1-benzoyl-4-oxo-4H-quinolizine-3-carboxylic acid

• 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-benzoyl-4-oxo-4H-quinolizine-3-carboxylic acid
• 英文别名: 1-benzoyl-4H-quinolizin-4-one-3-carboxylic acid；1-benzoyl-4-oxoquinolizine-3-carboxylic acid
• 化学式: C₁₇H₁₁NO₄
• 分子量: 293.279
• InChiKey: PHTAKDLMOHLRLP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  74.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-benzoyl-4-oxo-4H-quinolizine-3-carboxylic acid ethyl ester 在 乙醇 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 生成 1-benzoyl-4-oxo-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

文献信息

• Quinolizinone compounds and pharmaceutical composition comprising the
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04650804A1

  公开（公告）日：1987-03-17

  The invention relates to novel quinolizinone compounds having inhibitory activity on allergies and ulcers, of the formula: ##STR1## wherein R.sup.1 is tetrazolylcarbamoyl; R.sup.7 is hydrogen or aryl selected from phenyl, tolyl, xylyl, cumenyl, naphthyl and biphenylyl; R.sup.2 is hydrogen, hydroxy, lower alkyl or lower alkoxy; R.sup.3 is hydrogen, hydroxy, lower alkyl, lower alkoxy, lower alkenyloxy, phenyl, napthyl, biphenylyl, phenyl having one or more substituent(s) selected from halogen, lower alkyl and lower alkoxy, arylthio selected from phenylthio, tolylthio, xylylthio, cumenylthio, naphthylthio and biphenylthio, aroyl selected from benzoyl, toluoyl and naphthoyl, ar(lower)alkyl selected from phenyl(lower)alkyl, tolyl(lower)alkyl, xylyl(lower)alkyl, cumenyl(lower)alkyl, naphthyl(lower)alkyl and biphenylyl(lower)alkyl, arenesulfonyl selected from benzenesulfonyl and p-toluenesulfonyl, arylamino selected from phenylamino, naphthylamino, biphenylylamino, phenylamino having lower alkyl on the nitrogen atom or aryloxy selected from phenoxy and tolyloxy; or pharmaceutically acceptable salts thereof.

  该发明涉及一种具有对过敏和溃疡具有抑制活性的新型喹诺利酮化合物，其化学式为：其中R.sup.1为四唑基甲酰基；R.sup.7为氢或苯基，所述苯基选自苯基、甲苯基、二甲苯基、辛基、萘基和联苯基；R.sup.2为氢、羟基、低碳基或低烷氧基；R.sup.3为氢、羟基、低碳基、低烷氧基、低烯烷氧基、苯基、萘基、联苯基、苯基具有一个或多个取代基所选自卤素、低烷基和低烷氧基、芳基硫基所选自苯硫基、甲苯硫基、二甲苯硫基、辛基硫基、萘硫基和联苯硫基、芳酰基所选自苯甲酰基、甲苯甲酰基和萘甲酰基、芳基烷基所选自苯基烷基、甲苯基烷基、二甲苯基烷基、辛基烷基、萘基烷基和联苯基烷基、芳基磺酰基所选自苯磺酰基和对甲苯磺酰基、芳基氨基所选自苯氨基、萘氨基、联苯基氨基、苯氨基氮原子上具有低碳基或芳氧基所选自苯氧基和甲苯氧基；或其药学上可接受的盐。
• Quinolizinone compounds, and pharmaceutical composition comprising the
  申请人：Fujisawa Pharmaceutical Co., Ltd.

  公开号：US04698349A1

  公开（公告）日：1987-10-06

  The invention relates to novel quinolizinone compounds, of inhibitory activity on allergies and ulcers, of the formula: ##STR1## wherein R.sup.1 is carboxy, carbamoyl Y.sup.1, phenylcarbamoyl which may have hydroxy, cyano or thiocarbamoyl, R.sup.7 is hydrogen or aryl selected from phenyl, tolyl, xylyl, cumenyl, naphthyl and biphenylyl; R.sup.2 is hydrogen, hydroxy, lower alkyl or lower alkoxy; and R.sup.3 is hydrogen, hydroxy, lower alkyl, lower alkoxy, lower alkenyloxy, phenyl, naphthyl, biphenylyl, phenyl having one or more substituent(s) selected from halogen, lower alkyl and lower alkoxy, arylthio selected from phenylthio, tolylthio, xylylthio, cumenylthio, naphthylthio and biphenylylthio, aroyl selected from benzoyl, toluoyl and naphthoyl, ar(lower)alkyl selected from phenyl(lower)alkyl, tolyl(lower)alkyl, xylyl(lower)alkyl, cumenyl(lower)alkyl, naphthyl(lower)alkyl and biphenylyl(lower)alkyl, arenesulfonyl selected from benzenesulfonyl and p-toluenesulfonyl, arylamino selected from phenylamino, naphthylamino, biphenylylamino, phenylamino having lower alkyl on the nitrogen atom or aryloxy selected from phenoxy and tolyloxy; or pharmaceutically acceptable salts thereof.

  本发明涉及一种新的喹诺啉酮化合物，具有抗过敏和抗溃疡的抑制活性，其化学式为：##STR1## 其中，R.sup.1为羧基，氨基甲酰Y.sup.1，苯基氨基甲酰，可以具有羟基、氰基或硫代氨基甲酰基；R.sup.7为氢或被选自苯基、甲苯基、二甲苯基、叔丁基苯基、萘基和联苯基的芳基；R.sup.2为氢、羟基、低碳基或低碳氧基；R.sup.3为氢、羟基、低碳基、低碳氧基、低碳烯氧基、苯基、萘基、联苯基、苯基上有一个或多个卤素、低碳基和低碳氧基的取代基、芳基硫取代基，被选自苯基硫、甲苯基硫、二甲苯基硫、叔丁基苯基硫、萘基硫和联苯基硫、芳基酰基，被选自苯甲酰基、甲苯甲酰基和萘甲酰基、芳基（低）烷基，被选自苯基（低）烷基、甲苯基（低）烷基、二甲苯基（低）烷基、叔丁基苯基（低）烷基、萘基（低）烷基和联苯基（低）烷基、芳基磺酰基，被选自苯磺酰基和对甲苯磺酰基、芳基氨基，被选自苯基氨基、萘基氨基、联苯基氨基、氮原子上带有低碳基的苯基氨基或被选自苯氧基和甲苯氧基的芳氧基；或其药学上可接受的盐。
• [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。