7-methoxy-4-(3-phenylpiperidin-1-yl)-6-n-propoxyquinazoline

• 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-n-propoxyquinazoline
• 英文别名: 7-Methoxy-4-(3-phenyl-piperidin-1-yl)-6-propoxy-quinazoline；7-Methoxy-4-(3-phenylpiperidin-1-yl)-6-propoxyquinazoline
• 化学式: C₂₃H₂₇N₃O₂
• 分子量: 377.486
• InChiKey: ADRRQOWUXMNGNP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  47.5
• 氢给体数：
  0
• 氢受体数：
  5

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 34.0h， 生成 7-methoxy-4-(3-phenylpiperidin-1-yl)-6-n-propoxyquinazoline
  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

• Novel piperidyl derivatives of quinazoline and isoquinoline
  申请人：Humphrey Michael John

  公开号：US20060019975A1

  公开（公告）日：2006-01-26

  The invention pertains to new piperidyl-substituted quinazoline and isoquinoline derivatives that serve as effective phosphodiesterase (PDE) inhibitors. The invention also relates to compounds that are selective inhibitors of PDE10. The invention further relates to intermediates for preparation of such compounds; pharmaceutical compositions comprising such compounds; and the use of such compounds in methods for treating certain central nervous system (CNS) or other disorders.

  本发明涉及新的哌啶基取代的喹唑啉和异喹啉衍生物，可作为有效的磷酸二酯酶（PDE）抑制剂。本发明还涉及选择性抑制剂PDE10的化合物。本发明还涉及用于制备这类化合物的中间体；包含这类化合物的药物组合物；以及利用这类化合物治疗某些中枢神经系统（CNS）或其他疾病的方法。
• QUINAZOLIN-4-YL-PIPERIDINE AND CINNOLIN-4-YL-PIPERIDINE DERIVATIVES AS PDE10 INHIBITORS FOR THE TREATMENT OF CNS DISORDERS
  申请人：Pfizer Products Incorporated

  公开号：EP1773805A1

  公开（公告）日：2007-04-18
• [EN] QUINAZOLIN-4-YL- PIPERIDINE AND CINNOLIN-4-YL- PIPERIDINE DERIVATIVES AS PDE10 INHIBITORS FOR THE TREATMENT OF CNS DISORDERS<br/>[FR] DERIVES QUINAZOLIN-4-YL- PIPERIDINE ET CINNOLIN-4-YL-PIPERIDINE UTILISES EN TANT QU'INHIBITEURS DE PDE10 POUR LE TRAITEMENT DE TROUBLES DU SNC
  申请人：PFIZER PROD INC

  公开号：WO2006011040A1

  公开（公告）日：2006-02-02

  The invention pertains to new piperidyl-substituted quinazoline and isoquínoline derivatives of formula (I) that serve as effective phosphodiesterase (PDE) inhibitors. The invention also relates to compounds that are selective inhibitors of PDE10. The invention further relates to intermediates for preparation of such compounds; pharmaceutical compositions comprising such compounds; and the use of such compounds in methods for treating certain central nervous system (CNS) or other disorders.
• 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.