4-[(4-acetylanilino)methylidene]-5-methyl-2-phenylpyrazol-3-one

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[(4-acetylanilino)methylidene]-5-methyl-2-phenylpyrazol-3-one
• 化学式: C₁₉H₁₇N₃O₂
• mdl: MFCD00819244
• 分子量: 319.4
• InChiKey: HNUOEUITWDCQQZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 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：
  61.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[(4-acetylanilino)methylidene]-5-methyl-2-phenylpyrazol-3-one 在 sodium acetate 、 溶剂黄146 作用下， 以 1,4-二氧六环 、 乙醇 为溶剂， 反应 12.0h， 生成 3-benzyl-2-((1-(4-(((3-methyl-5-oxo-1-phenyl-1,5-dihydro-4H-pyrazol-4-ylidene)methyl)amino)phenyl)ethylidene)hydrazineylidene)thiazolidin-4-one
  参考文献：
  名称：

  10.1002/jhet.4858

  摘要：

  AbstractIn this research article, the chemical synthesis of new N‐phenylpyrazolone‐N‐benzylthiazole hybrids (3–6) via late‐stage thiazolation of the corresponding benzylthiosemicarbazone 2 was reported. The skeletal structural of the new molecules were validated by instrumental measurements (FT‐IR, NMR, and EI‐MS). In vitro cytotoxicity‐based cellular MTT bioassay shows that compound 3 that bears an N‐benzyl‐4‐thiazolone moiety is the most potent one toward the osteosarcoma cell line (Hos) with an IC50 value of 5.8 ± 0.1 μM, while compound 4a that contains a 5‐acetyl‐N‐benzylthiazole unit is the most robust one against the model lung carcinoma cell line (A549) with an IC50 value of 9.23 ± 0.01 μM. Also, 3 is roughly equipotent to 4b in its cytotoxicity activity against A549. In vitro enzymatic ELISA bioassay of A549 cells indicates that IC50 of 3 caused a decrease in the pRIPK3 kinase concentration (2.89 ± 0.005 pg/mL) as compared to DMSO‐treated cells (2.93 ± 0.010 pg/mL), while the pRIPK3 level incresed with 4b impact. As a result, 3 may be an effective inhibitor of pRIPK3 and hence necroptosis, proposing a novel therapeutic strategy for necroptosis‐related illnesses. In silico molecular docking shows that 3 interlocked and fitted well into the binding site of RIPK3 (PDB code: 7MX3) with a fitness value (−123.382 kcal/mol) lower than 4b and forms an important H‐bond with Lys50 like the marketed RIPK3 inhibitor GSK'843, validating the experimental results. Consequently, 3 is the most promising molecule that could be a lead candidate for further studies.

  DOI：

  10.1002/jhet.4858
• 作为产物：
  描述：

  苯肼 在 原甲酸三乙酯 作用下， 以 乙醇 为溶剂， 反应 7.0h， 生成 4-[(4-acetylanilino)methylidene]-5-methyl-2-phenylpyrazol-3-one
  参考文献：
  名称：

  10.1002/jhet.4858

  摘要：

  AbstractIn this research article, the chemical synthesis of new N‐phenylpyrazolone‐N‐benzylthiazole hybrids (3–6) via late‐stage thiazolation of the corresponding benzylthiosemicarbazone 2 was reported. The skeletal structural of the new molecules were validated by instrumental measurements (FT‐IR, NMR, and EI‐MS). In vitro cytotoxicity‐based cellular MTT bioassay shows that compound 3 that bears an N‐benzyl‐4‐thiazolone moiety is the most potent one toward the osteosarcoma cell line (Hos) with an IC50 value of 5.8 ± 0.1 μM, while compound 4a that contains a 5‐acetyl‐N‐benzylthiazole unit is the most robust one against the model lung carcinoma cell line (A549) with an IC50 value of 9.23 ± 0.01 μM. Also, 3 is roughly equipotent to 4b in its cytotoxicity activity against A549. In vitro enzymatic ELISA bioassay of A549 cells indicates that IC50 of 3 caused a decrease in the pRIPK3 kinase concentration (2.89 ± 0.005 pg/mL) as compared to DMSO‐treated cells (2.93 ± 0.010 pg/mL), while the pRIPK3 level incresed with 4b impact. As a result, 3 may be an effective inhibitor of pRIPK3 and hence necroptosis, proposing a novel therapeutic strategy for necroptosis‐related illnesses. In silico molecular docking shows that 3 interlocked and fitted well into the binding site of RIPK3 (PDB code: 7MX3) with a fitness value (−123.382 kcal/mol) lower than 4b and forms an important H‐bond with Lys50 like the marketed RIPK3 inhibitor GSK'843, validating the experimental results. Consequently, 3 is the most promising molecule that could be a lead candidate for further studies.

  DOI：

  10.1002/jhet.4858