6-chloro-2-(trifluoromethyl)-N-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-chloro-2-(trifluoromethyl)-N-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamide
• 英文别名: 6-chloro-2-(trifluoromethyl)-N-[4-(trifluoromethyl)phenyl]-1H-benzimidazole-4-carboxamide
• 化学式: C₁₆H₈ClF₆N₃O
• 分子量: 407.702
• InChiKey: MWNNIGRGNSXNEA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  27
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  57.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-氯-2-甲基-6-硝基苯胺 在 potassium permanganate 、 氢气 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 、 sodium hydroxide 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.17h， 生成 6-chloro-2-(trifluoromethyl)-N-(4-(trifluoromethyl)phenyl)-1H-benzo[d]imidazole-4-carboxamide
  参考文献：
  名称：

  鉴定 DK419，一种 Wnt/β-连环蛋白信号传导和结直肠癌生长的有效抑制剂

  摘要：

  Wnt 信号通路对于正常组织发育至关重要，并且在失调时是疾病的潜在机制。此前，我们报道了药物氯硝柳胺通过降低胞浆中Disheveled和β-catenin的水平来抑制Wnt/β-catenin信号传导，并在体外和体内抑制结肠癌的生长。自从发现氯硝柳胺的驱虫活性以来，越来越多的文献表明氯硝柳胺是一种多功能药物。为了鉴定具有改进的药代动力学特性的氯硝柳胺衍生物，以维持氯硝柳胺的多功能药物活性以进行临床评估，我们设计了 DK419，一种含有 1H-苯并[ d ]咪唑-4-甲酰胺亚结构的衍生物，利用结构-活性氯硝柳胺水杨酰苯胺化学型的关系（SAR）。与氯硝柳胺类似，我们发现 DK419 抑制 Wnt/β-连环蛋白信号传导，改变细胞耗氧率并诱导 pAMPK 的产生。此外，我们发现DK419在体外抑制CRC肿瘤细胞的生长，口服给药时具有良好的血浆暴露，并且在口服给药的小鼠中抑制患者来源的CRC240肿瘤外植体的生长。

  DOI：

  10.1016/j.bmc.2018.09.016

文献信息

• CHEMICAL MODULATORS OF IMMUNE CHECKPOINTS AND THERAPEUTIC USE
  申请人：Duke University

  公开号：US20170190675A1

  公开（公告）日：2017-07-06

  Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

  提供了下调免疫检查点如PD-1、PD-L1和CTLA-4的化合物和药物组合物。还提供了通过下调免疫检查点如PD-1、PD-L1和CTLA-4来治疗疾病的方法。这些方法对于治疗受试者的癌症和病毒感染是有用的。
• [EN] NICLOSAMIDE ANALOGUES AND THERAPEUTIC USE THEREOF<br/>[FR] ANALOGUES DE NICLOSAMIDE ET LEUR UTILISATION THÉRAPEUTIQUE
  申请人：UNIV DUKE

  公开号：WO2020028392A1

  公开（公告）日：2020-02-06

  Described are niclosamide analogue compounds, pharmaceutical compositions thereof, and method of using the compounds and compositions for treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway, such as cancer, fatty liver, antibiotic resistance, and viral infection. The disclosed compounds and compositions may also he used for modulating mitochondrial function and for treating certain non-cancer diseases and/or diorders, such as diabetes, fibrotic disease, primary sclerosing cholangitis.

  本文描述了尼氯酰胺类似物化合物，其制药组合物以及使用这些化合物和组合物治疗与Wnt/Frizzled信号通路失调相关的疾病的方法，例如癌症、脂肪肝、抗生素耐药和病毒感染。所披露的化合物和组合物也可用于调节线粒体功能和治疗某些非癌症疾病和/或障碍，例如糖尿病、纤维化疾病和原发性硬化性胆管炎。
• Chemical modulators of immune checkpoints and therapeutic use
  申请人：Duke University

  公开号：US10189797B2

  公开（公告）日：2019-01-29

  Compounds and pharmaceutical compositions that down-regulate immune checkpoints such as PD-1, PD-L1 and CTLA-4 are provided. Also provided are methods of treating a disease by down-regulating immune checkpoints such as PD-1, PD-L1 and CTLA-4. The methods are useful for treating cancer and viral infection in a subject.

  提供了下调免疫检查点如 PD-1、PD-L1 和 CTLA-4 的化合物和药物组合物。还提供了通过下调免疫检查点如 PD-1、PD-L1 和 CTLA-4 来治疗疾病的方法。这些方法可用于治疗受试者的癌症和病毒感染。
• NICLOSAMIDE ANALOGUES AND THERAPEUTIC USE THEREOF
  申请人：Duke University

  公开号：US20210179615A1

  公开（公告）日：2021-06-17

  Described are niclosamide analogue compounds, pharmaceutical compositions thereof, and method of using the corner pounds and compositions for treating a disease associated with dysregulation of the Wnt/Frizzled signaling pathway, such as cancer, fatty liver, antibiotic resistance, and viral infection. The disclosed compounds and compositions may also be used for modulating mitochondrial function and for treating certain non-cancer diseases and/or diorders, such as diabetes, fibrotic disease, primary sclerosing cholangitis.
• PHARMACEUTICAL COMBINATION OF WNT SIGNALING AND MACC1 INHIBITORS
  申请人：Max-Delbrück-Centrum für Molekulare Medizin in der Holmholtz-Gemeinschafft

  公开号：US20220125807A1

  公开（公告）日：2022-04-28

  A pharmaceutical combination, includes an inhibitor of the Wnt/β-catenin signaling pathway and an inhibitor of MACC1. One combination includes an inhibitor of S100A4 as a Wnt-signaling inhibitor, preferably niclosamide, and a statin or MEK1 inhibitor as an inhibitor of MACC1. A pharmaceutical composition can include the combination. The combination or composition can be used in the treatment of a tumor disease, such as a solid tumor, and/or for the treatment and/or prophylaxis of tumor metastasis.