1-Hydroxy-2,7-diaminomitosen | 102679-61-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-Hydroxy-2,7-diaminomitosen
• 英文别名: 2,7-Diamino-1-hydroxymitosene；(2,6-diamino-3-hydroxy-7-methyl-5,8-dioxo-2,3-dihydro-1H-pyrrolo[1,2-a]indol-4-yl)methyl carbamate
• CAS: 102679-61-8
• 化学式: C₁₄H₁₆N₄O₅
• 分子量: 320.305
• InChiKey: XNHZZRIKMUCTHU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  164
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2'-脱氧鸟苷 、 1-Hydroxy-2,7-diaminomitosen 在 sodium dithionite 、 氧气 作用下， 生成 2,7-Diamino-1-hydroxy-9-{[9-(4-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-ylamino]-methyl}-6-methyl-2,3-dihydro-1H-pyrrolo[1,2-a]indole-5,8-dione
  参考文献：
  名称：

  2,7-二氨基油烯的C-10使DNA烷基化。

  摘要：

  丝裂霉素C和某些类似物将其C-1位置的DNA烷基化，并通过涉及C-10的第二次烷基化使其交联。我们现在表明，对于没有反应性C-1功能的光油类似物，可以发生C-10（氨基甲酸酯基）的单烷基化。在小牛胸腺DNA存在下，连二亚硫酸钠还原2,7-二氨基油烯或2,7-二氨基-1-羟基油烯导致DNA烷基化，分别达到每14和11个碱基一个分子的程度，尽管没有共价结合在催化还原中观察到。在2'-脱氧鸟苷存在下，连二亚硫酸钠还原这些丝裂胺中的每一个，在该核苷酸的2-氨基上单烷基化。2,7-二氨基丝氨酸在体外抑制L-1210白血病细胞集落形成的浓度比丝裂霉素C高3-4倍（效力较弱）。每种油藏也产生DNA单链断裂，但这些损伤与细胞毒性无关，并且不如另一种单官能烷基化剂甲磺酸甲酯产生的断裂突出。线粒体诱导的DNA链断裂可能是由于切除修复内切核酸酶的活性，而不是由醌部分的氧化还原循环产生的氧自由基引起的。没有证据表明2

  DOI：

  10.1021/jm00163a042
• 作为产物：
  描述：

  丝裂霉素 C 在 palladium on activated charcoal 氢气 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 1-Hydroxy-2,7-diaminomitosen
  参考文献：
  名称：

  Nucleotide derivatives of 2,7-diaminomitosene

  摘要：

  Treatment of mitomycin C with pyrimidine nucleotides in acidic media produced derivatives of 2,7-diaminomitosene in which C-1 was covalently bound to the phosphate group of the nucleotides. On reduction, these derivatives liberated the nucleotides and a mitomycin intermediate that alkylated DNA. Their reduction in the presence of 2'-deoxyguanosine produced some bifunctional alkylation as did mitomycin C. They were readily taken up by L1210 leukemia cells, in which they showed potent cytotoxicity. These properties suggest that they are acting as prodrugs capable of conversion into two active species. The uridylate derivative showed activity comparable to that of mitomycin C against P-388 leukemia in mice.

  DOI：

  10.1021/jm00403a016

文献信息

• Aspects of the Chemical Stability of Mitomycin and Porfiromycin in Acidic Solution
  作者：W.J.M. Underberg、H. Lingeman

  DOI：10.1002/jps.2600720518

  日期：1983.5

  Aspects of the degradations of mitomycin and porfiromycin were studied. The initial degradation processes of the compounds in an acidic medium were investigated. Influences of pH, buffers, and other additives such as halogenides and dioctyl sodium sulfosuccinate [sodium 1,4-bis(2-ethylhexyl)sulfosuccinate] were studied. The hydrogen ion catalyzes the degradation of both the uncharged and the protonated

  研究了丝裂霉素和波罗霉素的降解方面。研究了化合物在酸性介质中的初始降解过程。研究了pH，缓冲液和其他添加剂（如卤化物和磺基琥珀酸二辛酯钠[1,4-双（2-乙基己基）磺基琥珀酸钠]的影响。氢离子催化不带电和质子化的物质的降解。阴离子还促进化合物在酸性介质中的降解。可以确定所有催化反应的速率常数。从pH曲线中，校正缓冲液影响后，可以获得氮丙啶氮的准确pKa值。可以解释磺基琥珀酸二辛酯离子的保护作用。
• IYENGAR, BHASHYAM S.;DORR, ROBERT T.;REMERS, WILLIAM A., J. MED. CHEM., 34,(1991) N, C. 1947-1951
  作者：IYENGAR, BHASHYAM S.、DORR, ROBERT T.、REMERS, WILLIAM A.

  DOI：——

  日期：——
• Nucleotide derivatives of 2,7-diaminomitosene
  作者：Bhashyam S. Iyengar、Robert T. Dorr、William A. Remers、Charles D. Kowal

  DOI：10.1021/jm00403a016

  日期：1988.8

  Treatment of mitomycin C with pyrimidine nucleotides in acidic media produced derivatives of 2,7-diaminomitosene in which C-1 was covalently bound to the phosphate group of the nucleotides. On reduction, these derivatives liberated the nucleotides and a mitomycin intermediate that alkylated DNA. Their reduction in the presence of 2'-deoxyguanosine produced some bifunctional alkylation as did mitomycin C. They were readily taken up by L1210 leukemia cells, in which they showed potent cytotoxicity. These properties suggest that they are acting as prodrugs capable of conversion into two active species. The uridylate derivative showed activity comparable to that of mitomycin C against P-388 leukemia in mice.
• Alkylation of DNA by C-10 of 2,7-diaminomitosene
  作者：Bhashyam S. Iyengar、Robert T. Dorr、Nancy G. Shipp、William A. Remers

  DOI：10.1021/jm00163a042

  日期：1990.1

  Mitomycin C and certain analogues alkylate DNA with their C-1 position and cross-link it by a second alkylation involving C-10. We now show that monoalkylation by C-10 (carbamate group) can occur for mitosene analogues that have no reactive C-1 functionality. Sodium dithionite reduction of 2,7-diaminomitosene or 2,7-diamino-1-hydroxymitosene in the presence of calf thymus DNA resulted in alkylation

  丝裂霉素C和某些类似物将其C-1位置的DNA烷基化，并通过涉及C-10的第二次烷基化使其交联。我们现在表明，对于没有反应性C-1功能的光油类似物，可以发生C-10（氨基甲酸酯基）的单烷基化。在小牛胸腺DNA存在下，连二亚硫酸钠还原2,7-二氨基油烯或2,7-二氨基-1-羟基油烯导致DNA烷基化，分别达到每14和11个碱基一个分子的程度，尽管没有共价结合在催化还原中观察到。在2'-脱氧鸟苷存在下，连二亚硫酸钠还原这些丝裂胺中的每一个，在该核苷酸的2-氨基上单烷基化。2,7-二氨基丝氨酸在体外抑制L-1210白血病细胞集落形成的浓度比丝裂霉素C高3-4倍（效力较弱）。每种油藏也产生DNA单链断裂，但这些损伤与细胞毒性无关，并且不如另一种单官能烷基化剂甲磺酸甲酯产生的断裂突出。线粒体诱导的DNA链断裂可能是由于切除修复内切核酸酶的活性，而不是由醌部分的氧化还原循环产生的氧自由基引起的。没有证据表明2