2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-chlorobenzoate | 1281816-39-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-chlorobenzoate
• 英文别名: [2-[2-(4-Chlorophenyl)-6,6-dimethyl-1-phenyl-5,7-dihydropyrrolizin-3-yl]-2-oxoethyl] 4-chlorobenzoate
• CAS: 1281816-39-4
• 化学式: C₃₀H₂₅Cl₂NO₃
• 分子量: 518.439
• InChiKey: KTQIOOGNCMQVFZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  48.3
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  3,3-dimethyl-4-hydroxy butyronitrile 在 吡啶 、 氯化亚砜 、 三氟化硼乙醚 、 碳酸氢钠 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 丙酮 为溶剂， 反应 65.25h， 生成 2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl 4-chlorobenzoate
  参考文献：
  名称：

  Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives

  摘要：

  A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (81) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.01.002

文献信息

• Investigations on cytotoxicity and anti-inflammatory potency of licofelone derivatives
  作者：Wukun Liu、Jinpei Zhou、Kerstin Bensdorf、Huibin Zhang、Haoran Liu、Yubin Wang、Hai Qian、Yanchun Zhang、Anja Wellner、Gerhard Rubner、Wenlong Huang、Cancheng Guo、Ronald Gust

  DOI：10.1016/j.ejmech.2011.01.002

  日期：2011.3

  A series of C5-substituted licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3-dihydro-1H-pyrrolizin-5-yl]acetic acid) derivatives were developed by a parallel synthesis approach and investigated for cytotoxicity against MCF-7 and MDA-MB-231 cells as well as for anti-inflammatory potency in vitro and in vivo. Dependent on the C5-substituent, the compounds showed high selectivity for MCF-7 cells. Especially 2-oxoethyl benzoate derivatives were inactive at the MDA-MB-231 cell line and as active as 5-FU at MCF-7 cells. C5-acetyl (8a), -2-oxoethyl formiate (8e), -2-oxoethyl acetate (81) and -2-oxoethyl propionate (8g) derivatives showed growth inhibition at both cell lines, comparable with cisplatin. Modifications significantly reduced the inhibitory potency at COX-1 and COX-2 in vitro and in the xylene-induced ear swelling assay in mice. Only compound 8a was equipotent to licofelone, ibuprofen and celecoxibe in vivo. (C) 2011 Elsevier Masson SAS. All rights reserved.