ethyl 3-hydroxy-4,5,7,8-tetrahydro-6H-isoxazolo-[4,5-d]azepine-6-carboxylate | 53601-35-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吖庚因类
• 英文名称: ethyl 3-hydroxy-4,5,7,8-tetrahydro-6H-isoxazolo-[4,5-d]azepine-6-carboxylate
• 英文别名: 3-oxo-2,3,4,5,7,8-hexahydro-isoxazolo[4,5-d]azepine-6-carboxylic acid ethyl ester；ethyl 3-oxo-4,5,7,8-tetrahydro-2H-isoxazolo[4,5-d]azepine-6(3H)-carboxylate；ethyl 3-oxo-4,5,7,8-tetrahydro-[1,2]oxazolo[4,5-d]azepine-6-carboxylate
• CAS: 53601-35-7
• 化学式: C₁₀H₁₄N₂O₄
• 分子量: 226.232
• InChiKey: NPQFAUWVMJOSPB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  67.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 3-hydroxy-4,5,7,8-tetrahydro-6H-isoxazolo-[4,5-d]azepine-6-carboxylate 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 N,N-二异丙基乙胺 、 potassium bromide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 12.0h， 生成 ethyl 3-(3-fluorophenyl)-4,5,7,8-tetrahydro-6H-isoxazolo[3,4-d]azepine-6-carboxylate
  参考文献：
  名称：

  Discovery of β-Arrestin Biased Ligands of 5-HT₇R

  摘要：

  Though many studies have been published about therapeutic potentials of selective 5-HT7R ligands, there have been few biased ligands of 5-HT7R. The development of potent and selective biased ligands of 5-HT7R would be of great help in understanding the relationship between pharmacological effects and G protein/beta-arrestin signaling pathways of 5-HT7R. In order to identify 5-HT7R ligands with biased agonism, we designed and synthesized a series of tetrahydroazepine derivatives 1 and 2 with arylpyrazolo moiety or arylisoxazolo moiety. Through several biological evaluations such as binding affinity, selectivity profile, and functions in G protein and beta-arrestin signaling pathways, 3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine 1g was discovered as the beta-arrestin biased ligand of 5-HT7R. In an electroencephalogram (EEG) test, 1g increased total non-rapid eye movement (NREM) sleep time and decreased total rapid eye movement (REM) sleep time.

  DOI：

  10.1021/acs.jmedchem.8b00642
• 作为产物：
  描述：

  diethyl 1,4-dioxa-8-azaspiro[4.6]undecane-8,11-dicarboxylate 在 盐酸 、 氢氧化钾 、 羟胺 作用下， 以 甲醇 为溶剂， 生成 ethyl 3-hydroxy-4,5,7,8-tetrahydro-6H-isoxazolo-[4,5-d]azepine-6-carboxylate
  参考文献：
  名称：

  Krogsgaard-Larsen; Hjeds, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1974, vol. 28, # 5, p. 533 - 538

  摘要：

  DOI：

文献信息

• Krogsgaard-Larsen; Hjeds, Acta chemica Scandinavica. Series B: Organic chemistry and biochemistry, 1974, vol. 28, # 5, p. 533 - 538
  作者：Krogsgaard-Larsen、Hjeds

  DOI：——

  日期：——
• Discovery of β-Arrestin Biased Ligands of 5-HT₇R
  作者：Youngjae Kim、Hyunguk Kim、Jieon Lee、Jae Kyun Lee、Sun-Joon Min、Jihye Seong、Hyewhon Rhim、Jinsung Tae、Hyunjoo Jenny Lee、Hyunah Choo

  DOI：10.1021/acs.jmedchem.8b00642

  日期：2018.8.23

  Though many studies have been published about therapeutic potentials of selective 5-HT7R ligands, there have been few biased ligands of 5-HT7R. The development of potent and selective biased ligands of 5-HT7R would be of great help in understanding the relationship between pharmacological effects and G protein/beta-arrestin signaling pathways of 5-HT7R. In order to identify 5-HT7R ligands with biased agonism, we designed and synthesized a series of tetrahydroazepine derivatives 1 and 2 with arylpyrazolo moiety or arylisoxazolo moiety. Through several biological evaluations such as binding affinity, selectivity profile, and functions in G protein and beta-arrestin signaling pathways, 3-(4-chlorophenyl)-1,4,5,6,7,8-hexahydropyrazolo[3,4-d]azepine 1g was discovered as the beta-arrestin biased ligand of 5-HT7R. In an electroencephalogram (EEG) test, 1g increased total non-rapid eye movement (NREM) sleep time and decreased total rapid eye movement (REM) sleep time.