4-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-1-(2,4-difluorophenyl)-2-piperazinone | 1146411-72-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 4-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-1-(2,4-difluorophenyl)-2-piperazinone
• 英文别名: Piperazine derivative 6；4-[2-chloro-3-(trifluoromethyl)benzoyl]-1-(2,4-difluorophenyl)piperazin-2-one
• CAS: 1146411-72-4
• 化学式: C₁₈H₁₂ClF₅N₂O₂
• 分子量: 418.75
• InChiKey: VNEYCAAUOFFQMB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  1-(2,4-二氟苯基)哌嗪-2-酮 、 2-氯-3-(三氟甲基)苯甲酸 在 4-二甲氨基吡啶 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 以22.87%的产率得到4-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-1-(2,4-difluorophenyl)-2-piperazinone
  参考文献：
  名称：

  [EN] 4-BENZ0YL-1-SUBSTITUTED-PIPERAZIN-2-0NE DERIVATIVES AS P2X7 MODULATORS
  [FR] DÉRIVÉS DE 4-BENZOYL-1-SUBSTITUÉ-PIPÉRAZIN-2-ONE COMME MODULATEURS DE P2X7

  摘要：

  该发明提供了一个具有以下式（I）的化合物或其药用盐，其中：A为C1-6烷基，C3-6环烷基，-CH2-R6，-CHMe-R7，-CMe2-R7或可选择地取代的芳基；其中，当A为可选择地取代的芳基时，所述芳基可选择地取代为1至3个取代基，这些取代基可以相同或不同，选自卤素，C1-6烷基，-CF3，C1-4烷氧基，C1氟烷氧基，氰基，NR8R9；和吡啶基，其中吡啶基可选择地被一个甲基取代；R1为氯，氟，-CF3，氰基或C1-6烷基；R2、R3和R5独立地为氢，氟，氯，-CF3，氰基或C1-6烷基，使得R2、R3和R5中至少有一个不是氢；R4为氢。这些化合物和盐被认为是P2X7受体拮抗剂。该发明还提供了该化合物或盐用于制备用于治疗疼痛、炎症、类风湿关节炎、骨关节炎或神经退行性疾病的药物的用途。

  公开号：

  WO2009053459A1

文献信息

• 4-BENZOYL-1-SUBSTITUTED-PIPERAZIN-2-ONE DERIVATIVES AS P2X7 MODULATORS
  申请人：Chambers Laura Jane

  公开号：US20100311749A1

  公开（公告）日：2010-12-09

  The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof: wherein: A is C 1-6 alkyl, C 3-6 cycloalkyl, —CH 2 —R 6 , —CHMe-R 7 , —CMe 2 -R 7 , or optionally substituted aryl; wherein, when A is optionally substituted aryl, said aryl group is optionally substituted with 1 to 3 substituents, which may be the same or different, selected from the group consisting of halogen, C 1-6 alkyl, —CF 3 , C 1-4 alkoxy, C 1 fluoroalkoxy, cyano, NR 8 R 9 , and pyridyl wherein the pyridyl is optionally substituted by one methyl; R 1 is chlorine, fluorine, —CF 3 , cyano or C 1-6 alkyl; R 2 , R 3 and R 5 independently are hydrogen, fluorine, chlorine, —CF 3 , cyano or C 1-6 alkyl, such that at least one of R 2 , R 3 and R 5 is other than hydrogen; R 4 is hydrogen. These compounds and salts are thought to be P2X7 receptor antagonists. The invention also provides for the treatment of pain, inflammation, rheumatoid arthritis, osteoarthritis, or a neurodegenerative disease.

  本发明提供了式（I）的化合物或其药学上可接受的盐：其中：A是C1-6烷基，C3-6环烷基，-CH2-R6，-CHMe-R7，-CMe2-R7或可选地取代的芳基；其中，当A是可选地取代的芳基时，所述芳基基团可选地被1至3个取代基取代，所述取代基可以是相同的或不同的，选自卤素，C1-6烷基，-CF3，C1-4烷氧基，C1氟烷氧基，氰基，NR8R9和吡啶基，其中所述吡啶基可选择地被一个甲基取代；R1是氯，氟，-CF3，氰基或C1-6烷基；R2，R3和R5独立地是氢，氟，氯，-CF3，氰基或C1-6烷基，以至少其中一个R2，R3和R5不是氢；R4是氢。这些化合物和盐被认为是P2X7受体拮抗剂。本发明还提供了治疗疼痛，炎症，类风湿性关节炎，骨关节炎或神经退行性疾病的方法。
• Methods of modulating immune activity
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US11376272B2

  公开（公告）日：2022-07-05

  In one aspect, the invention provides methods of increasing immune response by administering postcellular signaling factors produced by cells exposed to a stress condition. In one aspect, the invention provides methods of increasing immune response by administering in combination (a) a Stimulator of Interferon Genes (STING) agonist and (b) a purinergic receptor agonist. The increase in immune response may be used, for example, for treatment of infection or cancer. The invention also provides screening assays for identification of compounds that induce production of postcellular signaling factors which are also immunostimulatory agents. The invention further provides methods for identifying postcellular signaling factors with immunostimulatory activity. In another aspect, the invention provides methods of decreasing immune response by administering to a cell, tissue or subject a purinergic receptor antagonist alone or in combination with a Stimulator of Interferon Genes (STING) antagonist.

  一方面，本发明提供了通过施用暴露于应激条件下的细胞产生的细胞后信号因子来提高免疫应答的方法。在一个方面，本发明提供了通过联合施用(a)干扰素基因刺激剂（STING）激动剂和(b)嘌呤能受体激动剂来增加免疫反应的方法。免疫反应的增强可用于治疗感染或癌症等。本发明还提供了筛选测定法，用于鉴定能诱导产生细胞后信号因子的化合物，这些细胞后信号因子也是免疫刺激剂。本发明进一步提供了鉴定具有免疫刺激活性的细胞后信号因子的方法。在另一方面，本发明提供了通过向细胞、组织或受试者单独施用嘌呤能受体拮抗剂或与干扰素基因刺激剂（STING）拮抗剂联合施用来降低免疫反应的方法。
• 4-BENZ0YL-1-SUBSTITUTED-PIPERAZIN-2-0NE DERIVATIVES AS P2X7 MODULATORS
  申请人：Glaxo Group Limited

  公开号：EP2212300A1

  公开（公告）日：2010-08-04
• METHODS OF MODULATING IMMUNE ACTIVITY
  申请人：Flagship Pioneering Innovations V, Inc.

  公开号：US20210299155A1

  公开（公告）日：2021-09-30

  In one aspect, the invention provides methods of increasing immune response by administering posteellular signaling factors produced by cells exposed to a stress condition. In one aspect, the invention provides methods of increasing immune response by administering in combination (a) a Stimulator of Interferon Genes (STING) agonist and (b) a purinergic receptor agonist. The increase in immune response may be used, for example, for treatment of infection or cancer. The invention also provides screening assays for identification of compounds that induce production of postcellular signaling factors which are also immunostimulatory agents. The invention further provides methods for identifying postcellular signaling factors with immunostimulatory activity. In another aspect, the invention provides methods of decreasing immune response by administering to a cell, tissue or subject a purinergic receptor antagonist alone or in combination with a Stimulator of Interferon Genes (STING) antagonist.
• [EN] 4-BENZ0YL-1-SUBSTITUTED-PIPERAZIN-2-0NE DERIVATIVES AS P2X7 MODULATORS<br/>[FR] DÉRIVÉS DE 4-BENZOYL-1-SUBSTITUÉ-PIPÉRAZIN-2-ONE COMME MODULATEURS DE P2X7
  申请人：GLAXO GROUP LTD

  公开号：WO2009053459A1

  公开（公告）日：2009-04-30

  The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein: A is C1-6alkyl, C3-6cycloalkyl, -CH2-R6, -CHMe-R7, -CMe2-R7, or optionally substituted aryl; wherein, when A is optionally substituted aryl, said aryl group is optionally substituted with 1 to 3 substituents, which may be the same or different, selected from the group consisting of halogen, C1-6alkyl, -CF3, C1-4alkoxy, C1fluoroalkoxy, cyano, NR8R9; and pyridyl wherein the pyridyl is optionally substituted by one methyl; R1 is chlorine, fluorine, -CF3, cyano or C1-6alkyl; R2, R3 and R5 independently are hydrogen, fluorine, chlorine, -CF3, cyano or C1-6alkyl, such that at least one of R2, R3 and R5 is other than hydrogen; R4 is hydrogen. These compounds and salts are thought to be P2X7 receptor antagonists. The invention also provides the use of the compound or salt for the manufacture of a medicament for the treatment of pain, inflammation, rheumatoid arthritis, osteoarthritis, or a neurodegenerative disease.

  该发明提供了一个具有以下式（I）的化合物或其药用盐，其中：A为C1-6烷基，C3-6环烷基，-CH2-R6，-CHMe-R7，-CMe2-R7或可选择地取代的芳基；其中，当A为可选择地取代的芳基时，所述芳基可选择地取代为1至3个取代基，这些取代基可以相同或不同，选自卤素，C1-6烷基，-CF3，C1-4烷氧基，C1氟烷氧基，氰基，NR8R9；和吡啶基，其中吡啶基可选择地被一个甲基取代；R1为氯，氟，-CF3，氰基或C1-6烷基；R2、R3和R5独立地为氢，氟，氯，-CF3，氰基或C1-6烷基，使得R2、R3和R5中至少有一个不是氢；R4为氢。这些化合物和盐被认为是P2X7受体拮抗剂。该发明还提供了该化合物或盐用于制备用于治疗疼痛、炎症、类风湿关节炎、骨关节炎或神经退行性疾病的药物的用途。