(Z)-3-(4-(4-hydroxy-3-methoxybenzylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid | 1225468-44-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-3-(4-(4-hydroxy-3-methoxybenzylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid
• 英文别名: 3-[(4Z)-4-[(4-hydroxy-3-methoxyphenyl)methylidene]-3-methyl-5-oxopyrazol-1-yl]benzoic acid
• CAS: 1225468-44-9
• 化学式: C₁₉H₁₆N₂O₅
• 分子量: 352.346
• InChiKey: NCPVLQFUTPGPOM-NVNXTCNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  99.4
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (Z)-3-(4-(4-hydroxy-3-methoxybenzylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid 、 2-溴丙烷 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 以65%的产率得到isopropyl (Z)-3-(4-(4-hydroxy-3-methoxybenzylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoate
  参考文献：
  名称：

  Discovery and Optimization of 1,3,4-Trisubstituted-pyrazolone Derivatives as Novel, Potent, and Nonsteroidal Farnesoid X Receptor (FXR) Selective Antagonists

  摘要：

  LBVS of 12480 in-house compounds, followed by HTRF assay, resulted in one nonsteroidal compound (11) with antagonistic activity against FXR (69.01 +/- 11.75 mu M). On the basis of 11, 26 new derivatives (12a-z) were designed and synthesized accordingly. Five derivatives (12f-g, 12p, 12u, and 12y) showed better antagonistic activities against FXR than compound 11. Remarkably, the most potent derivative, 12u (8.96 +/- 3.62 mu M), showed antagonistic capability approximately 10 times and 8-fold higher than that of the control (GS) and the starting compound 11, respectively. 12u was further confirmed to have high binding affinity with FXR alpha LBD, FXR specificity over six other nuclear receptors, and potent antagonistic activity against FXR in two cell testing platforms. 12u strongly suppressed the regulating effects of CDCA on FXR target genes. The therapeutic potential of 12u was identified by lowering the contents of triglyceride and cholesterol in human hepatoma HepG2 cells and in the cholesterol-fed C57BL/6 mices.

  DOI：

  10.1021/jm3002718
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 香草醛 、 3-肼基苯甲酸 反应 0.17h， 以68%的产率得到(Z)-3-(4-(4-hydroxy-3-methoxybenzylidene)-3-methyl-5-oxo-4,5-dihydro-1H-pyrazol-1-yl)benzoic acid
  参考文献：
  名称：

  在无溶剂条件下微波辅助一锅法合成吡唑啉酮衍生物。

  摘要：

  已经开发出一种高效的一锅法，可以在微波辐射和无溶剂条件下以 51-98% 的良好收率生成结构多样且具有药用价值的吡唑啉酮衍生物。

  DOI：

  10.3390/molecules15053593

文献信息

• Microwave-Assisted One-Pot Synthesis of Pyrazolone Derivatives under Solvent-Free Conditions
  作者：Ruoqun Ma、Jin Zhu、Jie Liu、Lili Chen、Xu Shen、Hualiang Jiang、Jian Li

  DOI：10.3390/molecules15053593

  日期：——

  An efficient one-pot method to generate structurally diverse and medicinally interesting pyrazolone derivatives in good to excellent yields of 51-98% under microwave irradiation and solvent-free conditions has been developed.

  已经开发出一种高效的一锅法，可以在微波辐射和无溶剂条件下以 51-98% 的良好收率生成结构多样且具有药用价值的吡唑啉酮衍生物。
• Discovery and Optimization of 1,3,4-Trisubstituted-pyrazolone Derivatives as Novel, Potent, and Nonsteroidal Farnesoid X Receptor (FXR) Selective Antagonists
  作者：Huang Huang、Ying Yu、Zhenting Gao、Yong Zhang、Chenjing Li、Xing Xu、Hui Jin、Wenzhong Yan、Ruoqun Ma、Jin Zhu、Xu Shen、Hualiang Jiang、Lili Chen、Jian Li

  DOI：10.1021/jm3002718

  日期：2012.8.23

  LBVS of 12480 in-house compounds, followed by HTRF assay, resulted in one nonsteroidal compound (11) with antagonistic activity against FXR (69.01 +/- 11.75 mu M). On the basis of 11, 26 new derivatives (12a-z) were designed and synthesized accordingly. Five derivatives (12f-g, 12p, 12u, and 12y) showed better antagonistic activities against FXR than compound 11. Remarkably, the most potent derivative, 12u (8.96 +/- 3.62 mu M), showed antagonistic capability approximately 10 times and 8-fold higher than that of the control (GS) and the starting compound 11, respectively. 12u was further confirmed to have high binding affinity with FXR alpha LBD, FXR specificity over six other nuclear receptors, and potent antagonistic activity against FXR in two cell testing platforms. 12u strongly suppressed the regulating effects of CDCA on FXR target genes. The therapeutic potential of 12u was identified by lowering the contents of triglyceride and cholesterol in human hepatoma HepG2 cells and in the cholesterol-fed C57BL/6 mices.