5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde | 1312886-47-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde
• 英文别名: 5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)pyrazole-4-carbaldehyde
• CAS: 1312886-47-7
• 化学式: C₁₇H₁₀ClF₃N₂O
• 分子量: 350.727
• InChiKey: YEBAWYVHPNUTJE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  34.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde 、 对氯苯乙酮 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 6.0h， 以40%的产率得到1-(4-chlorophenyl)-3-(5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl)prop-2-en-1-one
  参考文献：
  名称：

  Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study

  摘要：

  New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC50 value of 0.45 mu M and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2011.04.027
• 作为产物：
  描述：

  1-(4-氯苯基)-4,4,4-三氟丁烷-1,3-二酮 在 硫酸 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 生成 5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde
  参考文献：
  名称：

  吡唑和吡唑啉衍生物作为选择性COX-2抑制剂和抗炎药的合成，生物学评估和分子建模研究。第2部分

  摘要：

  已经合成了新的吡唑和吡唑啉衍生物，并使用体外环氧合酶（COX）抑制试验评估了它们抑制绵羊COX-1 / COX-2同工酶的能力。在测试的化合物中，N -（（5-（4-氯苯基）-1-苯基-3-（三氟甲基）-1 H-吡唑-4-基）亚甲基）-3,5-双（三氟甲基）苯胺8d表现出最佳COX-2抑制效能（IC 50  = 0.26 lM）和选择性（SI）=> 192.3]与参考药物塞来昔布（IC 50值为0.28 lM，选择性指数为178.57）。此外，使用角叉菜胶诱导的大鼠爪水肿模型在体内研究了所选化合物的抗炎活性，该化合物是COX抑制测定中最具选择性的COX-2抑制剂。进行了分子建模以研究活性化合物结合到COX-2活性位点的能力，该能力揭示了与选择性COX-2抑制剂SC-558相似的结合模式。

  DOI：

  10.1016/j.bmc.2012.03.044

文献信息

• Antitumor evaluation and molecular docking study of substituted 2-benzylidenebutane-1,3-dione, 2-hydrazonobutane-1,3-dione and trifluoromethyl-1H-pyrazole analogues
  作者：Ibrahim A. Al-Suwaidan、Naglaa I. Abdel-Aziz、Adel S. El-Azab、Magda A.-A. El-Sayed、Amer M. Alanazi、Mahmoud B. El-Ashmawy、Alaa A.-M. Abdel-Aziz

  DOI：10.3109/14756366.2014.960863

  日期：2015.7.4

  A series of 2-(arylidene)-1-(4-chlorophenyl)-4,4,4-trifluorobutane-1,3-diones (2-4), 4-(arylidene)-3-(4-chlorophenyl)-5-(trifluoromethyl)-4H-pyrazoles (5-7), 1-(4-chlorophenyl)-4,4,4-trifluoro-2-( 2-(aryl) hydrazono) butane-1,3-diones (8, 9), 3-(4-chlorophenyl)-4-(2-(aryl) hydrazono)-5-(trifluoromethyl)-4H-pyrazoles (10, 11), 2-((3-(4-chlorophenyl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazol4-yl) methylene) malononitrile (13), 2-((5-(4-chlorophenyl)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-4-yl) methylene) cycloalkan-1-ones (14, 15) and 1-(aryl)-3-(5-(4-chlorophenyl)-1-phenyl-3-( trifluoromethyl)-1H-pyrazol-4-yl) prop-2-en-1-ones (16, 17) were designed, synthesized and evaluated for their in vitro antitumor activity. 1-(4-Chlorophenyl)-4,4,4-trifluoro-2-(2-(4-methoxyphenyl) hydrazono) butane-1,3-dione (8) showed potential and broad spectrum antitumor activity compared to the known drug 5-FU with GI(50,) (6.61 and 22.60 mu M), TGI (42.66 and <100 mu M) and LC50 (93.33 and <100 mu M) values, respectively. On the other hand, compound 8 yielded selective activities toward melanoma, colon, non-small lung and breast cancer cell lines compared with erlotinib and gefitinib. Molecular docking methodology was performed for compound 8 into binding site of B-RAFV600E and EGFR kinases which showed similar binding mode to vemurafenib (PLX4032) and erlotinib, respectively.
• Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2
  作者：Magda A.-A. El-Sayed、Naglaa I. Abdel-Aziz、Alaa A.-M. Abdel-Aziz、Adel S. El-Azab、Kamal E.H. ElTahir

  DOI：10.1016/j.bmc.2012.03.044

  日期：2012.5

  anti-inflammatory activity of selected compounds, which are the most selective COX-2 inhibitors in the COX inhibition assay, was investigated in vivo using carrageenan-induced rat paw edema model. Molecular modeling was conducted to study the ability of the active compounds to bind into the active site of COX-2 which revealed a similar binding mode to SC-558, a selective COX-2 inhibitor.

  已经合成了新的吡唑和吡唑啉衍生物，并使用体外环氧合酶（COX）抑制试验评估了它们抑制绵羊COX-1 / COX-2同工酶的能力。在测试的化合物中，N -（（5-（4-氯苯基）-1-苯基-3-（三氟甲基）-1 H-吡唑-4-基）亚甲基）-3,5-双（三氟甲基）苯胺8d表现出最佳COX-2抑制效能（IC 50  = 0.26 lM）和选择性（SI）=> 192.3]与参考药物塞来昔布（IC 50值为0.28 lM，选择性指数为178.57）。此外，使用角叉菜胶诱导的大鼠爪水肿模型在体内研究了所选化合物的抗炎活性，该化合物是COX抑制测定中最具选择性的COX-2抑制剂。进行了分子建模以研究活性化合物结合到COX-2活性位点的能力，该能力揭示了与选择性COX-2抑制剂SC-558相似的结合模式。
• Design, synthesis, and biological evaluation of substituted hydrazone and pyrazole derivatives as selective COX-2 inhibitors: Molecular docking study
  作者：Magda A.-A. El-Sayed、Naglaa I. Abdel-Aziz、Alaa A.-M. Abdel-Aziz、Adel S. El-Azab、Yousif A. Asiri、Kamal E.H. ElTahir

  DOI：10.1016/j.bmc.2011.04.027

  日期：2011.6

  New arylhydrazone derivatives and a series of 1,5-diphenyl pyrazoles were designed and synthesized from 1-(4-chlorophenyl)-4,4,4-trifuorobutane-1,3-dione 1. The newly synthesized compounds were investigated in vivo for their anti-inflammatory activities using carrageenan-induced rat paw oedema model. Moreover, they were tested for their inhibitory activity against ovine COX-1 and COX-2 using an in vitro cyclooxygenase (COX) inhibition assay. Some of the new compounds (2f, 6a and 6d) showed a reasonable in vitro COX-2 inhibitory activity, with IC50 value of 0.45 mu M and selectivity index of 111.1. A virtual screening was carried out through docking the designed compounds into the COX-2 binding site to predict if these compounds have analogous binding mode to the COX-2 inhibitors. Docking study of the synthesized compounds 2f, 6a and 6d into the active site of COX-2 revealed a similar binding mode to SC-558, a selective COX-2 inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.