[4-(1-methyl-2-oxopropyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetaldehyde | 876921-50-5

• 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: [4-(1-methyl-2-oxopropyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetaldehyde
• 英文别名: 2-[3-Oxo-4-(3-oxobutan-2-yl)-1,4-benzoxazin-8-yl]acetaldehyde
• CAS: 876921-50-5
• 化学式: C₁₄H₁₅NO₄
• 分子量: 261.277
• InChiKey: UAFLLCBXRSMNJV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  63.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-methyl-5-(1-piperazinyl)quinoline 、 [4-(1-methyl-2-oxopropyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetaldehyde 在 sodium (triacetoxy)borohydride 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 3.25h， 以92%的产率得到4-(1-methyl-2-oxopropyl)-8-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]-ethyl}-2H-1,4-benzoxazin-3(4H)-one
  参考文献：
  名称：

  Design and Synthesis of Novel Tricyclic Benzoxazines as Potent 5-HT_1A/B/D Receptor Antagonists Leading to the Discovery of 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045)

  摘要：

  Bioisoteric replacement of the metabolically labile N-methyl amide group of a series of benzoxazinones with small heterocyclic rings has led to novel series of fused tricyclic benzoxazines which are potent 5-HT1A/B/D receptor antagonists with and without concomitant human serotonin transporter (hSerT) activity. Optimizing against multiple parameters in parallel identified 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045) as a potent 5-HT1A/B/D receptor antagonist with a high degree of selectivity over human ether-a-go-go related gene (hERG) potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models. On the basis of its outstanding overall profile, this compound was progressed as a clinical candidate with the ultimate aim to assess its potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden.

  DOI：

  10.1021/jm100482n
• 作为产物：
  描述：

  在 sodium periodate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 2.0h， 生成 [4-(1-methyl-2-oxopropyl)-3-oxo-3,4-dihydro-2H-1,4-benzoxazin-8-yl]acetaldehyde
  参考文献：
  名称：

  Design and Synthesis of Novel Tricyclic Benzoxazines as Potent 5-HT_1A/B/D Receptor Antagonists Leading to the Discovery of 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045)

  摘要：

  Bioisoteric replacement of the metabolically labile N-methyl amide group of a series of benzoxazinones with small heterocyclic rings has led to novel series of fused tricyclic benzoxazines which are potent 5-HT1A/B/D receptor antagonists with and without concomitant human serotonin transporter (hSerT) activity. Optimizing against multiple parameters in parallel identified 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045) as a potent 5-HT1A/B/D receptor antagonist with a high degree of selectivity over human ether-a-go-go related gene (hERG) potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models. On the basis of its outstanding overall profile, this compound was progressed as a clinical candidate with the ultimate aim to assess its potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden.

  DOI：

  10.1021/jm100482n

文献信息

• FUSED TRICYCLIC DERIVATIVES FOR THE TREATMENT OF PSYCHOTIC DISORDERS
  申请人：Bentley Jonathan

  公开号：US20120022056A1

  公开（公告）日：2012-01-26

  Compounds of formula (I) wherein R 1 , R 2 , X, A, Y, B, Z 1 , Q, p, r and s are defined in the specification for treating inter alia psychotic disorders, depressive disorders, anxiety disorders and sexual dysfunctions.

  式(I)中的化合物，其中R1、R2、X、A、Y、B、Z1、Q、p、r和s在规范中定义，用于治疗精神疾病、抑郁症、焦虑症和性功能障碍等疾病。
• Design and Synthesis of Novel Tricyclic Benzoxazines as Potent 5-HT_1A/B/D Receptor Antagonists Leading to the Discovery of 6-{2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4<i>H</i>-imidazo[5,1-<i>c</i>][1,4]benzoxazine-3-carboxamide (GSK588045)
  作者：Steven M. Bromidge、Roberto Arban、Barbara Bertani、Silvia Bison、Manuela Borriello、Paolo Cavanni、Giovanna Dal Forno、Romano Di-Fabio、Daniele Donati、Stefano Fontana、Massimo Gianotti、Laurie J. Gordon、Enrica Granci、Colin P. Leslie、Luca Moccia、Alessandra Pasquarello、Ilaria Sartori、Anna Sava、Jeannette M. Watson、Angela Worby、Laura Zonzini、Valeria Zucchelli

  DOI：10.1021/jm100482n

  日期：2010.8.12

  Bioisoteric replacement of the metabolically labile N-methyl amide group of a series of benzoxazinones with small heterocyclic rings has led to novel series of fused tricyclic benzoxazines which are potent 5-HT1A/B/D receptor antagonists with and without concomitant human serotonin transporter (hSerT) activity. Optimizing against multiple parameters in parallel identified 6-2-[4-(2-methyl-5-quinolinyl)-1-piperazinyl]ethyl}-4H-imidazo[5,1-c][1,4]benzoxazine-3-carboxamide (GSK588045) as a potent 5-HT1A/B/D receptor antagonist with a high degree of selectivity over human ether-a-go-go related gene (hERG) potassium channels, favorable pharmacokinetics, and excellent activity in vivo in rodent pharmacodynamic (PD) models. On the basis of its outstanding overall profile, this compound was progressed as a clinical candidate with the ultimate aim to assess its potential as a faster acting antidepressant/anxiolytic with reduced side-effect burden.