2-[N-propargyl(4-chlorophenyl)aminomethyl]-3-phenyl-7-trifluoromethylquinoxaline | 958805-83-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 2-[N-propargyl(4-chlorophenyl)aminomethyl]-3-phenyl-7-trifluoromethylquinoxaline
• 英文别名: 4-chloro-N-[[3-phenyl-7-(trifluoromethyl)quinoxalin-2-yl]methyl]-N-prop-2-ynylaniline
• CAS: 958805-83-9
• 化学式: C₂₅H₁₇ClF₃N₃
• 分子量: 451.878
• InChiKey: QSOTZBYYNUJUCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  29
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  对氯苯胺 在 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基乙酰胺 、 甲苯 为溶剂， 反应 90.0h， 生成 2-[N-propargyl(4-chlorophenyl)aminomethyl]-3-phenyl-7-trifluoromethylquinoxaline
  参考文献：
  名称：

  2-[N-Alkyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines as anticancer agents inhibitors of folate enzymes

  摘要：

  Based on our previous results on the ascertained potent growth inhibition effect against a panel of 60 human tumors cell lines at National Cancer Institute of Bethesda (NCI), we have synthesized a novel series of thirty-one 2-[N-methyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines (1-31). The lead compound 1 was previously reported to be endowed with significant inhibition against hDHFR enzyme, with a Xi of 0.2 mu M. Docking studies were performed on compound 1 and here reported to predict its binding conformation to human dihydrofolate reductase (hDHFR). All compounds (1-31) were assayed versus hDHFR and human thymidylate synthase (hTS). From the screening emerged that all compounds inhibited hDHFR with Xi values included between 0.2 and 11 mu M, while only a few (6, 21, 24, 27, 29) showed great activity and selectivity towards hTS. Evaluation of the anticancer activity was performed by NCI, first against the three cell line panel, and only the most active compounds (17, 21, 24, 26, 27) were evaluated on a panel of 60 human tumor cell lines. Compound 21 was the most active against all cell lines with log GI50 equal to -5.49 and log LC50 equal to -4.19 and maintained significant percent of growth inhibition on seven cancer cell lines at the concentration of 1 mu M. Compound 17 was the second most active and moreover showed interesting selectivity against some cell lines (Lung cancer: A549/ATCC, Melanoma: UACC-257, Ovarian Cancer: ovcar-8 and Renal cancer: RXF 393) at all concentration examined (100-0.01 mu M). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.01.048

文献信息

• 2-[N-Alkyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines as anticancer agents inhibitors of folate enzymes
  作者：Sandra Piras、Antonio Carta、Irene Briguglio、Paola Corona、Giuseppe Paglietti、Rosaria Luciani、Maria Paola Costi、Stefania Ferrari

  DOI：10.1016/j.ejmech.2014.01.048

  日期：2014.3

  Based on our previous results on the ascertained potent growth inhibition effect against a panel of 60 human tumors cell lines at National Cancer Institute of Bethesda (NCI), we have synthesized a novel series of thirty-one 2-[N-methyl(R-phenyl)-aminomethyl]-3-phenyl-7-trifluoromethylquinoxalines (1-31). The lead compound 1 was previously reported to be endowed with significant inhibition against hDHFR enzyme, with a Xi of 0.2 mu M. Docking studies were performed on compound 1 and here reported to predict its binding conformation to human dihydrofolate reductase (hDHFR). All compounds (1-31) were assayed versus hDHFR and human thymidylate synthase (hTS). From the screening emerged that all compounds inhibited hDHFR with Xi values included between 0.2 and 11 mu M, while only a few (6, 21, 24, 27, 29) showed great activity and selectivity towards hTS. Evaluation of the anticancer activity was performed by NCI, first against the three cell line panel, and only the most active compounds (17, 21, 24, 26, 27) were evaluated on a panel of 60 human tumor cell lines. Compound 21 was the most active against all cell lines with log GI50 equal to -5.49 and log LC50 equal to -4.19 and maintained significant percent of growth inhibition on seven cancer cell lines at the concentration of 1 mu M. Compound 17 was the second most active and moreover showed interesting selectivity against some cell lines (Lung cancer: A549/ATCC, Melanoma: UACC-257, Ovarian Cancer: ovcar-8 and Renal cancer: RXF 393) at all concentration examined (100-0.01 mu M). (C) 2014 Elsevier Masson SAS. All rights reserved.