[2-Methoxy-5-(2,4,5-trifluoro-3-methoxybenzoyl)phenyl] 2-chloroacetate | 1434871-02-9

• 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: [2-Methoxy-5-(2,4,5-trifluoro-3-methoxybenzoyl)phenyl] 2-chloroacetate
• 英文别名: [2-methoxy-5-(2,4,5-trifluoro-3-methoxybenzoyl)phenyl] 2-chloroacetate
• CAS: 1434871-02-9
• 化学式: C₁₇H₁₂ClF₃O₅
• 分子量: 388.727
• InChiKey: BPETZROOEUQPAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [2-Methoxy-5-(2,4,5-trifluoro-3-methoxybenzoyl)phenyl] 2-chloroacetate 在 potassium tert-butylate 、 sodium acetate 、 甲基三苯基溴化膦 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 26.0h， 生成 2-Methoxy-5-[1-(2,4,5-trifluoro-3-methoxyphenyl)ethenyl]phenol
  参考文献：
  名称：

  抗有丝分裂苯达他汀的氟类似物的合成及生物学评价

  摘要：

  为了研究氟的影响，尤其是对A环的影响，合成了一系列新的非他汀（3）的氟类似物（7a – l），并测试了其与微管蛋白聚合反应的相互作用，并评估了其对NCI的细胞毒性。 -60人癌细胞系面板。我们已经表明，用2,4,5-三氟-3-甲氧基苯基单元代替苯达他汀的3,4,5-三甲氧基苯基A-环，导致了抗微管蛋白和细胞毒性作用的保守。氟异康他汀7k是本研究中最有效的抗癌药，对白血病细胞SR（GI 50  = 15 nM）和HL-60（TB）（GI）具有最高的抗增殖潜力50  = 23 nM）和黑色素瘤细胞系MDA-MB-435（GI 50  = 19 nM）。

  DOI：

  10.1016/j.bmc.2013.03.064
• 作为产物：
  描述：

  (2-甲氧基苯基)2-氯乙酸酯 、 3-甲氧基-2,4,5-三氟苯甲酸 在 甲烷磺酸 、 四磷十氧化物 作用下， 反应 14.0h， 以90%的产率得到[2-Methoxy-5-(2,4,5-trifluoro-3-methoxybenzoyl)phenyl] 2-chloroacetate
  参考文献：
  名称：

  抗有丝分裂苯达他汀的氟类似物的合成及生物学评价

  摘要：

  为了研究氟的影响，尤其是对A环的影响，合成了一系列新的非他汀（3）的氟类似物（7a – l），并测试了其与微管蛋白聚合反应的相互作用，并评估了其对NCI的细胞毒性。 -60人癌细胞系面板。我们已经表明，用2,4,5-三氟-3-甲氧基苯基单元代替苯达他汀的3,4,5-三甲氧基苯基A-环，导致了抗微管蛋白和细胞毒性作用的保守。氟异康他汀7k是本研究中最有效的抗癌药，对白血病细胞SR（GI 50  = 15 nM）和HL-60（TB）（GI）具有最高的抗增殖潜力50  = 23 nM）和黑色素瘤细胞系MDA-MB-435（GI 50  = 19 nM）。

  DOI：

  10.1016/j.bmc.2013.03.064

文献信息

• Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands
  作者：Alina Ghinet、Xavier Thuru、Emilie Floquet、Joëlle Dubois、Amaury Farce、Benoît Rigo

  DOI：10.1016/j.bioorg.2020.103643

  日期：2020.3

  The majority of cancers detected every year are treated with anti-cancer compounds. Unfortunately, many tumors become resistant to antineoplastic drugs. One option is to use cocktails of compounds acting on different targets to try to overcome the resistant cells. This type of approach can produce good results, but is often accompanied by a sharp increase of associated side effects.The strategy presented herein focuses on the use of a single compound acting on two different biological targets enhancing potency and lowering the toxicity of the chemotherapy. In this light, the approach presented in the current study involves the dual inhibition of human pyruvate dehydrogenase kinase-1 (PDHK1) and tubulin polymerization using mono-, di- and tri-chloroacetate-loaded benzophenones and benzothiophenones.Synthesized molecules were evaluated in vitro on tubulin polymerization and on pyruvate dehydrogenase kinase 1. The cell cycle distribution after treatment of DA1-3b leukemic cells with active compounds was tested.Twenty-two benzo(thio)phenones have been selected by the National Cancer Institute (USA) for evaluation of their anti-proliferative potential against NCI-60 cancer cell lines including multidrug-resistant tumor cell lines. Seventeen molecules proved to be very effective in combating the growth of tumor cells exhibiting inhibitory activities up to nanomolar range.The molecular docking of best antitumor molecules in the study was realized with GOLD in the tubulin and PDHK1 binding sites, and allowed to understand the positioning of active molecules.Chloroacetate-loaded benzo(thio)phenones are dual targeted tubulin- and pyruvate dehydrogenase kinase 1 (PDHK1)-binding antitumor agents and exhibited superior antitumor activity compared to non-chlorinated congeners particularly on leukemia, colon, melanoma and breast cancer cell lines.