1-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-N-(oxan-4-yl)-4-oxoquinolizine-3-carboxamide | 1309079-39-7

• 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-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-N-(oxan-4-yl)-4-oxoquinolizine-3-carboxamide
• CAS: 1309079-39-7
• 化学式: C₂₇H₂₉N₅O₃
• 分子量: 471.559
• InChiKey: JXVLBLUZXYVJPZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  98.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-氨基四氢吡喃 、 sodium 1-((4-cyano-4-(pyridin-2-yl)piperidin-1-yl)methyl)-4-oxo-4H-quinolizine-3-carboxylate 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 1.0h， 以79%的产率得到1-[(4-cyano-4-pyridin-2-ylpiperidin-1-yl)methyl]-N-(oxan-4-yl)-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

文献信息

• QUINOLIZIDINONE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Kuduk Scott D.

  公开号：US20120232076A1

  公开（公告）日：2012-09-13

  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，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M1受体介导的疾病。
• US8754220B2
  申请人：——

  公开号：US8754220B2

  公开（公告）日：2014-06-17
• [EN] QUINOLIZIDINONE CARBOXAMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE TYPE QUINOLIZIDINONE-CARBOXAMIDE
  申请人：MERCK SHARP & DOHME

  公开号：WO2011062853A1

  公开（公告）日：2011-05-26

  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.
• Identification of Amides as Carboxylic Acid Surrogates for Quinolizidinone-Based M₁ Positive Allosteric Modulators
  作者：Scott D. Kuduk、Ronald K. Chang、Thomas J. Greshock、William J. Ray、Lei Ma、Marion Wittmann、Matthew A. Seager、Kenneth A. Koeplinger、Charles D. Thompson、George D. Hartman、Mark T. Bilodeau

  DOI：10.1021/ml300280g

  日期：2012.12.13

  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.