1-formyl-4-oxo-4H-quinolizine-3-carboxylic acid | 1174207-59-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹嗪类
• 英文名称: 1-formyl-4-oxo-4H-quinolizine-3-carboxylic acid
• 英文别名: 1-formyl-4-oxoquinolizine-3-carboxylic acid
• CAS: 1174207-59-0
• 化学式: C₁₁H₇NO₄
• 分子量: 217.181
• InChiKey: TUTSHDCHXDOPIP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-formyl-4-oxo-4H-quinolizine-3-carboxylic acid 在 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-[(1S,2S)-2-hydroxycyclohexyl]-1-[[4-(5-methylpyridin-2-yl)piperazin-1-yl]methyl]-4-oxoquinolizine-3-carboxamide
  参考文献：
  名称：

  Identification of Amides as Carboxylic Acid Surrogates for Quinolizidinone-Based M₁ Positive Allosteric Modulators

  摘要：

  Selective activation of the M-1 muscarinic receptor via positive allosteric modulation represents an approach to treat the cognitive decline in patients with Alzheimer's disease. A series of amides were examined as a replacement for the carboxylic acid moiety in a class of quinolizidinone carboxylic acid M-1 muscarinic receptor positive allosteric modulators, and leading pyran 4o and cyclohexane 5c were found to possess good potency and in vivo efficacy.

  DOI：

  10.1021/ml300280g
• 作为产物：
  描述：

  1-甲酰基-4-氧代-4H-羟基喹啉-3-羧酸乙酯 在 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 2.0h， 以100%的产率得到1-formyl-4-oxo-4H-quinolizine-3-carboxylic acid
  参考文献：
  名称：

  荧光活化的探针的胞内镁成像2+  †

  摘要：

  描述了一种可活化的BODIPY探针，可用于游离Mg 2+的体外检测和荧光细胞成像，而不受Ca 2+的干扰。在检测到生理浓度的Mg 2+时，由于荧光团的旋转减少和基于喹oli嗪的核心的有效螯合，观察到了探针的荧光放大。

  DOI：

  10.1039/c7ob02965a

文献信息

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

  公开号：WO2009094279A1

  公开（公告）日：2009-07-30

  The present invention is directed to 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.

  本发明涉及化合物(I)的公式，这些化合物是M1受体阳性变构调节剂，可用于治疗涉及M1受体的疾病，如阿尔茨海默病、精神分裂症、疼痛或睡眠障碍。本发明还涉及包含这些化合物的药物组合物，以及这些化合物和组合物在治疗由M1受体介导的疾病中的用途。
• [EN] QUINOLIZIDINONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE QUINOLIZIDINONE
  申请人：MERCK & CO INC

  公开号：WO2009102574A1

  公开（公告）日：2009-08-20

  The present invention is directed to compounds of formula (I) (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.

  本发明涉及式(I)的化合物，它们是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，以及在治疗M1受体介导的疾病中使用该化合物和组合物的用途。
• Quinolizidinone M1 Receptor Positive Allosteric Modulators
  申请人：Kuduk Scott D.

  公开号：US20110046145A1

  公开（公告）日：2011-02-24

  The present invention is directed to 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.

  本发明涉及式(I)的化合物，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具有用途。本发明还涉及包含该化合物的制药组合物，以及在治疗由M1受体介导的疾病中使用该化合物和组合物。
• Quinolizidinone M1 receptor positive allosteric modulators
  申请人：Merck Sharp & Dohme Corp.

  公开号：US08173672B2

  公开（公告）日：2012-05-08

  The present invention is directed to 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，以及在治疗M1受体介导的疾病中使用这些化合物和组合物的方法。
• Quinolizidinone m1 Receptor Positive Allosteric Modulators
  申请人：KUDUK Scott D.

  公开号：US20110112077A1

  公开（公告）日：2011-05-12

  The present invention is directed to 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)的化合物，它们是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。本发明还涉及包含这些化合物的制药组合物，以及使用这些化合物和组合物治疗由M1受体介导的疾病。