ethyl 2-(3,4-bis(3,4-dimethoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)acetate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: ethyl 2-(3,4-bis(3,4-dimethoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)acetate
• 英文别名: Ethyl 2-[3,4-bis(3,4-dimethoxyphenyl)-2,5-dioxopyrrol-1-yl]acetate；ethyl 2-[3,4-bis(3,4-dimethoxyphenyl)-2,5-dioxopyrrol-1-yl]acetate
• 化学式: C₂₄H₂₅NO₈
• 分子量: 455.464
• InChiKey: UKSMBUXBDZNVKR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.56
• 重原子数：
  33.0
• 可旋转键数：
  9.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  100.6
• 氢给体数：
  0.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  (3,4-dimethoxy-phenyl)-acetic acid-(3,4-dimethoxy-phenacylamide) 在 potassium tert-butylate 、 sodium hydride 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 12.0h， 生成 ethyl 2-(3,4-bis(3,4-dimethoxyphenyl)-2,5-dioxo-2,5-dihydro-1H-pyrrole-1-yl)acetate
  参考文献：
  名称：

  Structure–Activity Relationship Study of Permethyl Ningalin B Analogues as P-Glycoprotein Chemosensitizers

  摘要：

  A novel series of permethyl ningalin B analogues were synthesized and evaluated for their P-glycoprotein (P-gp)-modulating activities in a P-gp-overexpressing breast cancer cell line (LCC6MDR). Compounds 35 and 37, which possess one methoxy group and one benzyloxy group at aryl ring C, displayed the most potent Pgp-modulating activity. A 1 pM concentration of 35 and 37 resensitized LCC6MDR cells toward paclitaxel by 42.7-fold, with respective EC50 values of 93.5 and 110.0 nM. Their mechanism of P-gp modulation is associated with an increase in intracellular drug accumulation. Their advantages also include low cytotoxicity (IC50 for L929 fibroblast >100 mu M) and high therapeutic indexes (>909 after normalization with their EC50 values). 35 is not a substrate of P-gp. They are potentially dual-selective modulators for both P-gp and breast cancer resistance protein transporters. The present study demonstrates that these new compounds can be employed as effective and safe modulators of Pgp-mediated drug resistance in cancer cells.

  DOI：

  10.1021/jm400930e

文献信息

• Structure–Activity Relationship Study of Permethyl Ningalin B Analogues as P-Glycoprotein Chemosensitizers
  作者：Jin Wen Bin、Iris L. K. Wong、Xuesen Hu、Zhang Xiao Yu、Li Fu Xing、Tao Jiang、Larry M. C. Chow、Wan Sheng Biao

  DOI：10.1021/jm400930e

  日期：2013.11.27

  A novel series of permethyl ningalin B analogues were synthesized and evaluated for their P-glycoprotein (P-gp)-modulating activities in a P-gp-overexpressing breast cancer cell line (LCC6MDR). Compounds 35 and 37, which possess one methoxy group and one benzyloxy group at aryl ring C, displayed the most potent Pgp-modulating activity. A 1 pM concentration of 35 and 37 resensitized LCC6MDR cells toward paclitaxel by 42.7-fold, with respective EC50 values of 93.5 and 110.0 nM. Their mechanism of P-gp modulation is associated with an increase in intracellular drug accumulation. Their advantages also include low cytotoxicity (IC50 for L929 fibroblast >100 mu M) and high therapeutic indexes (>909 after normalization with their EC50 values). 35 is not a substrate of P-gp. They are potentially dual-selective modulators for both P-gp and breast cancer resistance protein transporters. The present study demonstrates that these new compounds can be employed as effective and safe modulators of Pgp-mediated drug resistance in cancer cells.