4β-amino-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin | 692755-45-6

• 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
• 英文名称: 4β-amino-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin
• 英文别名: (5R,5aR,8aS,9S)-9-amino-5-(4-{[tert-butyl(dimethyl)silyl]oxy}-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(5aH)-one；(5S,5aS,8aR,9R)-5-amino-9-[4-[tert-butyl(dimethyl)silyl]oxy-3,5-dimethoxyphenyl]-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-8-one
• CAS: 692755-45-6
• 化学式: C₂₇H₃₅NO₇Si
• 分子量: 513.663
• InChiKey: JVEXHNVAGYKXPO-QQJYNPJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.75
• 重原子数：
  36
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  98.5
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4β-amino-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 4-β-(butyloxycarbonyl)amino-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin
  参考文献：
  名称：

  Novel carbamate derivatives of 4-β-amino-4′-O-demethyl-4-desoxypodophyllotoxin as inhibitors of topoisomerase II: synthesis and biological evaluation

  摘要：

  合成了一系列新型的4-β-氨基-4′-去甲基-4-去氧蓖麻毒素的氨基甲酸酯衍生物。评估了它们对人DNA拓扑异构酶II的影响及抗增殖活性。化合物4a–c、4g、4j和4k是拓扑异构酶II毒药，能够诱导DNA双链断裂，并且相比于依托泊苷表现出更高的细胞毒性。

  DOI：

  10.1039/b416862c
• 作为产物：
  描述：

  (5R,5aR,8aS,9S)-9-amino-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 4β-amino-4'-tert-butyldimethylsilyloxy-4'-O-demethyl-4-desoxypodophyllotoxin
  参考文献：
  名称：

  9-Amino-podophyllotoxin derivatives, method for the production thereof and pharmaceutical compositions containing said derivatives

  摘要：

  该发明涉及式(I)的化合物，其中R1是从氢、烷基、芳基、芳基烷基、杂芳基、杂芳基烷基、烷基羰基、芳基羰基、芳基烷基羰基、烷氧羰基、芳氧羰基、芳基烷氧羰基、杂环烷氧羰基、烷基磺酰基、芳基磺酰基、芳基烷基磺酰基、膦酸和Si(Ra)2Rb中选择的基团，Y是从HN—NH和N—R2中选择的基团，R3是氢原子、烷基、环烷基、芳基、芳基烷基基团，R4是氢原子或烷基基团，对映体、非对映异构体及其盐。

  公开号：

  US20060247246A1

文献信息

• 9-Amino-podophyllotoxin derivatives, method for the production thereof and pharmaceutical compositions containing said derivatives
  申请人：Monneret Claude

  公开号：US20060247246A1

  公开（公告）日：2006-11-02

  The invention relates to compounds of formula (I), wherein R 1 is a group selected from hydrogen, alkyl, aryl, aryalkil, heteroaryl, heteroarylalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, heterocycloalkoxycarbonyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, phosphonic and Si(Ra) 2 R b , Y is a group selected from HN—NH and N—R 2 , R 3 is a hydrogen atom, an alkyl, cycloalkyl, aryl, arylalkyl group, R 4 is hydrogen atom or an alkyl group, enantiomers, diastereoisomers and the salts thereof.

  该发明涉及式(I)的化合物，其中R1是从氢、烷基、芳基、芳基烷基、杂芳基、杂芳基烷基、烷基羰基、芳基羰基、芳基烷基羰基、烷氧羰基、芳氧羰基、芳基烷氧羰基、杂环烷氧羰基、烷基磺酰基、芳基磺酰基、芳基烷基磺酰基、膦酸和Si(Ra)2Rb中选择的基团，Y是从HN—NH和N—R2中选择的基团，R3是氢原子、烷基、环烷基、芳基、芳基烷基基团，R4是氢原子或烷基基团，对映体、非对映异构体及其盐。
• 9-amino-podophyllotoxin derivatives, method for the production thereof and pharmaceutical compositions containing said derivatives
  申请人：Les Laboratoires Servier

  公开号：US07378419B2

  公开（公告）日：2008-05-27

  The invention relates to compounds of formula (I), wherein R1 is a group selected from hydrogen, alkyl, aryl, aryalkil, heteroaryl, heteroarylalkyl, alkylcarbonyl, arylcarbonyl, arylalkylcarbonyl, alkoxycarbonyl, aryloxycarbonyl, arylalkoxycarbonyl, heterocycloalkoxycarbonyl, alkylsulfonyl, arylsulfonyl, arylalkylsulfonyl, phosphonic and Si(Ra)2Rb, Y is a group selected from HN—NH and N—R2, R3 is a hydrogen atom, an alkyl, cycloalkyl, aryl, arylalkyl group, R4 is hydrogen atom or an alkyl group, enantiomers, diastereoisomers and the salts thereof

  本发明涉及公式（I）的化合物，其中R1是从氢，烷基，芳基，芳基烷基，杂芳基，杂芳基烷基，烷基羰基，芳基羰基，芳基烷基羰基，烷氧羰基，芳氧羰基，芳基烷氧羰基，杂环烷氧羰基，烷基磺酰基，芳基磺酰基，芳基烷基磺酰基，膦酸和Si（Ra）2Rb中选择的基团，Y是选择自HN-NH和N-R2的基团，R3是氢原子，烷基，环烷基，芳基，芳基烷基，R4是氢原子或烷基，其对映异构体，非对映异构体及其盐。
• Novel carbamate derivatives of 4-β-amino-4′-O-demethyl-4-desoxypodophyllotoxin as inhibitors of topoisomerase II: synthesis and biological evaluation
  作者：Maria Duca、Paola B. Arimondo、Stéphane Léonce、Alain Pierré、Bruno Pfeiffer、Claude Monneret、Daniel Dauzonne

  DOI：10.1039/b416862c

  日期：——

  A novel series of carbamate derivatives of 4-β-amino-4′-O-demethyl-4-desoxypodophyllotoxin were synthesized. Their effect on human DNA topoisomerase II and antiproliferative activity was evaluated. Compounds 4a–c, 4g, 4j and 4k are topoisomerase II poisons that induce double-stranded breaks in DNA and exhibit increased cytotoxicity compared to etoposide.

  合成了一系列新型的4-β-氨基-4′-去甲基-4-去氧蓖麻毒素的氨基甲酸酯衍生物。评估了它们对人DNA拓扑异构酶II的影响及抗增殖活性。化合物4a–c、4g、4j和4k是拓扑异构酶II毒药，能够诱导DNA双链断裂，并且相比于依托泊苷表现出更高的细胞毒性。
• Synthesis and Biological Activity of Sulfonamide Derivatives of Epipodophyllotoxin
  作者：Dominique Guianvarc'h、Maria Duca、Chawki Boukarim、Laurence Kraus-Berthier、Stéphane Léonce、Alain Pierré、Bruno Pfeiffer、Pierre Renard、Paola B. Arimondo、Claude Monneret、Daniel Dauzonne

  DOI：10.1021/jm031117b

  日期：2004.4.1

  A series of novel 4beta-substituted sulfonamide derivatives of 4'-O-demethyl-4-desoxypodophyllotoxin has been synthesized. Their effects on human DNA topoisomerase II and, in some cases, on tubulin polymerization were evaluated. Compounds 8a, 8c, 8f, 8g, 8n, 8q, 8r, and 8s and the synthetic precursor 4 are potent topoisomerase II poisons that induce double-stranded breaks in DNA, with either improved or similar activity compared to etoposide. Only the amino precursor, compound 5, was slightly active in tubulin polymerization inhibition assays. We observed that the derivatives bearing an aromatic ring on the 4beta-sulfonamide substituent were either less cytotoxic or equivalent to the parent drug, while the sulfonamides containing an aliphatic side chain and the amino-sulfonamide derivatives, except 8d and 8g, exhibited increased cytoxicity compared to etoposide. In vivo, against the P388 leukemia and the A-549 orthotopic model of lung carcinoma, the most promising compounds were the morpholino- and the piperazino-containing sulfonamides derivatives 8r and 8s.