4-methylene-1,2-diphenyl-5-vinylpyrazolidin-3-one | 1609669-69-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: 4-methylene-1,2-diphenyl-5-vinylpyrazolidin-3-one
• 英文别名: 5-vinyl-1,2-diphenyl-4-methylenepyrazolidin-3-one；5-Ethenyl-4-methylidene-1,2-diphenylpyrazolidin-3-one
• CAS: 1609669-69-3
• 化学式: C₁₈H₁₆N₂O
• 分子量: 276.338
• InChiKey: GBLGOXZKOZDYLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  21
• 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：
  23.6
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  1,2-二苯肼 在 sodium hydride 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 84.0h， 生成 4-methylene-1,2-diphenyl-5-vinylpyrazolidin-3-one
  参考文献：
  名称：

  Anticancer Properties of Novel 4-methylene-1,2-diphenylpyrazolidin-3-ones

  摘要：

  The limited success of the currently used antitumor therapies is the driving force for organic chemists to seek new lead structures with anticancer potential. Two α‐methylene‐γ‐lactams with an additional nitrogen atom in the lactam ring, 5‐vinyl‐1,2‐diphenyl‐4‐methylenepyrazolidin‐3‐one (2a) and 5‐phenyl‐1,2‐diphenyl‐4‐methylenepyrazolidin‐3‐one (2b) have been synthesized. Their anticancer activity was assessed in MCF‐7 cells. Both compounds inhibited cell proliferation and induced DNA damage and apoptosis, with 2a being the more potent analog. Synergistic effects of 2a used in combination with known anticancer drugs, 5‐fluorouracil, taxol, and oxaliplatin were evaluated. Compound 2a significantly enhanced the antitumor action of oxaliplatin and 5‐fluorouracil, but not taxol.

  DOI：

  10.1111/cbdd.12565

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.