Dimethylamino-acetic acid 2,6-dimethoxy-4-[(5R,5aR,8aS,9S)-9-(4-nitro-phenylamino)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-phenyl ester

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 木脂素内酯
• 英文名称: Dimethylamino-acetic acid 2,6-dimethoxy-4-[(5R,5aR,8aS,9S)-9-(4-nitro-phenylamino)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-phenyl ester
• 英文别名: [4-[(5S,5aS,8aR,9R)-5-(4-nitroanilino)-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-9-yl]-2,6-dimethoxyphenyl] 2-(dimethylamino)acetate
• 化学式: C₃₁H₃₁N₃O₁₀
• 分子量: 605.601
• InChiKey: DXOGCBIIWOEZRW-MHTDFPPDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  151
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  N,N-二甲基甘氨酸 、 4'-O-demethyl-4β-(4''-nitroanilino)-4-desoxypodophyllotoxin 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以90%的产率得到Dimethylamino-acetic acid 2,6-dimethoxy-4-[(5R,5aR,8aS,9S)-9-(4-nitro-phenylamino)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-phenyl ester
  参考文献：
  名称：

  Antitumor agents. Part 235: Novel 4′-ester etoposide analogues as potent DNA topoisomerase II inhibitors with improved therapeutic potential

  摘要：

  Eight 4'-ester epipodophyllotoxin derivatives (9-16) were designed and synthesized with the aim to overcome drug-resistance and improve water-solubility simultaneously. These compounds were superior to etoposide (1) in causing cellular proteinlinked DNA breaks and inhibiting KB and 1-resistant KB-7d cell replication. Compounds 9 and 10 showed significant inhibitory activity against DNA topoisomerase 11 in vitro. Compound 10 also exhibited an in vitro DNA cleavage pattern similar to that of GL-331 (5). A hypothetical model on the action mode of 1-analogues is proposed based on the results. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.03.056

文献信息

• Antitumor agents. Part 235: Novel 4′-ester etoposide analogues as potent DNA topoisomerase II inhibitors with improved therapeutic potential
  作者：Zhiyan Xiao、John R Vance、Kenneth F Bastow、Arnold Brossi、Hui-Kang Wang、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2004.03.056

  日期：2004.6

  Eight 4'-ester epipodophyllotoxin derivatives (9-16) were designed and synthesized with the aim to overcome drug-resistance and improve water-solubility simultaneously. These compounds were superior to etoposide (1) in causing cellular proteinlinked DNA breaks and inhibiting KB and 1-resistant KB-7d cell replication. Compounds 9 and 10 showed significant inhibitory activity against DNA topoisomerase 11 in vitro. Compound 10 also exhibited an in vitro DNA cleavage pattern similar to that of GL-331 (5). A hypothetical model on the action mode of 1-analogues is proposed based on the results. (C) 2004 Elsevier Ltd. All rights reserved.