3,4-difluorophenylpropargylamine | 1225892-02-3

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 3,4-difluorophenylpropargylamine
• 英文别名: 3,4-difluoro-N-prop-2-ynylaniline
• CAS: 1225892-02-3
• 化学式: C₉H₇F₂N
• 分子量: 167.158
• InChiKey: NHVIGCNUCAGQEH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  12
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3,4-difluorophenylpropargylamine 、 2-bromomethyl-3-phenyl-7-trifluoromethylquinoxaline 以 N,N-二甲基乙酰胺 为溶剂， 反应 72.0h， 以19%的产率得到2-[N-propargyl(3,4-difluorophenyl)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
• 作为产物：
  描述：

  3-溴丙炔 、 3,4-二氟苯胺 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 3,4-difluorophenylpropargylamine
  参考文献：
  名称：

  发现具有抗肺纤维化活性的一系列新的hDHODH抑制剂。

  摘要：

  人二氢乳清酸酯脱氢酶（hDHODH）是从头进行嘧啶从头生物合成必不可少的黄素依赖性酶，它是治疗自身免疫性疾病的有吸引力的治疗靶标。基于通过药物化学探索获得的铅，开发了一系列新的hDHODH抑制剂。大多数化合物显示出对hDHODH的中度至显着效力，化合物5d，5e和6a有效抑制hDHODH的活性，IC50值为0.9至2.8μM。进一步的研究表明，化合物5e还可以有效抑制活化的PBMC的增殖（IC50 = 20.35μM）。令人惊讶地，化合物5e还显示出与吡非尼酮体外测定相似的抗肺纤维化活性。所以，

  DOI：

  10.1016/j.bioorg.2019.01.011

文献信息

• Design, synthesis and biological evaluation of novel aryl-acrylic derivatives as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors
  作者：Hao Hu、Ming Li、Di Wu、Zhiwei Li、Ruifeng Miao、Yajing Liu、Ping Gong

  DOI：10.1016/j.bmc.2019.05.048

  日期：2019.7

  Two series of novel aryl-acrylic derivatives were designed, synthesized, and screened in enzymatic and cellular inhibitory activities. All compounds showed moderate to significant potency. The SAR analyses indicated that the semicarbazone linker is better than the 1,2,3-triazole linker. Among semicarbazone compounds that R1 bearing di-chain amino groups exhibited superior activities to those with morpholino

  设计，合成和筛选了两个系列的新型芳基-丙烯酸衍生物的酶和细胞抑制活性。所有化合物均显示中等至显着的效力。SAR分析表明，半碳环接头比1,2,3-三唑接头更好。在带有R1的双链氨基的半脲化合物中，具有比吗啉代基团更高的活性。此外，在末端苯环的2-位或4-位具有吸电子基团的化合物更具活性。在这些化合物中，化合物7g，7i，7m和7n在低微摩尔范围内显示出抑制能力，并且对正常HeLa细胞的细胞毒性水平可忽略不计。此外，研究表明，芳基丙烯酸是抑制IDO1的有趣新型支架，可进一步开发。
• 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.
• Discovery of a novel series of hDHODH inhibitors with anti-pulmonary fibrotic activities
  作者：Kuan Lu、Yanfang Zhao、Guodong Wu、Hao Hu、Mingzhong Wang、Guowei Gong、Yuyang Jiang

  DOI：10.1016/j.bioorg.2019.01.011

  日期：2019.5

  Human dihydroorotate dehydrogenase (hDHODH) is a flavin-dependent enzyme essential to pyrimidine de novo biosynthesis, which serves as an attractive therapeutic target for the treatment of autoimmune disorders. A novel series of hDHODH inhibitors was developed based on a lead which was obtained by a medicinal chemistry exploration. Most compounds showed moderate to significant potency against hDHODH

  人二氢乳清酸酯脱氢酶（hDHODH）是从头进行嘧啶从头生物合成必不可少的黄素依赖性酶，它是治疗自身免疫性疾病的有吸引力的治疗靶标。基于通过药物化学探索获得的铅，开发了一系列新的hDHODH抑制剂。大多数化合物显示出对hDHODH的中度至显着效力，化合物5d，5e和6a有效抑制hDHODH的活性，IC50值为0.9至2.8μM。进一步的研究表明，化合物5e还可以有效抑制活化的PBMC的增殖（IC50 = 20.35μM）。令人惊讶地，化合物5e还显示出与吡非尼酮体外测定相似的抗肺纤维化活性。所以，