4-N-(2-aminopyridine)-4-deoxidation-4'-demethylepipodophyllotoxin | 127882-75-1

• 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: 4-N-(2-aminopyridine)-4-deoxidation-4'-demethylepipodophyllotoxin
• 英文别名: (5S,5aS,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-5-(pyridin-2-ylamino)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 127882-75-1
• 化学式: C₂₆H₂₄N₂O₇
• 分子量: 476.486
• InChiKey: ASQNQDFENBDDNX-CPUMGYLUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  5
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  108
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  4'-O-demethyl-4β-bromo-4-desoxypodophyllotoxin 生成 4-N-(2-aminopyridine)-4-deoxidation-4'-demethylepipodophyllotoxin
  参考文献：
  名称：

  WANG, ZHE-QING;KUO, YAO-HAUR;SCHNUR, DORA;BOWEN, J. PHILLIP;LIU, SU-YING;+, J. MED. CHEM., 33,(1990) N, C. 2660-2666

  摘要：

  DOI：

文献信息

• SAR analysis and biological studies of synthesized podophyllum derivates obtained by N linkage modification at C-4 position
  作者：Huai Wang、Lijun Tang、Yajie Tang、Zhanpeng Yuan

  DOI：10.1016/j.bmc.2014.08.025

  日期：2014.11

  A series of C4-N-substituted podophyllum derivatives were synthesized and tested for cytotoxicity in HeLa, BGC-823, A549, Huh7 and MCF-7 cells by MTT assay. Pharmacologically, most derivatives displayed potent cytotoxicity against at least one of the tested tumor cell lines. Structure activity relationship (SAR) analysis suggests that compounds with imidogen exposed on the pyridine, rather than pyrimidine

  合成了一系列C4-N-取代的鬼臼衍生物，并通过MTT法测试了其在HeLa，BGC-823，A549，Huh7和MCF-7细胞中的细胞毒性。在药理上，大多数衍生物对至少一种测试的肿瘤细胞系表现出强的细胞毒性。结构活性关系（SAR）分析表明，在吡啶（而不是嘧啶）上有亚氨基的化合物表现出显着提高的效价。此外，杂环中氯原子的存在增强了细胞毒性，其顺序为3位＞ 4位＞ 5位＞ 6位。具体来说，两种化合物3g和3h与其他合成的衍生物或参考化合物PPT，DMEP和依托泊苷相比，用鬼臼毒素（PPT）和4'-O-去甲基表鬼臼毒素（DMEP）取代了2-氨基-3-氯吡啶（VP-16）。已显示化合物3g抑制微管聚合，化合物3h影响拓扑异构酶II的催化活性。据称，这两种化合物均导致G 2 / M期停滞和凋亡，其机制是通过增加P53的表达，然后是Bax上调，Bcl-2下调和caspase-3激活。这项工作的结果是，我们得出结论，化合物3g和3h
• Antitumor agents. 113. New 4.beta.-arylamino derivatives of 4'-O-demethylepipodophyllotoxin and related compounds as potent inhibitors of human DNA topoisomerase II
  作者：Zhe Qing Wang、Yao Haur Kuo、Dora Schnur、J. Phillip Bowen、Su Ying Liu、Fu Sheng Han、Jang Yang Chang、Yung Chi Cheng、Kuo Hsiung Lee

  DOI：10.1021/jm00171a050

  日期：1990.9

  A number of 4'-O-demethylepipodophyllotoxin derivatives possessing various 4 beta-N-, 4 beta-O- or 4 beta-S-aromatic rings 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. The results indicated, that for DNA topoisomerase II, a basic unsubstituted 4 beta-anilino moiety is structurally required for the enhanced activity. Substitution on this moiety with CN, COOCH3, COOC2H5, OH and COOCH3, OCH3, COCH3, CH2OH, OCH2O, OCH2CH2O, phenoxy, morpholino, NO2, and NH2 either at the para and/or the meta position yielded compounds which are as potent or more potent than etoposide. Substitution with COOC2H5 and OH at the ortho position afforded inactive compounds. Replacement of the aryl nitrogen with oxygen or sulfur gave compounds which are much less active or inactive. However, replacement of the phenyl ring with a pyridine nucleus furnished compounds which are as active or slightly more active than etoposide. There is a lack of correlation between the ability of these compounds in inhibiting DNA topoisomerase II and in causing protein-linked DNA breaks.