11-aminooxy-4,9-bis(tert-butoxycarbonyl)-4,9-diaza-1-(tert-butoxycarbonyl)aminoundecane | 910482-72-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 11-aminooxy-4,9-bis(tert-butoxycarbonyl)-4,9-diaza-1-(tert-butoxycarbonyl)aminoundecane
• 英文别名: {4-[(2-aminooxyethyl)-4-tert-butoxycarbonylamino]butyl}-(3-tert-butoxycarbonylaminopropyl)carbamic acid tert-butyl ester；tert-butyl N-(2-aminooxyethyl)-N-[4-[(2-methylpropan-2-yl)oxycarbonyl-[3-[(2-methylpropan-2-yl)oxycarbonylamino]propyl]amino]butyl]carbamate
• CAS: 910482-72-3
• 化学式: C₂₄H₄₈N₄O₇
• 分子量: 504.668
• InChiKey: PAPGXCVDHDBHRE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  35
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  133
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  11-aminooxy-4,9-bis(tert-butoxycarbonyl)-4,9-diaza-1-(tert-butoxycarbonyl)aminoundecane 、 (S)-11-formy-4-乙基-4-羟基-1,12-二氢-4H-2-噁-6,12a-二氮杂-二苯并b,h芴-3,13-二酮 以 乙醇 为溶剂， 反应 8.0h， 以70%的产率得到[3-({4-[(2-(7-(camptothecinyl-7-methylidene)aminooxyethyl)-tert-butoxycarbonyl)amino]butyl}-tert-butoxycarbonylamino)propyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  Synthesis and Cytotoxic Activity of Polyamine Analogues of Camptothecin

  摘要：

  A number of derivatives of camptothecin with a polyamine chain linked to position 7 of camptothecin via an amino, imino, or oxyiminomethyl group were synthesized and tested for their biological activity. All compounds showed marked growth inhibitory activity against the H460 human lung carcinoma cell line. In particular, the iminomethyl derivatives where the amino groups of the chain were protected with Boc groups exhibited a high potency, with IC50 values of similar to 10(-8) M. The pattern of DNA cleavage in vitro and the persistence of the cleavable ternary complex drug-DNA-topoisomerase I observed with polyamine conjugates containing free amino groups support a contribution of specific drug interaction with DNA as a determinant of activity. Modeling of compound 7c in the complex with topoisomerase 1 and DNA is consistent with this hypothesis. The lack of a specific correlation between stabilization of the cleavable complex and growth inhibition likely reflects multiple factors including the cellular pharmacokinetic behavior related to the variable lipophilicity of the conjugate, and the nature and linkage of the polyamine moiety.

  DOI：

  10.1021/jm060285b
• 作为产物：
  描述：

  (3-tert-butoxycarbonylaminopropyl)-(4-{tert-butoxycarbonyl-[2-(1,3-dioxo-1,3-dihydroisoindol-2-yloxy)ethyl]amino}butyl)carbamic acid tert-butyl ester 在 肼 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以65%的产率得到11-aminooxy-4,9-bis(tert-butoxycarbonyl)-4,9-diaza-1-(tert-butoxycarbonyl)aminoundecane
  参考文献：
  名称：

  Synthesis and Cytotoxic Activity of Polyamine Analogues of Camptothecin

  摘要：

  A number of derivatives of camptothecin with a polyamine chain linked to position 7 of camptothecin via an amino, imino, or oxyiminomethyl group were synthesized and tested for their biological activity. All compounds showed marked growth inhibitory activity against the H460 human lung carcinoma cell line. In particular, the iminomethyl derivatives where the amino groups of the chain were protected with Boc groups exhibited a high potency, with IC50 values of similar to 10(-8) M. The pattern of DNA cleavage in vitro and the persistence of the cleavable ternary complex drug-DNA-topoisomerase I observed with polyamine conjugates containing free amino groups support a contribution of specific drug interaction with DNA as a determinant of activity. Modeling of compound 7c in the complex with topoisomerase 1 and DNA is consistent with this hypothesis. The lack of a specific correlation between stabilization of the cleavable complex and growth inhibition likely reflects multiple factors including the cellular pharmacokinetic behavior related to the variable lipophilicity of the conjugate, and the nature and linkage of the polyamine moiety.

  DOI：

  10.1021/jm060285b

文献信息

• Aminooxy analogues of spermine and their monoacetyl derivatives
  作者：A. R. Simonyan、J. Vepsalainen、A. R. Khomutov

  DOI：10.1134/s1068162006060112

  日期：2006.12

  Convenient methods of synthesis of 1-aminooxy-3,8-diaza-11-aminoundecane, its earlier unknown N1-and N11-acetyl derivatives, and also 1,10-bis(aminooxy)-3,8-diazadecane are suggested. It is shown that it is possible to selectively delete the acid-labile ethoxyethylidene protection of aminooxy group by hydrosulfates in the presence of N-tert-butyloxycarbonyl group.

  建议了合成 1-氨基氧基-3,8-二氮杂-11-氨基十一烷、其早期未知的 N1-和 N11-乙酰衍生物以及 1,10-双(氨基氧基)-3,8-二氮杂癸烷的便捷方法。结果表明，在 N-叔丁氧基羰基存在下，可以通过硫酸氢盐选择性地消除氨氧基的酸不稳定乙氧基亚乙基保护。
• Synthesis and Cytotoxic Activity of Polyamine Analogues of Camptothecin
  作者：Sabrina Dallavalle、Giuseppe Giannini、Domenico Alloatti、Andrea Casati、Elena Marastoni、Loana Musso、Lucio Merlini、Gabriella Morini、Sergio Penco、Claudio Pisano、Stella Tinelli、Michelandrea De Cesare、Giovanni Luca Beretta、Franco Zunino

  DOI：10.1021/jm060285b

  日期：2006.8.1

  A number of derivatives of camptothecin with a polyamine chain linked to position 7 of camptothecin via an amino, imino, or oxyiminomethyl group were synthesized and tested for their biological activity. All compounds showed marked growth inhibitory activity against the H460 human lung carcinoma cell line. In particular, the iminomethyl derivatives where the amino groups of the chain were protected with Boc groups exhibited a high potency, with IC50 values of similar to 10(-8) M. The pattern of DNA cleavage in vitro and the persistence of the cleavable ternary complex drug-DNA-topoisomerase I observed with polyamine conjugates containing free amino groups support a contribution of specific drug interaction with DNA as a determinant of activity. Modeling of compound 7c in the complex with topoisomerase 1 and DNA is consistent with this hypothesis. The lack of a specific correlation between stabilization of the cleavable complex and growth inhibition likely reflects multiple factors including the cellular pharmacokinetic behavior related to the variable lipophilicity of the conjugate, and the nature and linkage of the polyamine moiety.