(6R,10S)-11-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(5-fluoropyrimidin-2-yl)-5,6,7,8,9,10-hexahydro-6,10-epimino[1,2,4]triazolo[4,3-a]azocine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: (6R,10S)-11-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(5-fluoropyrimidin-2-yl)-5,6,7,8,9,10-hexahydro-6,10-epimino[1,2,4]triazolo[4,3-a]azocine
• 英文别名: [2-chloro-3-(trifluoromethyl)phenyl]-[(1S,8R)-5-(5-fluoropyrimidin-2-yl)-3,4,6,12-tetrazatricyclo[6.3.1.02,6]dodeca-2,4-dien-12-yl]methanone
• 化学式: C₂₀H₁₅ClF₄N₆O
• 分子量: 466.825
• InChiKey: OKEUHBTYCIUVSL-RISCZKNCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  32
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  76.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  11-{[2-chloro-3-(trifluoromethyl)phenyl]carbonyl}-3-(5-fluoropyrimidin-2-yl)-5,6,7,8,9,10-hexahydro-6,10-epimino[1,2,4]triazolo[4,3-a]azocine 在 CHIRALPAK AD-H (250×20 mm) column 作用下， 以 乙醇 、 二氧化碳 、 异丙醇 为溶剂， 以100%的产率得到
  参考文献：
  名称：

  US2014/275056

  摘要：

  公开号：

文献信息

• P2X7 MODULATORS
  申请人：JANSSEN PHARMACEUTICA NV

  公开号：US20160039836A1

  公开（公告）日：2016-02-11

  The present invention is directed to a compound of Formula (I): wherein: The present invention is directed to a compound of Formula (I): wherein: n is an integer from 0-1; X is CH2 when n is 0, or X is CH2 or oxygen when n is 1; R 1 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is optionally substituted with from 1 to 4 substituents independently selected from halogen and alkyl; and R 2 is S phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl, wherein the phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl is optionally substituted with from 1 to 2 substituents independently selected from the group consisting of halogen, alkyl, hydroxy and alkoxy. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). The compounds of formula (I) are useful as P2X7 modulators.

  本发明涉及一种式（I）的化合物：其中：n是0-1的整数；当n为0时，X是CH2，当n为1时，X是CH2或氧；R1是苯基或吡啶基，其中苯基或吡啶基可选地被1-4个取代基独立地选自卤素和烷基取代；R2是S苯基、吡啶基、吡嗪基、吡啶并嗪基、嘧啶基、吡咯基、吡唑基、噻唑基或噻吩基，其中苯基、吡啶基、吡嗪基、吡啶并嗪基、嘧啶基、吡咯基、吡唑基、噻唑基或噻吩基可选地被1-2个取代基独立地选自卤素、烷基、羟基和烷氧基。本发明还涉及包含式（I）化合物的药物组合物。式（I）化合物可用作P2X7调节剂。
• P2X7 modulators
  申请人：Jansssen Pharmaceutica NV

  公开号：US10053462B2

  公开（公告）日：2018-08-21

  The present invention is directed to a compound of Formula (I): wherein: n is an integer from 0-1; X is CH2 when n is 0, or X is CH2 or oxygen when n is 1; R1 is phenyl or pyridinyl, wherein the phenyl or pyridinyl is optionally substituted with from 1 to 4 substituents independently selected from halogen and alkyl; and R2 is phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl, wherein the phenyl, pyridinyl, pyrazinyl, pyradizinyl, pyrimidinyl, pyrrolyl, pyrazolyl, thiazolyl or thiophenyl is optionally substituted with from 1 to 2 substituents independently selected from the group consisting of halogen, alkyl, hydroxy and alkoxy. The invention also relates to pharmaceutical compositions comprising compounds of Formula (I). Methods of making and using the compounds of Formula (I) are also within the scope of the invention.

  本发明涉及一种式（I）化合物： 其中 n 是 0-1 之间的整数； 当 n 为 0 时，X 为 CH2，或当 n 为 1 时，X 为 CH2 或氧； R1 是苯基或吡啶基，其中苯基或吡啶基任选被 1 至 4 个独立选自卤素和烷基的取代基取代；以及 R2 是苯基、吡啶基、吡嗪基、嘧啶基、嘧啶基、吡咯基、吡唑基、噻唑基或噻吩基，其中苯基、吡啶基、吡嗪基、嘧啶基、吡咯基、吡唑基、噻唑基或噻吩基可任选被 1 至 2 个独立选自卤素、烷基、羟基和烷氧基的取代基取代。 本发明还涉及包含式（I）化合物的药物组合物。式（I）化合物的制造和使用方法也属于本发明的范围。
• 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。
• PHARMACEUTICAL COMPOSITION FOR ORAL ADMINISTRATION COMPRISING A P2X7 MODULATOR
  申请人：Janssen Pharmaceutica NV

  公开号：EP3309161B1

  公开（公告）日：2019-12-18
• US20140275056A1
  申请人：——

  公开号：US20140275056A1

  公开（公告）日：2014-09-18