7-methoxy-4-(pyridin-3-yl)quinazolin-6-ol | 1006889-97-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 7-methoxy-4-(pyridin-3-yl)quinazolin-6-ol
• 英文别名: 7-Methoxy-4-pyridin-3-ylquinazolin-6-ol
• CAS: 1006889-97-9
• 化学式: C₁₄H₁₁N₃O₂
• 分子量: 253.26
• InChiKey: SXXOTFTYLNCDBV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  68.1
• 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 、 7-methoxy-4-(pyridin-3-yl)quinazolin-6-ol 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63%的产率得到7-甲氧基-4-(吡啶-3-基)-6-[2-(喹啉-2-基)乙氧基]喹唑啉
  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 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 、 caesium carbonate 、 苯甲醚 、 三氯氧磷 、 三环己基膦 作用下， 以 1,4-二氧六环 、 三氟乙酸 为溶剂， 反应 51.0h， 生成 7-methoxy-4-(pyridin-3-yl)quinazolin-6-ol
  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

• [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.