4β-N-(2",4"-dimethoxyphenylsulfonylurea)-4-deoxyanhydroepipodophyllotoxin | 1531622-94-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 四氢化萘
• 英文名称: 4β-N-(2",4"-dimethoxyphenylsulfonylurea)-4-deoxyanhydroepipodophyllotoxin
• 英文别名: 1-[(5S,5aS,8aR,9R)-9-(3,4,5-trimethoxyphenyl)-5,5a,6,8,8a,9-hexahydro-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]-3-(2,4-dimethoxyphenyl)sulfonylurea
• CAS: 1531622-94-2
• 化学式: C₃₁H₃₄N₂O₁₁S
• 分子量: 642.684
• InChiKey: XUISQLFLBRSONN-KDOVTMOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  45
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  [(5R,6R,7R,8R)-8-(tert-Butyl-dimethyl-silanyloxy)-7-hydroxymethyl-5-(3,4,5-trimethoxy-phenyl)-5,6,7,8-tetrahydro-naphtho[2,3-d][1,3]dioxol-6-yl]-methanol 在 三氟化硼乙醚 、 四丁基氟化铵 、 氨 、 钯 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙酸乙酯 、 甲苯 、 苯 为溶剂， 生成 4β-N-(2",4"-dimethoxyphenylsulfonylurea)-4-deoxyanhydroepipodophyllotoxin
  参考文献：
  名称：

  Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin

  摘要：

  Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC50: 1.41-1.76 mu M) and 14e (IC50: 1.72-2.01 mu M) showed superior cytotoxic activity compared with etoposide (IC50: 2.03 to >20 mu M), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4'-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin's 4 beta position can significantly improve cytotoxic activity. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.11.035

文献信息

• Design, synthesis and cytotoxic activity of novel sulfonylurea derivatives of podophyllotoxin
  作者：Zhi-Jun Zhang、Jing Tian、Li-Ting Wang、Mei-Juan Wang、Xiang Nan、Liu Yang、Ying-Qian Liu、Susan L. Morris-Natschke、Kuo-Hsiung Lee

  DOI：10.1016/j.bmc.2013.11.035

  日期：2014.1

  Three series of novel sulfonylurea podophyllotoxin derivatives were designed, synthesized, and evaluated for in vitro cytotoxicity against four tumor cell lines (A-549, DU-145, KB and KBvin). Compounds 14c (IC50: 1.41-1.76 mu M) and 14e (IC50: 1.72-2.01 mu M) showed superior cytotoxic activity compared with etoposide (IC50: 2.03 to >20 mu M), a clinically available anticancer drug. Significantly, most of the compounds exhibited comparable cytotoxicity against the drug-resistant tumor cell line KBvin, while etoposide lost activity completely. Preliminary structure-activity relationship (SAR) correlations indicated that the 4'-O-methyl functionality in podophyllotoxin analogues may be essential to maintain cytotoxic activity, while an arylsulfonylurea side chain at podophyllotoxin's 4 beta position can significantly improve cytotoxic activity. (C) 2013 Elsevier Ltd. All rights reserved.