dimethyl (2E)-2-[(2-fluorophenyl)amino]but-2-enedioate | 1314141-66-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: dimethyl (2E)-2-[(2-fluorophenyl)amino]but-2-enedioate
• 英文别名: dimethyl (E)-2-(2-fluoroanilino)but-2-enedioate
• CAS: 1314141-66-6
• 化学式: C₁₂H₁₂FNO₄
• 分子量: 253.23
• InChiKey: LMMCCSQJWSUBJR-JXMROGBWSA-N

物化性质

• 沸点：
  349.5±42.0 °C(Predicted)
• 密度：
  1.291±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl (2E)-2-[(2-fluorophenyl)amino]but-2-enedioate 在 1,1'-双(二苯膦基)二茂铁二氯化钯(II)二氯甲烷复合物 甲烷磺酸 、 四磷十氧化物 、 potassium carbonate 、 caesium carbonate 、 三溴氧磷 作用下， 以 四氢呋喃 、 水 、 甲苯 、 乙腈 为溶剂， 反应 8.0h， 生成 8-fluoro-4-[(6-methoxypyridin-3-yl)methyl]quinoline-2-carboxylic acid
  参考文献：
  名称：

  [EN] QUINOLINE AMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  [FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DU RÉCEPTEUR M1 À BASE DE QUINOLINAMIDE

  摘要：

  本发明涉及式(I)的喹啉酰胺化合物，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具有用处。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：

  WO2011084368A1
• 作为产物：
  描述：

  丁炔二酸二甲酯 生成 dimethyl (2E)-2-[(2-fluorophenyl)amino]but-2-enedioate
  参考文献：
  名称：

  DOEHNER, ROBERT F.

  摘要：

  DOI：

文献信息

• [EN] QUINOLINE CARBOXAMIDE AND QUINOLINE CARBONITRILE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE<br/>[FR] DÉRIVÉS QUINOLÉINE CARBOXAMIDES ET QUINOLÉINE CARBONITRILES EN TANT QUE MODULATEURS ALLOSTÉRIQUES NÉGATIFS DE MGLUR2, COMPOSITIONS ET LEUR UTILISATION
  申请人：MERCK SHARP & DOHME

  公开号：WO2013066736A1

  公开（公告）日：2013-05-10

  The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

  本发明提供了式(I)喹啉甲酰胺和喹啉腈化合物，其中环A，RQ，-L-，R1，n，R2和R3的定义如本文所述。本发明的化合物可用作非竞争性mGluR2拮抗剂或mGluR2负变构调节剂(NAMs)，并且用于治疗患者(最好是人类)的疾病或失调的方法，其中涉及mGluR2-NAM受体，如阿尔茨海默病，认知障碍，精神分裂症和其他情绪障碍，疼痛障碍和睡眠障碍，通过向患者投给治疗有效量的本发明化合物或其药用可接受的盐。本发明还涉及包含本发明化合物或其药用可接受的盐(可选地与一个或多个其他活性成分组合)和药用可接受载体的药物组合物，以及使用本发明的化合物和药物组合物治疗这些疾病。
• QUINOLINE AMIDE M1 RECEPTOR POSITIVE ALLOSTERIC MODULATORS
  申请人：Kuduk Scott D.

  公开号：US20120252808A1

  公开（公告）日：2012-10-04

  The present invention is directed to quinoline amide 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)的喹啉酰胺化合物，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，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，以及使用该化合物和组合物治疗M1受体介导的疾病。
• QUINOLINE CARBOXAMIDE AND QUINOLINE CARBONITRILE DERIVATIVES AS mGluR2-NEGATIVE ALLOSTERIC MODULATORS, COMPOSITIONS, AND THEIR USE
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20140309227A1

  公开（公告）日：2014-10-16

  The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, R Q , -L-, R 1 , n, R 2 , and R 3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

  本发明提供了公式（I）中环A、RQ、-L-、R1、n、R2和R3所定义的喹啉羧酰胺和喹啉羰基化合物。本发明的化合物可用作非竞争性mGluR2拮抗剂或mGluR2负向变构调节剂（NAMs），并且用于治疗患有mGluR2-NAM受体参与的疾病或障碍的患者（优选为人类），例如阿尔茨海默病、认知障碍、精神分裂症和其他情绪障碍、疼痛障碍和睡眠障碍，通过向患者投予本发明化合物或其药学上可接受的盐的治疗有效剂量。本发明还涉及包含本发明化合物或其药学上可接受的盐（可选与一种或多种其他活性成分组合）和药学上可接受的载体的制药组合物，以及本发明化合物和制药组合物在治疗此类疾病中的应用。
• Quinoline carboxamide and quinoline carbonitrile derivatives as mGluR2-negative allosteric modulators, compositions, and their use
  申请人：Merck Sharp & Dohme Corp.

  公开号：US09278960B2

  公开（公告）日：2016-03-08

  The present invention provides quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined herein. The compounds of the invention are useful as non-competitive mGluR2 antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating a patient (preferably a human) for diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders, by administering to the patient a therapeutically effective amount of a compound of the invention, or a pharmaceutically acceptable salt thereof. The invention is also directed to pharmaceutical compositions comprising a compound of the invention, or a pharmaceutically acceptable salt thereof, (optionally in combination with one or more additional active ingredients), and a pharmaceutically acceptable carrier, and the use of the compounds and pharmaceutical compositions of the invention in the treatment of such diseases.

  本发明提供了式（I）中的喹啉羧酰胺和喹啉羰基化合物，其中环A，RQ，-L-，R1，n，R2和R3如本文所定义。本发明的化合物可用作非竞争性mGluR2拮抗剂，或mGluR2负向变构调节剂（NAMs），并用于治疗患有mGluR2-NAM受体参与的疾病或疾病的患者（首选为人类），如阿尔茨海默病，认知障碍，精神分裂症和其他情绪障碍，疼痛障碍和睡眠障碍，通过向患者给予本发明化合物或其药学上可接受的盐的治疗有效量。本发明还涉及包含本发明化合物或其药学上可接受的盐（可选地与一种或多种其他活性成分结合）和药学上可接受的载体的制药组合物，以及本发明化合物和制药组合物在治疗此类疾病中的用途。
• Quinoline amide M1 receptor positive allosteric modulators
  申请人：Kuduk Scott D.

  公开号：US09199939B2

  公开（公告）日：2015-12-01

  The present invention is directed to quinoline amide 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)的喹啉酰胺化合物，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、疼痛或睡眠障碍中有用。本发明还涉及包含该化合物的药物组合物，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。