N-(4-乙基苯基)-N'-1H-吲哚-3-基脲 | 941987-60-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: N-(4-乙基苯基)-N'-1H-吲哚-3-基脲
• 英文名称: H-151
• 英文别名: 1-(4-ethylphenyl)-3-(1H-indol-3-yl)urea
• CAS: 941987-60-6
• 化学式: C₁₇H₁₇N₃O
• 分子量: 279.341
• InChiKey: UJZDIKVQFMCLBE-UHFFFAOYSA-N

物化性质

• 沸点：
  399.9±25.0 °C(Predicted)
• 密度：
  1.298±0.06 g/cm3(Predicted)
• 溶解度：
  溶于 DMSO (25 mg/ml)

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  56.9
• 氢给体数：
  3
• 氢受体数：
  1

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

制备方法与用途

生物活性

H-151是STING的共价拮抗剂，在人细胞和体内均具有显著的抑制活性。

靶点

Target	Value
STING ()

体外研究

H-151 (0.02-2 μM) reduces IFNβ luciferase reporter measurements of HEK293T cells.
H-151 (0.5 μM; 2 h) inhibits the phosphorylation of TBK1 in THP-1 cells.
H-151 (1 μM; 3 h) suppresses hsSTING palmitoylation.

体内研究

H-151 (750 nmol per mouse; a single i.p.) markedly reduces systemic cytokine responses in CMA-treated mice.
H-151 (750 nmol per mouse; i.p. daily for 7 d) exhibits notable efficacy in Trex1 ^−/− mice that expressed a bioluminescent IFNβ reporter.
H-151 (750 nmol per mouse; i.p.) reaches effective systemic levels, displays a short half-life in the serum and forms an adduct to mmSTING in wild-type mice.

反应信息

• 作为产物：
  描述：

  3-异氰酰基-1H-吲哚 、 4-乙基苯胺 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以79%的产率得到N-(4-乙基苯基)-N'-1H-吲哚-3-基脲
  参考文献：
  名称：

  [EN] STING INHIBITORS
  [FR] INHIBITEURS DE STING

  摘要：

  本发明涉及化合物、用于治疗STING相关疾病、病况或障碍的组合物和方法。

  公开号：

  WO2019201939A1

文献信息

• STING INHIBITORS
  申请人：ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE (EPFL)

  公开号：EP3556362A1

  公开（公告）日：2019-10-23

  The present invention relates to compounds, compositions for use and methods for the treatment of a STING associated disease, condition, or disorder.

  本发明涉及治疗 STING 相关疾病、病症或紊乱的化合物、用途组合物和方法。
• 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。
• DENDRIMER COMPOSITIONS AND METHODS FOR DRUG DELIVERY
  申请人：Ashvattha Therapeutics, Inc.

  公开号：US20210170040A1

  公开（公告）日：2021-06-10

  Dendrimer compositions and methods for the treatment of cancer or autoimmune diseases are described. The compositions include dendrimers complexed or conjugated with one or more active agents for the treatment or alleviation of one or more symptoms of cancer or autoimmune diseases. The dendrimers may include one or more ethylene diamine-core poly(amidoamine) (PAMAM) hydroxyl-terminated generation-4, 5, 6, 7, 8, 9, or 10 dendrimers. The active agents may be immunomodulatory agents such as STING agonists, CSF1R inhibitors, PARP inhibitors, VEGFR tyrosine kinase inhibitors, MEK inhibitors, glutaminase inhibitors, TIE II antagonists, and CXCR2 inhibitors, and STING antagonists. Methods of using the dendrimer compositions to treat cancer, bone disease or inflammatory diseases are also provided.
• 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.
• METHODS FOR TREATING AUTOIMMUNE OR AUTOINFLAMMATORY DISEASE
  申请人：UNIVERSITY OF WASHINGTON

  公开号：US20220143035A1

  公开（公告）日：2022-05-12

  The disclosure provides method and compositions for treating of an autoimmune disease or an autoinflammatory disease, including administering to a subject in need thereof an amount effective of a DNA-dependent protein kinase (DNA-PK) inhibitor and/or an inhibitor of HSPA8/HSC70.