N-(cyanomethyl)-N-<(ethoxycarbonyl)methyl>daunorubicin | 103450-91-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 蒽环类药物
• 英文名称: N-(cyanomethyl)-N-<(ethoxycarbonyl)methyl>daunorubicin
• 英文别名: 5,12-Naphthacenedione, 7,8,9,10-tetrahydro-8-acetyl-10-((3-((cyanomethyl)(2-ethoxy-2-oxoethyl)amino)-1-methoxy-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy)-6,8,11-trihydroxy-, (8S-cis)-；ethyl 2-[[(2S,3S,4S,6R)-6-[[(1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]-3-hydroxy-2-methyloxan-4-yl]-(cyanomethyl)amino]acetate
• CAS: 103450-91-5
• 化学式: C₃₃H₃₆N₂O₁₂
• 分子量: 652.655
• InChiKey: KPDKPIRUSCZADV-PLKJNFEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  47
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  213
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  N-(cyanomethyl)-N-<(ethoxycarbonyl)methyl>daunorubicin 在 sodium hydroxide 作用下， 反应 0.5h， 生成 Sodium; {[(2S,3S,4S,6R)-6-((1S,3S)-3-acetyl-3,5,12-trihydroxy-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy)-3-hydroxy-2-methyl-tetrahydro-pyran-4-yl]-cyanomethyl-amino}-acetate
  参考文献：
  名称：

  N-(Cyanomethyl)- and N-(2-methoxy-1-cyanoethyl)anthracyclines and related carboxyl derivatives

  摘要：

  Treatment of doxorubicin with formaldehyde and NaCN afforded the N-(cyanomethyl) derivative as a stable alpha-cyanoamine with but moderate antitumor activity in mice, although it was prototypal to the intensely potent alpha-cyanomorpholine derivative. 2-Methoxyacetaldehyde and NaCN afforded the N-(2-methoxy-1-cyanoethyl) derivative as an open-chain analogue of the cyanomorpholine. This analogue underwent rapid hydrolysis to doxorubicin and appeared to act as a prodrug, giving increased antitumor efficacy although with decreased potency. N-(Carboxymethyl)daunorubicin was a highly water-soluble but inactive analogue, synthesized by N-alkylation with ethyl iodoacetate and saponification. The similar N-alkylation of N-(cyanomethyl) daunorubicin demonstrated the combining of N-alkyl chains having different functional substituents.

  DOI：

  10.1021/jm00160a047
• 作为产物：
  描述：

  N-(cyanomethyl)daunorubicin 、 碘代醋酸乙酯 在 sodium acetate 作用下， 反应 96.0h， 生成 N-(cyanomethyl)-N-<(ethoxycarbonyl)methyl>daunorubicin
  参考文献：
  名称：

  N-(Cyanomethyl)- and N-(2-methoxy-1-cyanoethyl)anthracyclines and related carboxyl derivatives

  摘要：

  Treatment of doxorubicin with formaldehyde and NaCN afforded the N-(cyanomethyl) derivative as a stable alpha-cyanoamine with but moderate antitumor activity in mice, although it was prototypal to the intensely potent alpha-cyanomorpholine derivative. 2-Methoxyacetaldehyde and NaCN afforded the N-(2-methoxy-1-cyanoethyl) derivative as an open-chain analogue of the cyanomorpholine. This analogue underwent rapid hydrolysis to doxorubicin and appeared to act as a prodrug, giving increased antitumor efficacy although with decreased potency. N-(Carboxymethyl)daunorubicin was a highly water-soluble but inactive analogue, synthesized by N-alkylation with ethyl iodoacetate and saponification. The similar N-alkylation of N-(cyanomethyl) daunorubicin demonstrated the combining of N-alkyl chains having different functional substituents.

  DOI：

  10.1021/jm00160a047

文献信息

• N-(Cyanomethyl)- and N-(2-methoxy-1-cyanoethyl)anthracyclines and related carboxyl derivatives
  作者：Edward M. Acton、George L. Tong、Dorris L. Taylor、David G. Streeter、Joyce A. Filppi、Richard L. Wolgemuth

  DOI：10.1021/jm00160a047

  日期：1986.10

  Treatment of doxorubicin with formaldehyde and NaCN afforded the N-(cyanomethyl) derivative as a stable alpha-cyanoamine with but moderate antitumor activity in mice, although it was prototypal to the intensely potent alpha-cyanomorpholine derivative. 2-Methoxyacetaldehyde and NaCN afforded the N-(2-methoxy-1-cyanoethyl) derivative as an open-chain analogue of the cyanomorpholine. This analogue underwent rapid hydrolysis to doxorubicin and appeared to act as a prodrug, giving increased antitumor efficacy although with decreased potency. N-(Carboxymethyl)daunorubicin was a highly water-soluble but inactive analogue, synthesized by N-alkylation with ethyl iodoacetate and saponification. The similar N-alkylation of N-(cyanomethyl) daunorubicin demonstrated the combining of N-alkyl chains having different functional substituents.