6-(benzyloxy)-7-methoxy-3-methylquinazolin-4(3H)-one | 1311509-51-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 6-(benzyloxy)-7-methoxy-3-methylquinazolin-4(3H)-one
• 英文别名: 7-Methoxy-3-methyl-6-phenylmethoxyquinazolin-4-one
• CAS: 1311509-51-9
• 化学式: C₁₇H₁₆N₂O₃
• 分子量: 296.326
• InChiKey: IWEVRWYVWGSWGA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  51.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(benzyloxy)-7-methoxy-3-methylquinazolin-4(3H)-one 在 苯甲醚 作用下， 以 三氟乙酸 为溶剂， 以95%的产率得到6-hydroxy-7-methoxy-3-methylquinazolin-4(3H)-one
  参考文献：
  名称：

  Use of Structure-Based Design to Discover a Potent, Selective, In Vivo Active Phosphodiesterase 10A Inhibitor Lead Series for the Treatment of Schizophrenia

  摘要：

  Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.

  DOI：

  10.1021/jm2001508
• 作为产物：
  描述：

  2-氨基-5-(苄氧基)-4-甲氧基苯甲酸甲酯 在 lithium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 32.0h， 生成 6-(benzyloxy)-7-methoxy-3-methylquinazolin-4(3H)-one
  参考文献：
  名称：

  Use of Structure-Based Design to Discover a Potent, Selective, In Vivo Active Phosphodiesterase 10A Inhibitor Lead Series for the Treatment of Schizophrenia

  摘要：

  Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.

  DOI：

  10.1021/jm2001508

文献信息

• Use of Structure-Based Design to Discover a Potent, Selective, In Vivo Active Phosphodiesterase 10A Inhibitor Lead Series for the Treatment of Schizophrenia
  作者：Christopher J. Helal、Zhijun Kang、Xinjun Hou、Jayvardhan Pandit、Thomas A. Chappie、John M. Humphrey、Eric S. Marr、Kimberly F. Fennell、Lois K. Chenard、Carol Fox、Christopher J. Schmidt、Robert D. Williams、Douglas S. Chapin、Judith Siuciak、Lorraine Lebel、Frank Menniti、Julia Cianfrogna、Kari R. Fonseca、Frederick R. Nelson、Rebecca O’Connor、Mary MacDougall、Laura McDowell、Spiros Liras

  DOI：10.1021/jm2001508

  日期：2011.7.14

  Utilizing structure-based virtual library design and scoring, a novel chimeric series of phosphodiesterase 10A (PDE10A) inhibitors was discovered by synergizing binding site interactions and ADME properties of two chemotypes. Virtual libraries were docked and scored for potential binding ability, followed by visual inspection to prioritize analogs for parallel and directed synthesis. The process yielded highly potent and selective compounds such as 16. New X-ray cocrystal structures enabled rational design of substituents that resulted in the successful optimization of physical properties to produce in vivo activity and to modulate microsomal clearance and permeability.