2,2-Dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile | 205818-52-6

• 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: 2,2-Dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile
• 英文别名: 2,2-dimethyl-3-oxo-4H-1,4-benzoxazine-6-carbonitrile
• CAS: 205818-52-6
• 化学式: C₁₁H₁₀N₂O₂
• mdl: MFCD20039828
• 分子量: 202.213
• InChiKey: KEFFHGHKFDZMSO-UHFFFAOYSA-N

物化性质

• 熔点：
  97-99 °C(Solv: ethyl ether (60-29-7); hexane (110-54-3))
• 沸点：
  381.2±42.0 °C(Predicted)
• 密度：
  1.28±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.272
• 拓扑面积：
  62.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,2-Dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile 在 sodium hydride 、 三乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 Ethyl 4-[6-(4,5-dihydro-1,3-thiazol-2-yl)-2,2-dimethyl-3-oxo-1,4-benzoxazin-4-yl]butanoate
  参考文献：
  名称：

  新的1，4-苯并恶嗪衍生物钾通道开放剂的合成及其血管舒张活性。

  摘要：

  作为寻找新的钾通道开放剂的一部分，描述了衍生自克罗马卡林的苯并吡喃骨架的新的1,4-苯并恶嗪衍生物的合成和血管舒张活性。几种新的1,4-苯并恶嗪衍生物具有明显的血管舒张活性，其总体药理行为类似于CRK（1f，1i，2d，2e，2f和2i）。

  DOI：

  10.1016/s0968-0896(02)00091-3
• 作为产物：
  描述：

  2-bromo-N-(5-cyano-2-hydroxyphenyl)-2-methylpropanamide 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 2,2-Dimethyl-3-oxo-3,4-dihydro-2H-benzo[b][1,4]oxazine-6-carbonitrile
  参考文献：
  名称：

  新的1，4-苯并恶嗪衍生物钾通道开放剂的合成及其血管舒张活性。

  摘要：

  作为寻找新的钾通道开放剂的一部分，描述了衍生自克罗马卡林的苯并吡喃骨架的新的1,4-苯并恶嗪衍生物的合成和血管舒张活性。几种新的1,4-苯并恶嗪衍生物具有明显的血管舒张活性，其总体药理行为类似于CRK（1f，1i，2d，2e，2f和2i）。

  DOI：

  10.1016/s0968-0896(02)00091-3

文献信息

• [EN] TRICYCLIC DERIVATIVE, PREPARATION METHOD THEREFOR, AND USE THEREOF<br/>[FR] DÉRIVÉ TRICYCLIQUE, SON PROCÉDÉ DE PRÉPARATION ET SON UTILISATION<br/>[ZH] 三环类衍生物及其制备方法和用途
  申请人：[en]ZHEJIANG HISUN PHARMACEUTICAL CO., LTD.;[zh]浙江海正药业股份有限公司

  公开号：WO2023165438A1

  公开（公告）日：2023-09-07

  本发明涉及一种取代的三环类衍生物、其制备方法及含有该衍生物的药物组合物在医药上的应用。具体而言，本发明涉及一种通式(I)所示的取代的三环类衍生物、其制备方法及其可药用的盐，以及它们作为治疗剂，特别是SOS1抑制剂的用途，其中通式(I)中的各取代基的定义与说明书中的定义相同。
• 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.
• Heterobicyclic metalloprotease inhibitors
  申请人：Steeneck Christoph

  公开号：US20070155738A1

  公开（公告）日：2007-07-05

  The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic MMP-13 inhibiting and MMP-3 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP-13 and MMP-3 inhibitors.
• Heterobicyclic Metalloprotease Inhibitors
  申请人：STEENECK Christoph

  公开号：US20090312312A1

  公开（公告）日：2009-12-17

  The present invention relates generally to amide group containing pharmaceutical agents, and in particular, to amide containing heterobicyclic metalloprotease inhibitor compounds. More particularly, the present invention provides a new class of heterobicyclic MMP-13 inhibiting and MMP-3 inhibiting compounds, that exhibit an increased potency in relation to currently known MMP-13 and MMP-3 inhibitors.