3-(4-fluorophenyl)-4,5-dihydro-5-(4-methoxyphenyl)pyrazole-1-carbothioamide

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 3-(4-fluorophenyl)-4,5-dihydro-5-(4-methoxyphenyl)pyrazole-1-carbothioamide
• 英文别名: 5-(4-Fluorophenyl)-3-(4-methoxyphenyl)-3,4-dihydropyrazole-2-carbothioamide
• 化学式: C₁₇H₁₆FN₃OS
• 分子量: 329.398
• InChiKey: HORYFSIAXZQJKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-fluorophenyl)-4,5-dihydro-5-(4-methoxyphenyl)pyrazole-1-carbothioamide 、 溴乙酸 在 sodium acetate 、 乙酸酐 、 溶剂黄146 作用下， 以85%的产率得到2-(3-(4-fluorophenyl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors

  摘要：

  A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC50 = 0.24 mu M for EGFR and IC50 = 1.07 mu M for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC50 value of 0.30, 0.54, and 0.70 mu M, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.051
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 3-(4-fluorophenyl)-4,5-dihydro-5-(4-methoxyphenyl)pyrazole-1-carbothioamide
  参考文献：
  名称：

  查耳酮类吡唑啉衍生物互变异构体的合成，光谱和计算表征

  摘要：

  在本研究中，已合成了一系列新型吡唑啉衍生物，并根据FT-Raman，1 H和13确定了它们的结构C NMR光谱数据和DFT计算值。联合计算研究使用B3LYP / 6-311G（2d，2p）密度泛函理论和FT-Raman研究3-（4-取代-苯基）-4,5-二氢-5-（4-取代-提出了苯基）吡唑-1-碳硫酰胺和3-（4-取代-苯基）-4,5-二氢-5-（4-取代-苯基）吡唑-1-羧酰胺。使用DFT将结构表征为势能表面中的最小值。计算得出的拉曼光谱和NMR光谱与实验结果非常吻合，因此已详细讨论了互变异构形式之间的平衡。我们的研究表明存在互变异构体，羧酰胺/碳硫酰胺基团可能以固态或溶液形式互变异构。计算得出的热力学数据表明，R（CS）NH2和R（C O）NH 2物种比R（C NH）SH和R（C NH）OH物种更稳定。此外，发现1 H NMR位移的结果指出存在哪种结构。

  DOI：

  10.1016/j.saa.2015.07.041

文献信息

• Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors
  作者：Ke-Ming Qiu、Hai-Hong Wang、Li-Ming Wang、Yin Luo、Xian-Hui Yang、Xiao-Ming Wang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.01.051

  日期：2012.3

  A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC50 = 0.24 mu M for EGFR and IC50 = 1.07 mu M for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC50 value of 0.30, 0.54, and 0.70 mu M, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent. (C) 2012 Elsevier Ltd. All rights reserved.
• Synthesis, spectroscopic and computational characterization of the tautomerism of pyrazoline derivatives from chalcones
  作者：Fábio Balbino Miguel、Juliana Arantes Dantas、Stefany Amorim、Gustavo F.S. Andrade、Luiz Antônio Sodré Costa、Mara Rubia Costa Couri

  DOI：10.1016/j.saa.2015.07.041

  日期：2016.1

  Raman and NMR spectra were of such remarkable agreement to the experimental results that the equilibrium between tautomeric forms has been discussed in detail. Our study suggests the existence of tautomers, the carboxamide/carbothioamide group may tautomerize, in the solid state or in solution. Thermodynamic data calculated suggests that the R(CS)NH2 and R(CO)NH2 species are more stable than the R(CNH)SH

  在本研究中，已合成了一系列新型吡唑啉衍生物，并根据FT-Raman，1 H和13确定了它们的结构C NMR光谱数据和DFT计算值。联合计算研究使用B3LYP / 6-311G（2d，2p）密度泛函理论和FT-Raman研究3-（4-取代-苯基）-4,5-二氢-5-（4-取代-提出了苯基）吡唑-1-碳硫酰胺和3-（4-取代-苯基）-4,5-二氢-5-（4-取代-苯基）吡唑-1-羧酰胺。使用DFT将结构表征为势能表面中的最小值。计算得出的拉曼光谱和NMR光谱与实验结果非常吻合，因此已详细讨论了互变异构形式之间的平衡。我们的研究表明存在互变异构体，羧酰胺/碳硫酰胺基团可能以固态或溶液形式互变异构。计算得出的热力学数据表明，R（CS）NH2和R（C O）NH 2物种比R（C NH）SH和R（C NH）OH物种更稳定。此外，发现1 H NMR位移的结果指出存在哪种结构。