4'-O-脱甲基-4-((4'-(1'-苯甲基哌啶基))氨基)-4-脱氧鬼臼毒 | 152833-13-1

• 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
• 中文名称: 4'-O-脱甲基-4-((4'-(1'-苯甲基哌啶基))氨基)-4-脱氧鬼臼毒
• 英文名称: 4'-O-demethyl-4β-{[4''-(1''-benzylpiperidinyl)]amino}-4-desoxypodophyllotoxin
• 英文别名: Dbadptx；(5S,5aS,8aR,9R)-5-[(1-benzylpiperidin-4-yl)amino]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one
• CAS: 152833-13-1
• 化学式: C₃₃H₃₆N₂O₇
• 分子量: 572.658
• InChiKey: GQMFUALQPLOONU-QIXIFPRPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  42
• 可旋转键数：
  7
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4'-去甲基表鬼臼毒素 在 氢溴酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.0h， 生成 4'-O-脱甲基-4-((4'-(1'-苯甲基哌啶基))氨基)-4-脱氧鬼臼毒
  参考文献：
  名称：

  Antitumor Agents. 148. Synthesis and Biological Evaluation of Novel 4.beta.-Amino Derivatives of Etoposide with Better Pharmacological Profiles

  摘要：

  A series of novel 4 beta-amino derivatives of etoposide (1), which can form water-soluble salts and demonstrate excellent activity against mdr- and topo II-resistant cell lines, have been synthesized. Compared with etoposide; compounds 5-6, 8, and 10-16 show comparable or greater inhibition of human DNA topo II. In a cellular protein-DNA complex formation assay, compounds 5-6, 8, 10-14, and 16 are more potent than 1. A dose-response study of 8 shows that it is 20 times more active in formation of protein-linked DNA breaks than etoposide. Furthermore, both 8 and its free base 7 were found to be highly active toward etoposide-resistant KB cell lines. All compounds were also evaluated in vitro against a total of 56 human tumor cell lines derived from seven cancer types. Comparison of the log(10) GI(50) mean graph midpoints of 5-19 (-4.89 to -7.30) with that of 1 (-4.08) shows these new analogs to be 6-1659-fold more active than 1.

  DOI：

  10.1021/jm00030a003

文献信息

• Antitumor Agents. 148. Synthesis and Biological Evaluation of Novel 4.beta.-Amino Derivatives of Etoposide with Better Pharmacological Profiles
  作者：Yi Lin Zhang、Xin Guo、Yung Chi Cheng、Kuo Hsiung Lee

  DOI：10.1021/jm00030a003

  日期：1994.2

  A series of novel 4 beta-amino derivatives of etoposide (1), which can form water-soluble salts and demonstrate excellent activity against mdr- and topo II-resistant cell lines, have been synthesized. Compared with etoposide; compounds 5-6, 8, and 10-16 show comparable or greater inhibition of human DNA topo II. In a cellular protein-DNA complex formation assay, compounds 5-6, 8, 10-14, and 16 are more potent than 1. A dose-response study of 8 shows that it is 20 times more active in formation of protein-linked DNA breaks than etoposide. Furthermore, both 8 and its free base 7 were found to be highly active toward etoposide-resistant KB cell lines. All compounds were also evaluated in vitro against a total of 56 human tumor cell lines derived from seven cancer types. Comparison of the log(10) GI(50) mean graph midpoints of 5-19 (-4.89 to -7.30) with that of 1 (-4.08) shows these new analogs to be 6-1659-fold more active than 1.