7-methoxy-4-(3-phenylpiperidin-1-yl)-6-(2-pyridin-4-ylethoxy)quinazoline | 1311509-46-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 7-methoxy-4-(3-phenylpiperidin-1-yl)-6-(2-pyridin-4-ylethoxy)quinazoline
• CAS: 1311509-46-2
• 化学式: C₂₇H₂₈N₄O₂
• 分子量: 440.545
• InChiKey: HGHZWVNQYHVSEI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  33
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  60.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-苯基哌啶 在 甲烷磺酸 、 L-蛋氨酸 、 偶氮二甲酸二叔丁酯 、 N,N-二异丙基乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 异丙醇 为溶剂， 反应 10.0h， 生成 7-methoxy-4-(3-phenylpiperidin-1-yl)-6-(2-pyridin-4-ylethoxy)quinazoline
  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.