N-(1-cyano-2-methoxyethyl)doxorubicin | 103450-90-4

• 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-(1-cyano-2-methoxyethyl)doxorubicin
• 英文别名: 2-[[(2S,3S,4S,6R)-3-hydroxy-2-methyl-6-[[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-2,4-dihydro-1H-tetracen-1-yl]oxy]oxan-4-yl]amino]-3-methoxypropanenitrile
• CAS: 103450-90-4；103667-16-9；103667-17-0
• 化学式: C₃₁H₃₄N₂O₁₂
• 分子量: 626.617
• InChiKey: GYCDKMVFGHDCQH-FUZOIQPOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.17
• 重原子数：
  45.0
• 可旋转键数：
  9.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  225.1
• 氢给体数：
  6.0
• 氢受体数：
  14.0

反应信息

• 作为反应物：
  描述：

  氰化钠 、 N-(1-cyano-2-methoxyethyl)doxorubicin 以 甲醇 、 氯仿 、 丙酮 为溶剂， 反应 16.0h， 生成 N-(cyanomethyl)doxorubicin 、 {(3aS,4S,6R,7aS)-4-Methyl-6-[(1S,3S)-3,5,12-trihydroxy-3-(2-hydroxy-acetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-1-yloxy]-tetrahydro-pyrano[4,3-d]oxazol-1-yl}-acetonitrile
  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：

  甲氧基乙醛 、 氰化钠 、 盐酸多柔比星 在 盐酸 作用下， 以 水 、 乙腈 为溶剂， 反应 5.0h， 生成 N-(1-cyano-2-methoxyethyl)doxorubicin 、 2-{(2S,4S)-4-[(2R,4S,5S,6S)-4-(1-Cyano-2-methoxy-ethylamino)-5-hydroxy-6-methyl-tetrahydro-pyran-2-yloxy]-2,5,12-trihydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydro-naphthacen-2-yl}-2,3-dihydroxy-propionitrile 、
  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