(2S)-2-[[2-methyl-2-(2-nitrophenyl)propanoyl]amino]-4-phenylmethoxybutanamide | 1056426-48-2

• 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: (2S)-2-[[2-methyl-2-(2-nitrophenyl)propanoyl]amino]-4-phenylmethoxybutanamide
• CAS: 1056426-48-2
• 化学式: C₂₁H₂₅N₃O₅
• 分子量: 399.447
• InChiKey: UHEGDGXSFWEVDO-KRWDZBQOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  127
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-[[2-methyl-2-(2-nitrophenyl)propanoyl]amino]-4-phenylmethoxybutanamide 在 [双(三氟乙酰氧基)碘]苯 作用下， 以 水 、 乙腈 为溶剂， 反应 4.0h， 以91%的产率得到
  参考文献：
  名称：

  N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide as a potential bioreductively activated prodrug of phosphoramide mustard

  摘要：

  N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide isomers (DMNA-NH-CPA,4)were synthesized stereospecifically from Boc-L-Hse(OBn)-OH and the degradation of the corresponding reduced amine 5a was investigated by UV/vis spectroscopy and LC/MS. The rate of cyclization of 5a was found to increase with decreasing pH, with half-lives ranging from 3.2 to 54 min at pH 4 -7.4, suggesting that the cyclization is catalyzed by the hydronium ions. LC/MS analysis of the degradation products of 5a indicates that 4-aminocyclophosphamide is rapidly released from 4 upon reductive activation under acidic conditions and further decomposes into the cytotoxic phosphoramide mustard. These results validated 4-aminocyclophosphamide as a prodrug form of phosphoramide mustard and suggest that compound 4 can potentially be used as a prodrug of phosphoramide mustard for bioreductive activation. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.099
• 作为产物：
  描述：

  (2S)-2-amino-4-phenylmethoxybutanamide 、 2,2-dimethyl-2-(2-nitrophenyl)acetyl chloride 以 二氯甲烷 为溶剂， 反应 5.0h， 生成 (2S)-2-[[2-methyl-2-(2-nitrophenyl)propanoyl]amino]-4-phenylmethoxybutanamide
  参考文献：
  名称：

  N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide as a potential bioreductively activated prodrug of phosphoramide mustard

  摘要：

  N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide isomers (DMNA-NH-CPA,4)were synthesized stereospecifically from Boc-L-Hse(OBn)-OH and the degradation of the corresponding reduced amine 5a was investigated by UV/vis spectroscopy and LC/MS. The rate of cyclization of 5a was found to increase with decreasing pH, with half-lives ranging from 3.2 to 54 min at pH 4 -7.4, suggesting that the cyclization is catalyzed by the hydronium ions. LC/MS analysis of the degradation products of 5a indicates that 4-aminocyclophosphamide is rapidly released from 4 upon reductive activation under acidic conditions and further decomposes into the cytotoxic phosphoramide mustard. These results validated 4-aminocyclophosphamide as a prodrug form of phosphoramide mustard and suggest that compound 4 can potentially be used as a prodrug of phosphoramide mustard for bioreductive activation. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.05.099

文献信息

• N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide as a potential bioreductively activated prodrug of phosphoramide mustard
  作者：Yongying Jiang、Longqin Hu

  DOI：10.1016/j.bmcl.2008.05.099

  日期：2008.7

  N-(2,2-Dimethyl-2-(2-nitrophenyl)acetyl)-4-aminocyclophosphamide isomers (DMNA-NH-CPA,4)were synthesized stereospecifically from Boc-L-Hse(OBn)-OH and the degradation of the corresponding reduced amine 5a was investigated by UV/vis spectroscopy and LC/MS. The rate of cyclization of 5a was found to increase with decreasing pH, with half-lives ranging from 3.2 to 54 min at pH 4 -7.4, suggesting that the cyclization is catalyzed by the hydronium ions. LC/MS analysis of the degradation products of 5a indicates that 4-aminocyclophosphamide is rapidly released from 4 upon reductive activation under acidic conditions and further decomposes into the cytotoxic phosphoramide mustard. These results validated 4-aminocyclophosphamide as a prodrug form of phosphoramide mustard and suggest that compound 4 can potentially be used as a prodrug of phosphoramide mustard for bioreductive activation. (c) 2008 Elsevier Ltd. All rights reserved.