(7-isopropoxy-4-methyl-2-oxo-2H-chromen-8-yl)methyl 2,4,5-trimethoxybenzoate

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 英文名称: (7-isopropoxy-4-methyl-2-oxo-2H-chromen-8-yl)methyl 2,4,5-trimethoxybenzoate
• 英文别名: (4-Methyl-2-oxo-7-propan-2-yloxychromen-8-yl)methyl 2,4,5-trimethoxybenzoate；(4-methyl-2-oxo-7-propan-2-yloxychromen-8-yl)methyl 2,4,5-trimethoxybenzoate
• 化学式: C₂₄H₂₆O₈
• 分子量: 442.466
• InChiKey: MLABGCIWPMSOLA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  89.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  7-isopropoxy-4-methyl-2-oxo-2H-chromen-8-carbaldehyde 在 4-二甲氨基吡啶 、 sodium tetrahydroborate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (7-isopropoxy-4-methyl-2-oxo-2H-chromen-8-yl)methyl 2,4,5-trimethoxybenzoate
  参考文献：
  名称：

  Seco-4-methyl-DCK derivatives as potent chemosensitizers

  摘要：

  Twenty-five seco-4-methyl-DCK derivatives were designed, synthesized and evaluated for chemoreversal activity when combined with paclitaxel or vincristine in two drug-resistant cancer cell lines (A2780/T and KB-V) respectively. Most of the new compounds displayed moderate to significant MDR reversal activities in the P-gp overexpressing A2780/T and KB-V cells. Especially, compounds 7o and 7y showed the most potent chemosensitization activities with more than 496 and 735 reversal ratios at a concentration of 10 mu M. Unexpectedly the newly synthesized compounds did not show chemosensitization activities observed in a non-P-gp overexpressing cisplatin resistant human ovarian cancer cell line (A2780/CDDP), implying that the MDR reversal effects might be associated with P-gp overexpression. Moreover, these compounds did not exhibit significant antiproliferative activities against nontumorigenic cell lines (HUVEC, HOSEC and T29) compared to the positive control verapamil at the tested concentration, which suggested better safety than verapamil. The pharmacological actions of the compounds will be studied further to explore their merit for development as novel candidates to overcome P-gp mediated MDR cancer.

  DOI：

  10.1016/j.bmcl.2018.11.023

文献信息

• Seco-4-methyl-DCK derivatives as potent chemosensitizers
  作者：Yalan Guo、Ke Wang、Xiaoyu Chen、Haihong Li、Qi Wan、Susan Morris-Natschke、Kuo-Hsiung Lee、Ying Chen

  DOI：10.1016/j.bmcl.2018.11.023

  日期：2019.1

  Twenty-five seco-4-methyl-DCK derivatives were designed, synthesized and evaluated for chemoreversal activity when combined with paclitaxel or vincristine in two drug-resistant cancer cell lines (A2780/T and KB-V) respectively. Most of the new compounds displayed moderate to significant MDR reversal activities in the P-gp overexpressing A2780/T and KB-V cells. Especially, compounds 7o and 7y showed the most potent chemosensitization activities with more than 496 and 735 reversal ratios at a concentration of 10 mu M. Unexpectedly the newly synthesized compounds did not show chemosensitization activities observed in a non-P-gp overexpressing cisplatin resistant human ovarian cancer cell line (A2780/CDDP), implying that the MDR reversal effects might be associated with P-gp overexpression. Moreover, these compounds did not exhibit significant antiproliferative activities against nontumorigenic cell lines (HUVEC, HOSEC and T29) compared to the positive control verapamil at the tested concentration, which suggested better safety than verapamil. The pharmacological actions of the compounds will be studied further to explore their merit for development as novel candidates to overcome P-gp mediated MDR cancer.