4β-((E)-3-(4-methoxy-3-nitrophenyl)-2-(3,4,5-trimethoxyphenyl)acrylamido)-4-deoxypodophyllotoxin | 1322005-57-1

• 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
• 英文名称: 4β-((E)-3-(4-methoxy-3-nitrophenyl)-2-(3,4,5-trimethoxyphenyl)acrylamido)-4-deoxypodophyllotoxin
• 英文别名: 4β-(E)-3-(4-methoxy-3-nitrophenyl)-2-(3,4,5-trimethoxyphenyl)acrylamidopodophyllotoxin；(E)-N-[(5S,5aS,8aR,9R)-8-oxo-9-(3,4,5-trimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-5-yl]-3-(4-methoxy-3-nitrophenyl)-2-(3,4,5-trimethoxyphenyl)prop-2-enamide
• CAS: 1322005-57-1
• 化学式: C₄₁H₄₀N₂O₁₄
• 分子量: 784.774
• InChiKey: DZZKEKQTCPGPCE-ASUSNCLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  57
• 可旋转键数：
  12
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  184
• 氢给体数：
  1
• 氢受体数：
  14

反应信息

• 作为产物：
  描述：

  4β-amino-4-deoxypodophyllotoxin 、 (E)-3-(3'-nitro-4'-dimethoxyphenyl)-2-(3'',4'',5''-trimethoxyphenyl)acrylic acid 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以97%的产率得到4β-((E)-3-(4-methoxy-3-nitrophenyl)-2-(3,4,5-trimethoxyphenyl)acrylamido)-4-deoxypodophyllotoxin
  参考文献：
  名称：

  SUBSTITUTED 4-BETA-ACRYLAMIDOPODOPHYLLOTOXIN CONGENERS AS ANTITUMOUR ANTIBIOTICS AND THE PROCESS FOR PREPARATION THEREOF

  摘要：

  本发明提供通式（3）的化合物，作为潜在的抗人类癌细胞系的抗肿瘤剂。本发明还提供一种合成通式（3）的4β-丙烯酰胺基淫羊藿毒素同系物的方法，其中R和R1是芳基，R选自3,4,5-三甲氧基苯基或2-甲氧基苯基，R1选自4-羟基-3-甲氧基苯基、3-羟基-4-甲氧基苯基、4-氟-3-甲氧基苯基、3-氟-4-甲氧基苯基、2-氟-5-甲氧基苯基、2-氟-4-甲氧基苯基、4-羟基-3-硝基苯基、4-甲氧基-3-硝基苯基、4-硝基苯基、3-硝基苯基、2-硝基苯基、4-甲氧基苯基、3-甲氧基苯基和4-羟基苯基的群。

  公开号：

  US20130225672A1

文献信息

• [EN] SUBSTITUTED 4-BETA-ACRYLAMIDOPODOPHYLLOTOXIN CONGENERS AS ANTITUMOUR ANTIBIOTICS AND THE PROCESS FOR PREPARATION THEREOF<br/>[FR] CONGÉNÈRES DE 4-BÊTA-ACRYLAMIDOPODOPHYLLOTOXINE SUBSTITUÉS EN TANT QU'ANTIBIOTIQUES ANTITUMORAUX ET LEUR PROCÉDÉ DE PRÉPARATION
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2012063250A1

  公开（公告）日：2012-05-18

  The present invention provides compounds of general formula (3) as useful potential antitumour agents against human cancer cell lines. The present invention further provides a process for the synthesis of 4β-acrylamidopodophyllotoxin congeners of general formula (3). wherein R and R1 are an aryl group and R is selected from 3, 4, 5-trimethoxyphenyl or 2-methoxy phenyl and R1 is selected from the group consisting of 4-hydroxy-3- methoxyphenyl, 3-hydroxy-4-methoxyphenyl, 4-fluoro-3-methoxyphenyl, 3-fluoro-4- methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 4-hydroxy-3- nitrophenyl, 4-methoxy-3-nitrophenyl, 4-nitrophenyl, 3-nitrophenyl, 2-nitro phenyl, 4- methoxyphenyl, 3-methoxyphenyl and 4-hydroxyphenyl.

  本发明提供了一种通式（3）的化合物，作为潜在的抗人类癌细胞系肿瘤药物。本发明还提供了一种合成通式（3）的4β-丙烯酰胺基青叶子碱类似物的方法。其中R和R1是芳基基团，R选自3,4,5-三甲氧基苯基或2-甲氧基苯基，R1选自4-羟基-3-甲氧基苯基、3-羟基-4-甲氧基苯基、4-氟-3-甲氧基苯基、3-氟-4-甲氧基苯基、2-氟-5-甲氧基苯基、2-氟-4-甲氧基苯基、4-羟基-3-硝基苯基、4-甲氧基-3-硝基苯基、4-硝基苯基、3-硝基苯基、2-硝基苯基、4-甲氧基苯基、3-甲氧基苯基和4-羟基苯基。
• SUBSTITUTED 4-BETA-ACRYLAMIDOPODOPHYLLOTOXIN CONGENERS AS ANTITUMOUR ANTIBIOTICS AND THE PROCESS FOR PREPARATION THEREOF
  申请人：Ahmed Kamal

  公开号：US20130225672A1

  公开（公告）日：2013-08-29

  The present invention provides compounds of general formula (3) as useful potential antitumour agents against human cancer cell lines. The present invention further provides a process for the synthesis of 4β-acrylamidopodophyllotoxin congeners of general formula (3), wherein R and R1 are an aryl group and R is selected from 3,4,5-trimethoxyphenyl or 2-methoxy phenyl and R1 is selected from the group consisting of 4-hydroxy-3-methoxyphenyl, 3-hydroxy-4-methoxyphenyl, 4-fluoro-3-methoxyphenyl, 3-fluoro-4-methoxyphenyl, 2-fluoro-5-methoxyphenyl, 2-fluoro-4-methoxyphenyl, 4-hydroxy-3-nitrophenyl, 4-methoxy-3-nitrophenyl, 4-nitrophenyl, 3-nitrophenyl, 2-nitro phenyl, 4-methoxyphenyl, 3-methoxyphenyl and 4-hydroxyphenyl.

  本发明提供通式（3）的化合物，作为潜在的抗人类癌细胞系的抗肿瘤剂。本发明还提供一种合成通式（3）的4β-丙烯酰胺基淫羊藿毒素同系物的方法，其中R和R1是芳基，R选自3,4,5-三甲氧基苯基或2-甲氧基苯基，R1选自4-羟基-3-甲氧基苯基、3-羟基-4-甲氧基苯基、4-氟-3-甲氧基苯基、3-氟-4-甲氧基苯基、2-氟-5-甲氧基苯基、2-氟-4-甲氧基苯基、4-羟基-3-硝基苯基、4-甲氧基-3-硝基苯基、4-硝基苯基、3-硝基苯基、2-硝基苯基、4-甲氧基苯基、3-甲氧基苯基和4-羟基苯基的群。
• US8673969B2
  申请人：——

  公开号：US8673969B2

  公开（公告）日：2014-03-18
• Synthesis and biological evaluation of 4β-acrylamidopodophyllotoxin congeners as DNA damaging agents
  作者：Ahmed Kamal、Paidakula Suresh、M. Janaki Ramaiah、Adla Mallareddy、Banala Ashwini Kumar、Paidakula Raju、J. Vinay Gopal、S.N.C.V.L. Pushpavalli、A. Lavanya、Pranjal Sarma、Manika Pal-Bhadra

  DOI：10.1016/j.bmc.2011.06.017

  日期：2011.8

  A series of new 4 beta-acrylamidopodophyllotoxin derivatives (13a-o) were synthesized by coupling of substituted acrylic acids (10a-l and 11m-o) to the 4 beta-aminopodophyllotoxin. The synthesized derivatives 13a-o were evaluated for their cytotoxicity against five human cancer cell lines (breast, oral, colon, lung and ovarian). These podophyllotoxin conjugates have shown promising activity with GI(50) values ranging from <0.1 to 0.29 mu lM. Some of the compounds 13j, 13k and 13l that showed significant antiproliferative activity were also evaluated for related cytotoxic effects in MCF-7 cells, and compared to etoposide. These compounds (13j, 13k and 13l) showed G2/M cell cycle arrest and the apoptotic event was found to be due to both the single-strand DNA breaks as observed by comet assay as well as double-strand breaks as observed by the large accumulation of gamma H2AX foci. (C) 2011 Elsevier Ltd. All rights reserved.