2-(Dimethylamino)-1-(6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone | 793672-21-6

• 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-(Dimethylamino)-1-(6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone
• CAS: 793672-21-6
• 化学式: C₁₃H₁₈N₂O₃
• 分子量: 250.298
• InChiKey: PLXROYCYNKWSPV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  42
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(Dimethylamino)-1-(6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone 在 lithium aluminium tetrahydride 、 三氯化铝 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 4.0h， 以47%的产率得到[2-(6-methoxy-2,3-dihydrobenzo[1,4]oxazin-4-yl)ethyl]dimethylamine
  参考文献：
  名称：

  Novel 5-HT₇ Receptor Inverse Agonists. Synthesis and Molecular Modeling of Arylpiperazine- and 1,2,3,4-Tetrahydroisoquinoline-Based Arylsulfonamides

  摘要：

  A series of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides was synthesized and evaluated for their interactions with the constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced a decrease of adenylate cyclase activity, indicative of their inverse agonism. Additionally, computational studies with a set of 22 inverse agonists, including these novel inverse agonists and inverse agonists known from literature, resulted in a pharmacophore model and a CoMFA model (R-2 = 0.97, SE = 0.18). Docking of inverse agonists at the binding site of a model of the helical parts of the 5-HT7 receptor, based on the a carbon template for 7-TM GPCRs, revealed interesting molecular interactions and a possible explanation for observed structure-activity relationships.

  DOI：

  10.1021/jm049743b
• 作为产物：
  描述：

  4-甲氧基-2-硝基酚 在 palladium on activated charcoal 吡啶 、 lithium aluminium tetrahydride 、 氢气 、 potassium carbonate 、 potassium iodide 作用下， 以 四氢呋喃 、 乙醇 、 乙腈 为溶剂， 20.0 ℃ 、241.32 kPa 条件下， 反应 22.33h， 生成 2-(Dimethylamino)-1-(6-methoxy-2,3-dihydro-1,4-benzoxazin-4-yl)ethanone
  参考文献：
  名称：

  Novel 5-HT₇ Receptor Inverse Agonists. Synthesis and Molecular Modeling of Arylpiperazine- and 1,2,3,4-Tetrahydroisoquinoline-Based Arylsulfonamides

  摘要：

  A series of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides was synthesized and evaluated for their interactions with the constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced a decrease of adenylate cyclase activity, indicative of their inverse agonism. Additionally, computational studies with a set of 22 inverse agonists, including these novel inverse agonists and inverse agonists known from literature, resulted in a pharmacophore model and a CoMFA model (R-2 = 0.97, SE = 0.18). Docking of inverse agonists at the binding site of a model of the helical parts of the 5-HT7 receptor, based on the a carbon template for 7-TM GPCRs, revealed interesting molecular interactions and a possible explanation for observed structure-activity relationships.

  DOI：

  10.1021/jm049743b

文献信息

• Novel 5-HT₇ Receptor Inverse Agonists. Synthesis and Molecular Modeling of Arylpiperazine- and 1,2,3,4-Tetrahydroisoquinoline-Based Arylsulfonamides
  作者：Erik S. Vermeulen、Marjan van Smeden、Anne W. Schmidt、Jeffrey S. Sprouse、Håkan V. Wikström、Cor J. Grol

  DOI：10.1021/jm049743b

  日期：2004.10.1

  A series of arylpiperazine- and 1,2,3,4-tetrahydroisoquinoline-based arylsulfonamides was synthesized and evaluated for their interactions with the constitutively active 5-HT7 receptor. Effects on basal adenylate cyclase activity were measured using HEK-293 cells expressing the rat 5-HT7. All ligands produced a decrease of adenylate cyclase activity, indicative of their inverse agonism. Additionally, computational studies with a set of 22 inverse agonists, including these novel inverse agonists and inverse agonists known from literature, resulted in a pharmacophore model and a CoMFA model (R-2 = 0.97, SE = 0.18). Docking of inverse agonists at the binding site of a model of the helical parts of the 5-HT7 receptor, based on the a carbon template for 7-TM GPCRs, revealed interesting molecular interactions and a possible explanation for observed structure-activity relationships.