1-(4-chlorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid | 1221278-93-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(4-chlorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid
• 英文别名: 1-[(4-chlorophenyl)methyl]-4-oxoquinolizine-3-carboxylic acid
• CAS: 1221278-93-8
• 化学式: C₁₇H₁₂ClNO₃
• 分子量: 313.74
• InChiKey: AOVHQAMMMJLIHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1-(4-chlorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid 、 2-吡啶硼酸 在 二(三叔丁基膦)钯 、 caesium carbonate 作用下， 以 四氢呋喃 为溶剂， 生成 4-Oxo-1-[[4-(2-pyridinyl)phenyl]methyl]-4H-quinolizine-3-carboxylic acid
  参考文献：
  名称：

  Quinolizidinone Carboxylic Acids as CNS Penetrant, Selective M₁ Allosteric Muscarinic Receptor Modulators

  摘要：

  Positive allosteric modulation of the M, muscarinic receptor represents an approach to treat the cognitive decline in patients with Alzheimer's disease. Replacement of a quinolone ring system in a quinolone carboxylic acid series of M, modulators with a quinolizidinone bearing a basic amine linkage led to a series of compounds with higher free fraction, enhanced CNS exposure, and improved efficacy in rodent in vivo models of cognition.

  DOI：

  10.1021/ml100095k
• 作为产物：
  描述：

  1-[(4-chlorophenyl)(hydroxy)methyl]-4-oxo-4H-quinolizine-3-carboxylic acid 在 三乙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 1-(4-chlorobenzyl)-4-oxo-4H-quinolizine-3-carboxylic acid
  参考文献：
  名称：

  [EN] QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  [FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE LA QUINOLIZIDINONE

  摘要：

  本发明涉及公式（I）的喹啉脲类化合物，其为M1受体正向变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍方面有用。本发明还涉及包含该化合物的制药组合物，以及使用该化合物和组合物治疗由M1受体介导的疾病。

  公开号：

  WO2010042347A1

文献信息

• [EN] QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE LA QUINOLIZIDINONE
  申请人：MERCK SHARP & DOHME

  公开号：WO2010042347A1

  公开（公告）日：2010-04-15

  The present invention is directed to quinolizidinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及公式（I）的喹啉脲类化合物，其为M1受体正向变构调节剂，并且在治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍方面有用。本发明还涉及包含该化合物的制药组合物，以及使用该化合物和组合物治疗由M1受体介导的疾病。
• Quinolizidinone M1 Receptor Positive Allosteric Modulators
  申请人：Kuduk Scott D.

  公开号：US20110178122A1

  公开（公告）日：2011-07-21

  The present invention is directed to quinolizidinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及公式(I)的喹诺利啶酮化合物，它们是M1受体正向变构调节剂，可用于治疗M1受体参与的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。本发明还涉及包含该化合物的药物组合物，以及使用该化合物和组合物治疗M1受体介导的疾病的方法。
• Quinolizidinone M1 receptor positive allosteric modulators
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08278453B2

  公开（公告）日：2012-10-02

  The present invention is directed to quinolizidinone compounds of formula (I) which are M1 receptor positive allosteric modulators and that are useful in the treatment of diseases in which the M1 receptor is involved, such as Alzheimer's disease, schizophrenia, pain or sleep disorders. The invention is also directed to pharmaceutical compositions comprising the compounds, and to the use of the compounds and compositions in the treatment of diseases mediated by the M1 receptor.

  本发明涉及公式（I）的喹诺啉酮化合物，这些化合物是M1受体正向变构调节剂，可用于治疗M1受体参与的疾病，例如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。本发明还涉及包含这些化合物的制药组合物，以及将这些化合物和组合物用于治疗由M1受体介导的疾病的用途。
• QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Merck Sharp & Dohme Corp.

  公开号：EP2340247B1

  公开（公告）日：2013-12-04
• US8278453B2
  申请人：——

  公开号：US8278453B2

  公开（公告）日：2012-10-02