2-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone | 1281816-34-9

• 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-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone
• 英文别名: 2-Chloro-1-[2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-5,7-dihydropyrrolizin-3-yl]ethanone
• CAS: 1281816-34-9
• 化学式: C₂₃H₂₁Cl₂NO
• 分子量: 398.332
• InChiKey: VTCFHPGALJKULJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  22
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone 、 丙酸 在 三乙胺 作用下， 以 丙酮 为溶剂， 反应 24.25h， 以95.1%的产率得到2-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)-2-oxoethyl propionate
  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
• 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 作用下， 以 乙醚 、 乙醇 为溶剂， 反应 41.0h， 生成 2-chloro-1-(2-(4-chlorophenyl)-6,6-dimethyl-1-phenyl-6,7-dihydro-5H-pyrrolizin-3-yl)ethanone
  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

• Synthesis and Biological Evaluation of Licofelone Derivatives as Anticancer and Anti-inflammatory Agents
  作者：Wukun Liu、Jinpei Zhou、Huibin Zhang、Hai Qian、Jiahan Yin、Kerstin Bensdorf、Ronald Gust

  DOI：10.2174/157018011797655223

  日期：2011.12.1

  Two C5-substituted licofelone derivatives were developed and investigated for cytotoxicity against mammary (MCF-7 and MDA-MB 231) as well as colon carcinoma (HT-29) cancer cells. Both compounds were at least 2-fold more active than 5-fluorouracil (5-FU) and licofelone against mammary carcinoma cells. At HT-29 cells, they were less active, but nevertheless distinctly as active as 5-FU and still 2-fold more active than licofelone. However, variation of the C5- carboxylic group results in an occasionally remarkable decrease of anti-inflammatory potency in in vitro and in vivo.

  研究人员开发了两种 C5 取代的利可非酮衍生物，并研究了它们对乳腺癌细胞（MCF-7 和 MDA-MB 231）以及结肠癌细胞（HT-29）的细胞毒性。这两种化合物对乳腺癌细胞的活性至少是 5-氟尿嘧啶（5-FU）和利可非酮的 2 倍。在 HT-29 细胞中，这两种化合物的活性较低，但与 5-FU 的活性相当，仍比利可非酮高出 2 倍。不过，C5-羧基的变化偶尔会导致体外和体内抗炎效力的显著下降。