5-(4-nitrophenyl)-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole | 866261-43-0

• 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-nitrophenyl)-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole
• CAS: 866261-43-0
• 化学式: C₁₈H₁₇N₃O₅
• 分子量: 355.35
• InChiKey: QWSUIZWEQFBHNR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  102
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5-(4-nitrophenyl)-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole 在 palladium on activated charcoal 氢气 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以95%的产率得到4-[5-(3,4,5-Trimethoxy-phenyl)-2H-pyrazol-3-yl]-phenylamine
  参考文献：
  名称：

  Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins

  摘要：

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.028
• 作为产物：
  描述：

  (2E)-1-(3',4',5'-trimethoxyphenyl)-3-(4-nitrophenyl)-2-propen-1-one 在 双氧水 、 potassium carbonate 、 对甲苯磺酸 、 一水合肼 作用下， 以 甲醇 、 水 、 xylene 为溶剂， 反应 6.0h， 生成 5-(4-nitrophenyl)-3-(3,4,5-trimethoxyphenyl)-1H-pyrazole
  参考文献：
  名称：

  Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins

  摘要：

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.028

文献信息

• Heterocyclic analogs of combretastatin A-4
  作者：S. F. Vasilevsky、M. P. Davydova、G. A. Tolstikov

  DOI：10.1007/s10593-009-0171-4

  日期：2008.10

  A novel route is proposed for the synthesis of heterocyclic analogs of the naturally occurring combretastatin A-4 based on the reaction of alpha-acetylenic ketones with polyfunctional nucleophiles (hydroxylamine, hydrazine, guanidine). Previously unknown combretastatin A-4 analogs with azole and azine bridges were obtained.
• Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins
  作者：Regan LeBlanc、John Dickson、Toni Brown、Michelle Stewart、Hari N. Pati、Don VanDerveer、Hadi Arman、Jeff Harris、William Pennington、Herman L. Holt、Moses Lee

  DOI：10.1016/j.bmc.2005.06.028

  日期：2005.11

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.