4-(二甲氨基)-7-甲氧基喹唑啉-6-醇 | 1006890-18-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 4-(二甲氨基)-7-甲氧基喹唑啉-6-醇
• 英文名称: 4-(dimethylamino)-7-methoxyquinazolin-6-ol
• CAS: 1006890-18-1
• 化学式: C₁₁H₁₃N₃O₂
• 分子量: 219.243
• InChiKey: VIGBZWPBOBIULA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.5
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-(2-羟基甲基)喹啉 、 4-(二甲氨基)-7-甲氧基喹唑啉-6-醇 在 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 以32%的产率得到7-甲氧基-N,N-二甲基-6-[2-(喹啉-2-基)乙氧基]喹唑啉-4-胺
  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：

  6-苄氧基-7-甲氧基喹唑啉-4-酮 在 苯甲醚 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 异丙醇 、 三氟乙酸 为溶剂， 反应 31.0h， 生成 4-(二甲氨基)-7-甲氧基喹唑啉-6-醇
  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

• AMINOQUINAZOLINE DERIVATIVES AND THEIR SALTS AND METHODS OF USE
  申请人：SUNSHINE LAKE PHARMA CO., LTD.

  公开号：US20140228361A1

  公开（公告）日：2014-08-14

  The present invention relates to the field of medicine. Provided herein are aminoquinazoline derivatives, their salts and pharmaceutical formulations useful in modulating the protein tyrosine kinase activity, and in modulating inter- and/or intra-cellular signaling. Also provided herein are pharmaceutically acceptable compositions comprising the aminoquinazoline compounds and methods of using the compositions in the treatment of hyperproliferative disorders in mammals, especially humans.

  本发明涉及医学领域。本文提供了氨基喹唑啉衍生物，其盐和药物配方在调节蛋白酪氨酸激酶活性以及调节细胞间和/或细胞内信号传导方面具有用处。本文还提供了包含氨基喹唑啉化合物的药用可接受组合物，以及在治疗哺乳动物，特别是人类的增生性疾病中使用这些组合物的方法。
• US9181277B2
  申请人：——

  公开号：US9181277B2

  公开（公告）日：2015-11-10
• [EN] HETEROAROMATIC QUINOLINE-BASED COMPOUNDS<br/>[FR] COMPOSÉS HÉTÉRO-AROMATIQUES À BASE DE QUINOLINE
  申请人：PFIZER PROD INC

  公开号：WO2008020302A2

  公开（公告）日：2008-02-21

  [EN] The invention pertains to heteroaromatic compounds that serve as effective phosphodiesterase (PDE) inhibitors. The invention also relates to compounds which 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. The invention relates also to methods for treating neurodegenerative and psychiatric disorders, for example psychosis and disorders comprising deficient cognition as a symptom.
  [FR] La présente invention concerne des composés hétéro-aromatiques servant d'inhibiteurs efficaces de phosphodiestérase (PDE). L'invention conerne également des composés qui sont des inhibiteurs sélectifs de PDE10. L'invention concerne en outre des intermédiaires pour la préparation de tels composés, des compositions pharmaceutiques comprenant de tels composés, ainsi que l'utilisation de tels composés dans des procédés de traitement de certains troubles du système nerveux central (CNS) ou autres. L'invention concerne de plus des procédés de traitement de troubles neurodégénératifs et psychiatriques, par exemple la psychose et des troubles ayant comme symptôme un déficit de cognition.
• 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.