(2-(3-indolyl)-1(R)-methylcarbamoylethyl)phosphoramidic acid momo(3-deoxy-3-azidothymidyl)ester

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: (2-(3-indolyl)-1(R)-methylcarbamoylethyl)phosphoramidic acid momo(3-deoxy-3-azidothymidyl)ester
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)tetrahydrofuran-2-yl]methoxy-N-[(1R)-1-(1H-indol-3-ylmethyl)-2-(methylamino)-2-oxo-ethyl]phosphonamidic acid；[(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-N-[(2R)-3-(1H-indol-3-yl)-1-(methylamino)-1-oxopropan-2-yl]phosphonamidic acid
• 化学式: C₂₂H₂₇N₈O₇P
• 分子量: 546.48
• InChiKey: RQSHCIBUTXSLNV-WJFTUGDTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  38
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  176
• 氢给体数：
  5
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  甲胺 、 2(R)-(3-deoxy-3-azidothymidyl(hydroxy)phosphorylamino)-3-(3-indolyl)propionic acid methyl ester 以 甲醇 为溶剂， 反应 72.0h， 以99%的产率得到(2-(3-indolyl)-1(R)-methylcarbamoylethyl)phosphoramidic acid momo(3-deoxy-3-azidothymidyl)ester
  参考文献：
  名称：

  Synthesis, in Vitro Anti-Breast Cancer Activity, and Intracellular Decomposition of Amino Acid Methyl Ester and Alkyl Amide Phosphoramidate Monoesters of 3‘-Azido-3‘-deoxythymidine (AZT)

  摘要：

  We report the synthesis and anticancer activity of a series of AZT phosphoramidate monoesters containing amino acid methyl ester (3a-11a) and N-alkyl amide (3b-11b, 9c-9f) moieties. The aromatic amino acid methyl esters were found to be more cytotoxic than the aliphatic analogues toward MCF-7 cells (human pleural effusion breast adenocarcinoma cell line). A marked stereochemical preference for the L-amino acid stereochemistry was also observed in MCF-7 cells. There was no consistent enhancement of cytotoxicity of the methyl amides over the corresponding methyl esters. AZT and the two AZT aromatic amino acid methyl ester phosphoramidates 8a and 9a were found to be more cytotoxic toward MCF-7 cells than to CEM cells (human T-cell lymphoblastic leukemia). The selective cytotoxicity toward MCF-7 cells may be associated with greater intracellular levels of phosphoramidate monoester and/or phosphorylated AZT.

  DOI：

  10.1021/jm000110g

文献信息

• Synthesis, in Vitro Anti-Breast Cancer Activity, and Intracellular Decomposition of Amino Acid Methyl Ester and Alkyl Amide Phosphoramidate Monoesters of 3‘-Azido-3‘-deoxythymidine (AZT)
  作者：Vidhya V. Iyer、George W. Griesgraber、Matthew R. Radmer、Edward J. McIntee、Carston R. Wagner

  DOI：10.1021/jm000110g

  日期：2000.6.1

  We report the synthesis and anticancer activity of a series of AZT phosphoramidate monoesters containing amino acid methyl ester (3a-11a) and N-alkyl amide (3b-11b, 9c-9f) moieties. The aromatic amino acid methyl esters were found to be more cytotoxic than the aliphatic analogues toward MCF-7 cells (human pleural effusion breast adenocarcinoma cell line). A marked stereochemical preference for the L-amino acid stereochemistry was also observed in MCF-7 cells. There was no consistent enhancement of cytotoxicity of the methyl amides over the corresponding methyl esters. AZT and the two AZT aromatic amino acid methyl ester phosphoramidates 8a and 9a were found to be more cytotoxic toward MCF-7 cells than to CEM cells (human T-cell lymphoblastic leukemia). The selective cytotoxicity toward MCF-7 cells may be associated with greater intracellular levels of phosphoramidate monoester and/or phosphorylated AZT.