3-oxo-3-(4-(trifluoromethyl)phenyl)propyl (pyridin-3-ylmethyl)carbamodithioate

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-oxo-3-(4-(trifluoromethyl)phenyl)propyl (pyridin-3-ylmethyl)carbamodithioate
• 英文别名: 3-pyridinemethyldithiocarbamate-[2-(4-trifluoromethylbenzoyl)]ethyl ester；[3-oxo-3-[4-(trifluoromethyl)phenyl]propyl] N-(pyridin-3-ylmethyl)carbamodithioate
• 化学式: C₁₇H₁₅F₃N₂OS₂
• 分子量: 384.446
• InChiKey: QJBBVGUYWLKGGI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  99.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4'-三氟甲基苯乙酮 在 三乙胺 、 diisopropylammonium trifluoroacetate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 3-oxo-3-(4-(trifluoromethyl)phenyl)propyl (pyridin-3-ylmethyl)carbamodithioate
  参考文献：
  名称：

  New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds

  摘要：

  Pyruvate kinase M2 (PKM2) is a key protein responsible for cancer's Warburg effect. Activation of PKM2 may alter aberrant metabolism in cancer cells, which suggests PKM2 as a tumor selective therapeutic target. In this paper, the lead compound 8 was first discovered as a new kind of PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8 analogs were designed, synthesized and evaluated for their activation of PKM2 and anticancer activities. 7-Azaindole analog 32 was identified as the most potent PKM2 activator. Compounds with potent enzyme activity also exhibited selective anti-proliferation activity on cancer cell lines HCT116, Hela and H1299 compared with non-tumor cell line BEAS-2B. The structure-activity relationships of these compounds were supported by molecular docking results. Preliminary pharmacological studies also showed that compound 32 arrests the cell cycle at the G2/M phase in HCT116 cell line. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.05.041

文献信息

• PKM2 ACTIVATORS IN COMBINATION WITH REACTIVE OXYGEN SPECIES FOR TREATMENT OF CANCER
  申请人：TOLERO PHARMACEUTICALS, INC.

  公开号：US20200237766A1

  公开（公告）日：2020-07-30

  Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a PKM2 activator and an anti-cancer drug having a mechanism of action that increases production of reactive oxygen species in cancer cells to a patient in need thereof.
• [EN] PKM2 ACTIVATORS IN COMBINATION WITH REACTIVE OXYGEN SPECIES FOR TREATMENT OF CANCER<br/>[FR] ACTIVATEURS DE PKM2 EN COMBINAISON AVEC DES ESPÈCES RÉACTIVES DE L'OXYGÈNE POUR LE TRAITEMENT DU CANCER
  申请人：TOLERO PHARMACEUTICALS INC

  公开号：WO2019075367A1

  公开（公告）日：2019-04-18

  Combination therapies for treatment of cancer are provided. The disclosed methods comprise administration of a PKM2 activator and an anti-cancer drug having a mechanism of action that increases production of reactive oxygen species in cancer cells to a patient in need thereof.
• New pyridin-3-ylmethyl carbamodithioic esters activate pyruvate kinase M2 and potential anticancer lead compounds
  作者：Yu Zhang、Bin Liu、Xingyu Wu、Ridong Li、Xianling Ning、Yu Liu、Zhenming Liu、Zemei Ge、Runtao Li、Yuxin Yin

  DOI：10.1016/j.bmc.2015.05.041

  日期：2015.8

  Pyruvate kinase M2 (PKM2) is a key protein responsible for cancer's Warburg effect. Activation of PKM2 may alter aberrant metabolism in cancer cells, which suggests PKM2 as a tumor selective therapeutic target. In this paper, the lead compound 8 was first discovered as a new kind of PKM2 activator from a random screening of an in-house compound library. Then, a series of lead compound 8 analogs were designed, synthesized and evaluated for their activation of PKM2 and anticancer activities. 7-Azaindole analog 32 was identified as the most potent PKM2 activator. Compounds with potent enzyme activity also exhibited selective anti-proliferation activity on cancer cell lines HCT116, Hela and H1299 compared with non-tumor cell line BEAS-2B. The structure-activity relationships of these compounds were supported by molecular docking results. Preliminary pharmacological studies also showed that compound 32 arrests the cell cycle at the G2/M phase in HCT116 cell line. (C) 2015 Elsevier Ltd. All rights reserved.