸如公式(II)的中间化合物:##STR2##
• Synthesis, biological activity and conformational study of 1,4-benzoxazine derivatives as potassium channel modulators
  作者：Giuseppe Caliendo、Paolo Grieco、Elisa Perissutti、Vincenzo Santagada、Antonello Santini、Stefania Albrizio、Caterina Fattorusso、Aldo Pinto、Raffaella Sorrentino

  DOI：10.1016/s0223-5234(99)80020-8

  日期：1998.12

  With the aim of discovering new molecules with K+-channel activating properties, we have synthesized derivatives of cromakalim (CRK), an important molecule which shows specific affinity towards K+ channels, by replacing the benzopyrane ring of this reference compound with a 1,4-benzoxazine moiety. A different number of substituents showing a good discrimination between hydrophobic and electronic properties have been inserted at the 6-position of the 1,4-benzoxazine ring. We describe here the synthesis and discuss the solid state conformation of these new molecules. When tested on rat aorta ring precontracted with phenylephrine, two compounds (2c and 2d) showed a concentration-dependent relaxation similar to that measured for cromakalim but less potent than this reference drug. (C) Elsevier, Paris.
• Synthesis by microwave irradiation of a substituted benzoxazine parallel library with preferential relaxant activity for guinea pig trachealis
  作者：Giuseppe Caliendo、Elisa Perissutti、Vincenzo Santagada、Ferdinando Fiorino、Beatrice Severino、Donatella Cirillo、Roberta d’Emmanuele di Villa Bianca、Laura Lippolis、Aldo Pinto、Raffaella Sorrentino

  DOI：10.1016/j.ejmech.2004.05.003

  日期：2004.10

  An efficient, facile, and practical parallel combinatorial synthesis of substituted-benzoxazines under microwave irradiation was described. The procedure involved the use of a microwave oven especially designed for organic synthesis suitable for parallel synthesis of solution libraries. A demonstration 19-membered library of substituted N,N-dimethyl- and N-methyl-benzoxazine amide derivatives, structurally related to the potassium channel opener cromakalim, was generated by both conventional and microwave procedures, achieving a reduction from 7 h to 30-36 min in library generation time for the microwave approach. All the synthesized compounds were tested using the in vitro models of rat aorta and guinea pig trachea rings pre-contracted with phenylephrine and carbachol, respectively. All N,N-dimethyl amide derivatives showed a relaxant activity higher on guinea pig trachea rings than on rat aorta rings. (C) 2004 Elsevier SAS. All rights reserved.
• WO2006/69788
  申请人：——

  公开号：——

  公开（公告）日：——
• ORGANIC COMPOUNDS
  申请人：Breitenstein Werner

  公开号：US20090312304A1

  公开（公告）日：2009-12-17

  3,4-substituted piperidine compounds, these compounds for use in the diagnostic and therapeutic treatment of a warm-blooded animal, especially for the treatment of a disease (=disorder) that depends on activity of renin; the use of a compound of that class for the preparation of a pharmaceutical formulation for the treatment of a disease that depends on activity of renin; the use of a compound of that class in the treatment of a disease that depends on activity of renin; pharmaceutical formulations comprising a 3,4-substituted piperidine compound, and/or a method of treatment comprising administering a 3,4-substituted piperidine compound, a method for the manufacture of a 3,4-substituted piperidine compound, and novel intermediates and partial steps for their synthesis are disclosed. The 3,4-disubstituted piperidine compounds have the formula I,