N-{[2-氯-3-(三氟甲基)苯基]甲基}-1-甲基-5-氧代-L-脯氨酰胺 | 1001389-72-5

• 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
• 中文名称: N-{[2-氯-3-(三氟甲基)苯基]甲基}-1-甲基-5-氧代-L-脯氨酰胺
• 英文名称: GSK1482160
• 英文别名: 2-Pyrrolidinecarboxamide, N-((2-chloro-3-(trifluoromethyl)phenyl)methyl)-1-methyl-5-oxo-, (2S)-；(2S)-N-[[2-chloro-3-(trifluoromethyl)phenyl]methyl]-1-methyl-5-oxopyrrolidine-2-carboxamide
• CAS: 1001389-72-5
• 化学式: C₁₄H₁₄ClF₃N₂O₂
• 分子量: 334.726
• InChiKey: BJEMSIVBBUBXMZ-JTQLQIEISA-N

物化性质

• 沸点：
  517.6±50.0 °C(Predicted)
• 密度：
  1.380±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

GSK-1482160是一种口服的P2X7受体负性变构调节剂，能够参与调控中枢和外周免疫细胞产生促炎症细胞因子，如IL-1β。因此，GSK-1482160具有研究炎症疾病的潜力。

反应信息

• 作为产物：
  描述：

  2-氯-3-(三氟甲基)苄胺 在 2-乙氧基-1-乙氧碳酰基-1,2-二氢喹啉 作用下， 以 DCM 、 二氯甲烷 为溶剂， 反应 0.58h， 以99.1%的产率得到
  参考文献：
  名称：

  Novel Receptor Antagonists and Their Methods of Use

  摘要：

  本发明涉及一种新型的氧代脯氨酰胺衍生物，其化学式为（I），可以调节P2X7受体功能，并能够拮抗P2X7受体上ATP的作用，以及利用这些化合物或其药物组合物治疗由P2X7受体介导的疾病，例如疼痛、炎症和神经退行性疾病。

  公开号：

  US20080009541A1

文献信息

• Hetero-aryl bromide precursor fluorine-18 radiosynthesis and preclinical evaluation of a novel positron emission tomography (PET) tracer [18F]GSK1482160
  作者：Guolong Huang、Xiaolei Lu、Yifan Qiu、Lei Bi、Peizhen Ye、Min Yang、Yanfang Shen、Hongjun Jin、Junbin Han

  DOI：10.1016/j.bmc.2022.116996

  日期：2022.11

  radiosynthesized by hetero-aryl bromides precursor 10 with [18F]Et4NF, 20–30 % radiochemical yield, > 68 GBq/μmol specific activity, >98 % radiochemical purity. Evaluation in healthy male Sprague-Dawley rats revealed that [18F]GSK1482160 ([18F]11) was stably retained 87.81 %, 72.45 %, and 56.32 % in brain, blood and liver respectively 60-min post-injection. Ex-vivo biodistribution of [18F]11 proved that it was able

  嘌呤能 P2X7 受体 (P2X7R) 是一种 ATP 门控离子通道，是各种炎症性免疫和神经退行性疾病的重要治疗靶点。一种新型 P2X7R 靶向放射性示踪剂 GSK1482160 由具有 [ 18 F]Et 4 NF 的杂芳基溴前体10放射合成，放射化学产率为 20-30%，比活度 > 68 GBq/μmol，放射化学纯度 >98%。对健康雄性 Sprague-Dawley 大鼠的评估显示，注射后 60 分钟，[ 18 F]GSK1482160 ([ 18 F]11)在脑、血液和肝脏中分别稳定保留 87.81%、72.45% 和 56.32%。[ 18 F]11的离体生物分布证明它能够在体内靶向P2X7R，并且在主要器官中没有脱氟。PET/MRI 成像和放射自显影显示[ 18 F]11能够穿透血脑屏障 (BBB)，是一种有前途的用于临床转化的 P2X7R PET 放射性配体。
• 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。
• SUBSTITUTED N-PHENYLMETHYL -5-OXO-PROLINE-2-AMIDES AS P2X7-RECEPTOR ANTAGONISTS AND THEIR METHODS OF USE
  申请人：Glaxo Group Limited

  公开号：EP2049478B1

  公开（公告）日：2012-05-30
• 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.
• US7718693B2
  申请人：——

  公开号：US7718693B2

  公开（公告）日：2010-05-18