ethyl 4-oxo-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-1,4-dihydrocinnoline-3-carboxylate | 1240912-01-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 4-oxo-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-1,4-dihydrocinnoline-3-carboxylate
• 英文别名: ethyl 4-oxo-1-[4-(1H-pyrazol-1-yl)benzyl]-1,4-dihydrocinnoline-3-carboxylate；ethyl 4-oxo-1-[(4-pyrazol-1-ylphenyl)methyl]cinnoline-3-carboxylate
• CAS: 1240912-01-9
• 化学式: C₂₁H₁₈N₄O₃
• 分子量: 374.399
• InChiKey: PFVHLTNJFOSKRJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  76.8
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 4-oxo-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-1,4-dihydrocinnoline-3-carboxylate 在 劳森试剂 作用下， 以 甲苯 为溶剂， 反应 1.0h， 生成 ethyl 1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-4-thioxo-1,4-dihydrocinnoline-3-carboxylate
  参考文献：
  名称：

  [EN] PYRAZOLO [4,3-c] CINNOLIN-3-ONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  [FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 DE TYPE PYRAZOLO[4,3-C]CINNOLIN-3-ONE

  摘要：

  本发明涉及式(I)的吡唑并[4,3-c]咖啉-3-酮化合物，这些化合物是M1受体阳性变构调节剂，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。该发明还涉及包含这些化合物的药物组合物，以及在治疗由M1受体介导的疾病中使用这些化合物和组合物。

  公开号：

  WO2010096338A1
• 作为产物：
  描述：

  (2-氟苯甲酰)乙酸乙酯 在 三丁基膦 、 4-乙酰氨基苯磺酰叠氮 、 silica gel 、 potassium carbonate 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 3.0h， 生成 ethyl 4-oxo-1-{[4-(1H-pyrazol-1-yl)phenyl]methyl}-1,4-dihydrocinnoline-3-carboxylate
  参考文献：
  名称：

  2,5-二取代的吡唑并[4,3-c]肉桂醇-3-

  摘要：

  本文报道了对2,5-二取代吡唑并[4,3 - c ]肉桂醇-3-酮的补充策略，提供了在2-或5-位的晚期取代基引入。用取代的肼处理现成的4-硫代锡啉酯可以在后期进入2位，而在5位引入后期取代基则通过两种不同的策略来实现：4-肼基吡唑-3-酮的烷基化，然后分子内S N Ar的闭环反应和5-（2-氟苯基）-2,4-二氢-3 H-吡唑-3-酮与芳基重氮盐的直接反应，然后环化。本文描述的策略为制备2,5-二取代的吡唑并[4,3- c]提供了实用且通用的方法] cinnolin-3-ones。

  DOI：

  10.1002/jhet.2744

文献信息

• PYRAZOLO [4,3-c] CINNOLIN-3-ONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Beshore Douglas C.

  公开号：US20110301167A1

  公开（公告）日：2011-12-08

  The present invention is directed to pyrazolo[4,3-c]cinnolin-3-one 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)的吡唑并[4,3-c]茚啉-3-酮化合物，它们是M1受体正向变构调节剂，可用于治疗M1受体介导的疾病，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，以及使用这些化合物和组合物治疗M1受体介导的疾病的方法。
• Pyrazolo [4,3-C] cinnolin-3-one M1 receptor positive allosteric modulators
  申请人：Beshore Douglas C.

  公开号：US08653079B2

  公开（公告）日：2014-02-18

  The present invention is directed to pyrazolo[4,3-c]cinnolin-3-one 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)的吡唑并[4,3-c]茚啉-3-酮化合物，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，以及在治疗M1受体介导的疾病中使用该化合物和组合物的方法。
• Pyrazolo [4,3-c] cinnolin-3-one M1 receptor positive allosteric modulators
  申请人：Beshore Douglas C.

  公开号：US08486946B2

  公开（公告）日：2013-07-16

  The present invention is directed to pyrazolo[4,3-c]cinnolin-3-one 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)的吡唑并[4,3-c]茚啉-3-酮化合物，它们是M1受体正向变构调节剂，并且在治疗与M1受体有关的疾病，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在治疗M1受体介导的疾病方面使用这些化合物和组合物。
• HETEROCYCLIC COMPOUND AND USE THEREFOR
  申请人：Takeda Pharmaceutical Company Limited

  公开号：US20150126487A1

  公开（公告）日：2015-05-07

  The present invention provides a compound having a cholinergic muscarinic M1 receptor positive allosteric modulator activity, and useful as a prophylactic or therapeutic drug for Alzheimer's disease, schizophrenia, pain, a sleep disorder and the like. The present invention relates to a compound represented by the formula (I): wherein R 1 is an optionally substituted amino group or an optionally substituted cyclic amino group, R 2 and R 3 are each independently a hydrogen atom or a substituent, X is —CH═ or —N═, and ring A is an optionally substituted 5- to 10-membered ring, or a salt thereof.

  本发明提供了一种具有胆碱能肌动蛋白M1受体正变构调节剂活性的化合物，可用作预防或治疗阿尔茨海默病、精神分裂症、疼痛、睡眠障碍等药物。本发明涉及一种由式(I)表示的化合物：其中R1是可选取代的氨基或可选取代的环状氨基，R2和R3各自独立地是氢原子或取代基，X是—CH═或—N═，环A是可选取代的5-至10-成员环，或其盐。
• PYRAZOLO [4,3-C] CINNOLIN-3-ONE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Beshore Douglas C.

  公开号：US20130102599A1

  公开（公告）日：2013-04-25

  The present invention is directed to pyrazolo[4,3-c]cinnolin-3-one 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)的吡唑并[4,3-c]茚啉-3-酮化合物，其为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方法。