3,4-dihydro-3-propyl-2H-benzo[b][1,4]oxazine

• 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-3-propyl-2H-benzo[b][1,4]oxazine
• 英文别名: 3-propyl-3,4-dihydro-2H-benzoxazine；3-propyl-benzomorpholine；3-propyl-3,4-dihydro-2H-1,4-benzoxazine
• 化学式: C₁₁H₁₅NO
• 分子量: 177.246
• InChiKey: ZJKJZWNGHUXQAZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  21.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3,4-dihydro-3-propyl-2H-benzo[b][1,4]oxazine 在 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 23.17h， 生成 3,7-dihydro-N-(3,5-dimethyladamant-1-yl)-7-oxo-3-propyl-2H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide
  参考文献：
  名称：

  7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists

  摘要：

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.

  DOI：

  10.1021/jm300763w
• 作为产物：
  描述：

  1-cyclopropyl-2-(2-nitrophenoxy)ethanone 在 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 20.0 ℃ 、405.33 kPa 条件下， 以54%的产率得到3,4-dihydro-3-propyl-2H-benzo[b][1,4]oxazine
  参考文献：
  名称：

  7-Oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists

  摘要：

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.

  DOI：

  10.1021/jm300763w

文献信息

• 一种以苯硼酸、胺与多聚甲醛合成曼尼希碱和苯并噁嗪衍生物的方法
  申请人：华南理工大学

  公开号：CN106928163A

  公开（公告）日：2017-07-07

  本发明公开了一种以苯硼酸、胺与多聚甲醛合成曼尼希碱和苯并噁嗪衍生物的方法。该方法以苯硼酸、胺、多聚甲醛为原料，多组分、一锅合成曼尼希碱或苯并噁嗪及其衍生物。本发明以化学性质相对更稳定、更易于操作的苯硼酸替代苯酚原料，无需额外添加任何酸性物质。而且本发明为曼尼希碱和苯并噁嗪衍生物的合成提供了一条简单、产率较高、选择性好、易于实现、有价值的途径。
• HETEROCYCLIC COMPOUNDS USED AS FGFR INHIBITORS
  申请人：Nanjing InnoCare Pharma Tech Co., Ltd.

  公开号：US20190144427A1

  公开（公告）日：2019-05-16

  The present invention relates to a heterocyclic compound, a pharmaceutical composition containing the same, a preparation method thereof, and use thereof as a fibroblast growth factor receptor (FGFR) inhibitor. The compound is a heterocyclic compound as shown in Formula I, or a pharmaceutically acceptable salt, prodrug, solvent compound, polymorph, isomer or stable isotopic derivative thereof. The present invention further relates to use of the compound for the treatment or prevention of related diseases which are FGFR-mediated such as cancer, and a method for applying the compound to treat said diseases.

  本发明涉及一种杂环化合物，含有该化合物的药物组合物，其制备方法以及作为成纤维细胞生长因子受体（FGFR）抑制剂的用途。该化合物为如式I所示的杂环化合物，或其药学上可接受的盐、前药、溶剂化合物、多形、异构体或稳定同位素衍生物。本发明还涉及利用该化合物治疗或预防与FGFR介导的相关疾病，如癌症等，并将该化合物应用于治疗这些疾病的方法。
• Heterocyclic compounds used as FGFR inhibitors
  申请人：Nanjing InnoCare Pharma Tech Co., Ltd.

  公开号：US10590109B2

  公开（公告）日：2020-03-17

  The present invention relates to a heterocyclic compound, a pharmaceutical composition containing the same, a preparation method thereof, and use thereof as a fibroblast growth factor receptor (FGFR) inhibitor. The compound is a heterocyclic compound as shown in Formula I, or a pharmaceutically acceptable salt, prodrug, solvent compound, polymorph, isomer or stable isotopic derivative thereof. The present invention further relates to use of the compound for the treatment or prevention of related diseases which are FGFR-mediated such as cancer, and a method for applying the compound to treat said diseases.

  本发明涉及一种杂环化合物、含有该化合物的药物组合物、其制备方法及其作为成纤维细胞生长因子受体（FGFR）抑制剂的用途。该化合物是如式 I 所示的杂环化合物，或其药学上可接受的盐、原药、溶剂化物、多晶型物、异构体或稳定同位素衍生物。本发明进一步涉及该化合物用于治疗或预防 FGFR 介导的相关疾病（如癌症）的用途，以及应用该化合物治疗上述疾病的方法。
• US4288589A
  申请人：——

  公开号：US4288589A

  公开（公告）日：1981-09-08
• 7-Oxo-[1,4]oxazino[2,3,4-<i>ij</i>]quinoline-6-carboxamides as Selective CB₂ Cannabinoid Receptor Ligands: Structural Investigations around a Novel Class of Full Agonists
  作者：Pier Giovanni Baraldi、Giulia Saponaro、Allan R. Moorman、Romeo Romagnoli、Delia Preti、Stefania Baraldi、Emanuela Ruggiero、Katia Varani、Martina Targa、Fabrizio Vincenzi、Pier Andrea Borea、Mojgan Aghazadeh Tabrizi

  DOI：10.1021/jm300763w

  日期：2012.7.26

  Cannabinoid receptor agonists have gained attention as potential therapeutic targets of inflammatory and neuropathic pain. Here, we report the identification and optimization of a series of 7-oxo-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxamide derivatives as a novel chemotype of selective cannabinoid CB2 receptor agonists. Structural modifications led to the identification of several compounds as potent and selective cannabinoid receptor agonists (20, hCB(2) K-i = 2.5 nM, SI = 166; 21, hCB(2) K-i = 0.81 nM, SI = 383; 38, hCB(2) K-i = 15.8 nM, SI > 633; 56, hCB(2) K-i = 8.12 nM, SI > 1231; (R)-58, hCB(2) K-i = 9.24 nM, SI > 1082). The effect of a chiral center on the biological activity was also investigated, and it was found that the (R)-enantiomers exhibited greater affinity at the CB2 receptor than the (S)-enantiomers. In 3,5-cyclic adenosine monophosphate assays, the novel series behaved as agonists, exhibiting functional activity at the human CB2 receptor.