5-ethyl-1-methyl-4-methylidene-2-phenylpyrazolidin-3-one | 1609669-60-4

• 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: 5-ethyl-1-methyl-4-methylidene-2-phenylpyrazolidin-3-one
• 英文别名: 5-Ethyl-1-methyl-4-methylidene-2-phenylpyrazolidin-3-one
• CAS: 1609669-60-4
• 化学式: C₁₃H₁₆N₂O
• 分子量: 216.283
• InChiKey: VGRLHUXESUIKEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  diethyl (5-ethyl-1-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)phosphonate 在 L-Selectride 、 sodium hydride 作用下， 以 四氢呋喃 、 mineral oil 为溶剂， 反应 21.5h， 生成 5-ethyl-1-methyl-4-methylidene-2-phenylpyrazolidin-3-one
  参考文献：
  名称：

  Design, synthesis and cytotoxic evaluation of 4-methylidenepyrazolidin-3-ones

  摘要：

  Three series of new 4-methylidenepyrazolidin-3-ones with various substitution patterns were synthesized and tested for the cytotoxic activity against two human leukemia cell lines NALM-6 and HL-60 as well as MCF-7 breast cancer cell line. Several obtained methylidenepyrazolidinones exhibited high cytotoxic activity with IC50 values below 10 mu M, mainly against HL-60 leukemia cell line and two of them, 18d,e, displayed IC50 <= 5 mu M, against all tested cell lines. Structure activity relationship studies revealed that the presence of phenyl substituents on both ring nitrogen atoms and vinyl or phenyl substituents in position 5 are crucial for high activity. Selected methylidenepyrazolidinones were also tested on normal human umbilical vein endothelial cells (HUVEC) and pyrazolidinone 18a was found to be 5-fold more toxic against HL-60 than normal cells. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.01.029

文献信息

• Versatile Synthesis of 4-Methylidenepyrazolidin-3-ones Using a Horner–Wadsworth–Emmons Approach
  作者：Tomasz Janecki、Jakub Modranka、Rafał Jakubowski

  DOI：10.1055/s-0033-1340071

  日期：——

  A new, versatile method for the synthesis of, so far unknown, variously substituted 4-methylidenepyrazolidin-3-ones as potential cytotoxic agents is described. Target compounds were synthesized from the corresponding 4-diethoxyphosphorylpyrazolidin-3-ones which were used as Horner-Wadsworth-Emmons reagents for the olefination of formaldehyde. 4-Phosphorylpyrazolidin-3-ones were, in turn, obtained starting from the sodium salt of ethyl 2-diethoxyphosphoryl-3-hydroxy-2-propenoate, ethyl 2-acyl-2-diethoxyphosphorylacetates, or 3-methoxy-2-diethoxyphosphorylacrylate and monosubstituted or 1,2-disubstituted hydrazines.
• Design, synthesis and cytotoxic evaluation of 4-methylidenepyrazolidin-3-ones
  作者：Jakub Modranka、Rafał Jakubowski、Marek Różalski、Urszula Krajewska、Anna Janecka、Katarzyna Gach、Dorota Pomorska、Tomasz Janecki

  DOI：10.1016/j.ejmech.2015.01.029

  日期：2015.3

  Three series of new 4-methylidenepyrazolidin-3-ones with various substitution patterns were synthesized and tested for the cytotoxic activity against two human leukemia cell lines NALM-6 and HL-60 as well as MCF-7 breast cancer cell line. Several obtained methylidenepyrazolidinones exhibited high cytotoxic activity with IC50 values below 10 mu M, mainly against HL-60 leukemia cell line and two of them, 18d,e, displayed IC50 <= 5 mu M, against all tested cell lines. Structure activity relationship studies revealed that the presence of phenyl substituents on both ring nitrogen atoms and vinyl or phenyl substituents in position 5 are crucial for high activity. Selected methylidenepyrazolidinones were also tested on normal human umbilical vein endothelial cells (HUVEC) and pyrazolidinone 18a was found to be 5-fold more toxic against HL-60 than normal cells. (C) 2015 Elsevier Masson SAS. All rights reserved.