5-(4-Fluorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazole-2-carbothioamide | 1424400-79-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 5-(4-Fluorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazole-2-carbothioamide
• 英文别名: 5-(4-fluorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazole-2-carbothioamide
• CAS: 1424400-79-2
• 化学式: C₂₀H₁₆FN₃S
• 分子量: 349.432
• InChiKey: XFEHHJQRPUGUMO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  73.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-(4-Fluorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazole-2-carbothioamide 、 溴乙酸 在 sodium acetate 、 乙酸酐 作用下， 以 溶剂黄146 为溶剂， 以66%的产率得到2-(3-(4-fluorophenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one
  参考文献：
  名称：

  Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents

  摘要：

  A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a-7a, 1b-7b, 1c-7c, 1d-7d) were firstly synthesized and their anti-proliferative activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl) thiazol-4(5H)-one (7d) displayed the most potent inhibitory activity (IC50 = 0.86 mu M for Hela and IC50 = 0.12 mu M for EGFR). Structure-activity relationship (SAR) analysis showed that the anti-proliferative activity was affected by A-ring-substituent (-OCH3 > -CH3 > -H > -Br > -Cl > -F). Docking simulation of compound 7d into EGFR active site showed that naphthalene ring of 7d with LYS721 formed two p-pi bonds, which enhanced antitumor activity. Therefore, compound 7d may be developed as a potential antitumor agent. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.03.072
• 作为产物：
  描述：

  4-氟苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 反应 5.0h， 生成 5-(4-Fluorophenyl)-3-naphthalen-2-yl-3,4-dihydropyrazole-2-carbothioamide
  参考文献：
  名称：

  Design, modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thiourea skeleton as anticancer agents

  摘要：

  Two series of novel naphthalin-containing pyrazoline derivatives C1-C14 and D1-D14 have been synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. Compound D14 displayed the most potent activity against EGFR and A549 cell line (IC50 = 0.05 mu M and GI(50) = 0.11 mu M), being comparable with the positive control Erlotinib (IC50 = 0.03 mu M and GI(50) = 0.03 mu M) and more potent than our previous compounds C0-A (IC50 = 5.31 mu M and GI(50) = 33.47 mu M) and C0-B (IC50 = 0.09 mu M and GI(50) = 0.34 mu M). Meanwhile, compound C14 displayed the most potent activity against HER-2 and MCF-7 cell line (IC50 = 0.88 mu M and GI(50) = 0.35 mu M), being a little less potent than Erlotinib (IC50 = 0.16 mu M and GI(50) = 0.08 mu M) but far more potent than C0-A (IC50 = 6.58 mu M and GI(50) = 27.62 mu M) and C0-B (IC50 = 2.77 mu M and GI(50) = 3.79 mu M). The docking simulation was performed to analyze the probable binding models and the QSAR models were built for reasonable design of EGFR/HER-2 inhibitors at present and in future. The structural modification of introducing naphthalin moiety reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity. Moreover, the replacement of thiourea skeleton by using benzene ring resulted in the slight diversity of the two series towards specific targets. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.01.013

文献信息

• Design, modification and 3D QSAR studies of novel naphthalin-containing pyrazoline derivatives with/without thiourea skeleton as anticancer agents
  作者：Wen Yang、Yang Hu、Yu-Shun Yang、Fei Zhang、Yan-Bin Zhang、Xiao-Liang Wang、Jian-Feng Tang、Wei-Qing Zhong、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2013.01.013

  日期：2013.3

  Two series of novel naphthalin-containing pyrazoline derivatives C1-C14 and D1-D14 have been synthesized and evaluated for their EGFR/HER-2 inhibitory and anti-proliferation activities. Compound D14 displayed the most potent activity against EGFR and A549 cell line (IC50 = 0.05 mu M and GI(50) = 0.11 mu M), being comparable with the positive control Erlotinib (IC50 = 0.03 mu M and GI(50) = 0.03 mu M) and more potent than our previous compounds C0-A (IC50 = 5.31 mu M and GI(50) = 33.47 mu M) and C0-B (IC50 = 0.09 mu M and GI(50) = 0.34 mu M). Meanwhile, compound C14 displayed the most potent activity against HER-2 and MCF-7 cell line (IC50 = 0.88 mu M and GI(50) = 0.35 mu M), being a little less potent than Erlotinib (IC50 = 0.16 mu M and GI(50) = 0.08 mu M) but far more potent than C0-A (IC50 = 6.58 mu M and GI(50) = 27.62 mu M) and C0-B (IC50 = 2.77 mu M and GI(50) = 3.79 mu M). The docking simulation was performed to analyze the probable binding models and the QSAR models were built for reasonable design of EGFR/HER-2 inhibitors at present and in future. The structural modification of introducing naphthalin moiety reinforced the combination of our compounds and the receptor, resulting in progress of bioactivity. Moreover, the replacement of thiourea skeleton by using benzene ring resulted in the slight diversity of the two series towards specific targets. (C) 2013 Elsevier Ltd. All rights reserved.
• Synthesis and biological evaluation of compounds which contain pyrazole, thiazole and naphthalene ring as antitumor agents
  作者：Ji-Wen Yuan、She-Feng Wang、Zhong-Liang Luo、Han-Yue Qiu、Peng-Fei Wang、Xin Zhang、Yong-An Yang、Yong Yin、Fei Zhang、Hai-Liang Zhu

  DOI：10.1016/j.bmcl.2014.03.072

  日期：2014.5

  A series of compounds which contain pyrazole, thiazole and naphthalene ring (1a-7a, 1b-7b, 1c-7c, 1d-7d) were firstly synthesized and their anti-proliferative activity, EGFR inhibitory activity, cytotoxicity and inhibition to Hela cell migration were evaluated. Compound 2-(3-(3,4-dimethylphenyl)-5-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl) thiazol-4(5H)-one (7d) displayed the most potent inhibitory activity (IC50 = 0.86 mu M for Hela and IC50 = 0.12 mu M for EGFR). Structure-activity relationship (SAR) analysis showed that the anti-proliferative activity was affected by A-ring-substituent (-OCH3 > -CH3 > -H > -Br > -Cl > -F). Docking simulation of compound 7d into EGFR active site showed that naphthalene ring of 7d with LYS721 formed two p-pi bonds, which enhanced antitumor activity. Therefore, compound 7d may be developed as a potential antitumor agent. (C) 2014 Elsevier Ltd. All rights reserved.