(5S,5aS,8aR,9R)-5-[(4-氟苯基)氨基]-9-(4-羟基-3,5-二甲氧基-苯基)-5a,6,8a,9-四氢-5H-异苯并呋喃并[5,6-f][1,3]苯并二氧戊环-8-酮 | 125830-36-6

• 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: (5S,5aS,8aR,9R)-5-[(4-氟苯基)氨基]-9-(4-羟基-3,5-二甲氧基-苯基)-5a,6,8a,9-四氢-5H-异苯并呋喃并[5,6-f][1,3]苯并二氧戊环-8-酮
• 中文别名: 2-氨基-5-溴-6-(3-氟苯基)嘧啶-4(1H)-酮
• 英文名称: 4'-demethyl-4-p-fluoroaniline-4-desoxypodophyllotoxin
• 英文别名: 4'-demethyl-4β-(4"-fluoroanilino)-4-desoxypodophyllotoxin；4'-O-demethyl-4β-(4''-fluoroanilino)-4-desoxypodophyllotoxin；NFP；Npf-etoposide；(5S,5aS,8aR,9R)-5-(4-fluoroanilino)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 125830-36-6
• 化学式: C₂₇H₂₄FNO₇
• 分子量: 493.488
• InChiKey: OWZJVOYADMZDSO-LVEBQJTPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  36
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (5S,5aS,8aR,9R)-5-[(4-氟苯基)氨基]-9-(4-羟基-3,5-二甲氧基-苯基)-5a,6,8a,9-四氢-5H-异苯并呋喃并[5,6-f][1,3]苯并二氧戊环-8-酮 在 4-二甲氨基吡啶 、 对甲苯磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 (S)-2-Amino-propionic acid 4-[(5R,5aR,8aS,9S)-9-(4-fluoro-phenylamino)-6-oxo-5,5a,6,8,8a,9-hexahydro-furo[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl]-2,6-dimethoxy-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
• 作为产物：
  描述：

  鬼臼毒素 在 氢溴酸 、 四丁基碘化铵 、 三乙胺 、 barium carbonate 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 56.25h， 生成 (5S,5aS,8aR,9R)-5-[(4-氟苯基)氨基]-9-(4-羟基-3,5-二甲氧基-苯基)-5a,6,8a,9-四氢-5H-异苯并呋喃并[5,6-f][1,3]苯并二氧戊环-8-酮
  参考文献：
  名称：

  4β-苯胺基-4'-去甲基表鬼臼毒素的有效方法：NPF和W-68的合成

  摘要：

  通过在4-溴表鬼臼毒素的置换反应中使用Bu 4 N + T，获得了具有明显立体选择性和提高产量的4β取代鬼臼毒素同类物。通过这种方法可以高收率制备DNA拓扑异构酶II抑制剂NPF和W-68。

  DOI：

  10.1016/0040-4039(96)00546-1

文献信息

• Antitumor agents. 111. New 4-hydroxylated and 4-halogenated anilino derivatives of 4'-demethylepipodophyllotoxin as potent inhibitors of human DNA topoisomerase II
  作者：Kuo Hsiung Lee、Scott A. Beers、Masami Mori、Zhe Qing Wang、Yao Haur Kuo、Li Li、Su Ying Liu、Jang Yang Chang、Fu Sheng Han、Yung Chi Cheng

  DOI：10.1021/jm00167a013

  日期：1990.5

  A series of C-4 hydroxylated and halogenated anilino derivatives of epipodophyllotoxin or 4'-demethylepipodophyllotoxin have been synthesized and evaluated for their inhibitory activity against the human DNA topoisomerase II as well as for their activity in causing cellular protein-linked DNA breakage. Compounds 11-17 and 22 are more potent than etoposide in causing DNA breakage, while compounds 11-13, 15, 16, and 20 are as active or more active than etoposide in their inhibition of the human DNA topoisomerase II. The cytotoxicity in KB cells appears to have no direct correlation with their ability to inhibit DNA topoisomerase II and to cause protein-linked DNA breaks in cells.
• A one-pot, efficient synthesis of the potent cytotoxic podophyllotoxin derivative NPF
  作者：Laurent Daley、Philippe Meresse、Emmanuel Bertounesque、Claude Monneret

  DOI：10.1016/s0040-4039(97)00450-4

  日期：1997.4

  One-per syntheses of 4'-demethylepipodophyllotoxin 7 and NPF 2 (4'-O-demethyl-4 beta-(4''-fluoroanilino)-4-deoxypodophyllotoxin) are described from podophyllotoxin 3 via a protocol using trimethylsilyl iodide in 72% and 52% overall yields, respectively. (C) 1997 Published by Elsevier Science Ltd.
• A one-pot, efficient and facile synthesis of 4β-arylaminopodophyllotoxins: synthesis of NPF and GL-331 as DNA topoisomerase II inhibitors
  作者：Ahmed Kamal、B.Ashwini Kumar、M. Arifuddin

  DOI：10.1016/j.tetlet.2003.09.110

  日期：2003.11

  A series of 4beta-arylamino-4'-O-demethylepipodophyllotoxins and 4beta-arylaminopodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the BF3 . OEt2/Nal reagent system. Compounds NPF, GL-331 and other DNA topoisomerase 11 inhibitors have been prepared in good to excellent yields by employing this methodology. (C) 2003 Elsevier Ltd. All rights reserved.
• Facile and efficient one-pot synthesis of 4β-arylaminopodophyllotoxins: synthesis of DNA topoisomerase II inhibitors (NPF and W-68)
  作者：Ahmed Kamal、N. Laxman、G. Ramesh

  DOI：10.1016/s0960-894x(00)00407-8

  日期：2000.9

  A series of 4 beta-arylamino-4'-O-demethylepipodophyllotoxins and 4 beta-arylaminoepipodophyllotoxins have been synthesized with significant stereoselectivity and improved yields by employing the methanesulphonic acid/sodium iodide reagent system. Compounds NPF, W-68 and other DNA topoisomerase II inhibitors are prepared in good to excellent yields by this method and these are active or more active than etoposide in their inhibition of the human DNA topoisomerase II. (C) 2000 Elsevier Science Ltd. All rights reserved.
• Zhou; Lee; Cheng, Journal of Medicinal Chemistry, 1994, vol. 37, # 2, p. 287 - 292
  作者：Zhou、Lee、Cheng、Wu、Chen、Guo、Cheng -、Lee

  DOI：——

  日期：——