N-(3-amino-3-imino-propyl)-4-[[4-[[4-[[isopropoxy-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]phosphoryl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide | 1190064-45-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: N-(3-amino-3-imino-propyl)-4-[[4-[[4-[[isopropoxy-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]phosphoryl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide
• 英文别名: N-(3-amino-3-iminopropyl)-1-methyl-4-[[1-methyl-4-[[1-methyl-4-[[[(2S,5R)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy-propan-2-yloxyphosphoryl]amino]pyrrole-2-carbonyl]amino]pyrrole-2-carbonyl]amino]pyrrole-2-carboxamide
• CAS: 1190064-45-9
• 化学式: C₃₄H₄₄N₁₁O₉P
• 分子量: 781.765
• InChiKey: RGRKUFDHKDAQDS-CHOYTINNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  55
• 可旋转键数：
  16
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  258
• 氢给体数：
  7
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  N-(3-amino-3-imino-propyl)-4-[[4-[[4-[[isopropoxy-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]phosphoryl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide 在 carboxypeptidase A 作用下， 以 氘代二甲亚砜 为溶剂， 生成
  参考文献：
  名称：

  Design and synthesis of novel distamycin-modified nucleoside analogues as HIV-1 reverse transcriptase inhibitors

  摘要：

  Design and synthesis of nucleoside analogues have persistently attracted extensive interest because of their potential application in the field of antiviral therapy, and its study also receives additional impetus for improvement in the ProTide technology. Previous studies have made great strides in the design and discovery of monophosphorylated nucleoside analogues as potential kinase-independent antiretrovirals. In this work, a series of nucleoside phosphoramidates modified by distamycin analogues was synthesized and evaluated as nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-1-infected MT-4 and CEM cells, including variations in nucleoside, alkyl moiety, and the structure of distamycin analogues. These compounds exhibited modest potency with the EC50 value in the range of 1.3- to 6.5-fold lower than their corresponding parent drugs in MT-4 cells, which may be attributed to increasing intracellular availability due to the existence of distamycin analogue with favorable hydrophilic-lipophilic equilibrium. Meanwhile, the length of distamycin analogue was considered and assessed as an important factor that could affect antiviral activity and cytotoxicity. Enzymatic and metabolic stability studies have been performed in order to better understand the antiviral behavior of these compounds. The present work revealed the compounds to have a favorable and selective anti-HIV-1 activity in MT-4 and CEM cells, and helped to develop strategies for design and synthesis of effective monophosphorylated nucleoside analogues, which may be applied to antiretroviral research as NRTIs. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2013.12.002
• 作为产物：
  描述：

  O-isopropyl-O'-(2',3'-didehydro-2',3'-dideoxythymidin-5'-yl) phosphonate 在 盐酸 、 四氯化碳 、 乙醇 、 氨 、 三乙胺 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 N-(3-amino-3-imino-propyl)-4-[[4-[[4-[[isopropoxy-[[(2S,5R)-5-(5-methyl-2,4-dioxo-pyrimidin-1-yl)-2,5-dihydrofuran-2-yl]methoxy]phosphoryl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carbonyl]amino]-1-methyl-pyrrole-2-carboxamide
  参考文献：
  名称：

  Design and synthesis of novel distamycin-modified nucleoside analogues as HIV-1 reverse transcriptase inhibitors

  摘要：

  Design and synthesis of nucleoside analogues have persistently attracted extensive interest because of their potential application in the field of antiviral therapy, and its study also receives additional impetus for improvement in the ProTide technology. Previous studies have made great strides in the design and discovery of monophosphorylated nucleoside analogues as potential kinase-independent antiretrovirals. In this work, a series of nucleoside phosphoramidates modified by distamycin analogues was synthesized and evaluated as nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-1-infected MT-4 and CEM cells, including variations in nucleoside, alkyl moiety, and the structure of distamycin analogues. These compounds exhibited modest potency with the EC50 value in the range of 1.3- to 6.5-fold lower than their corresponding parent drugs in MT-4 cells, which may be attributed to increasing intracellular availability due to the existence of distamycin analogue with favorable hydrophilic-lipophilic equilibrium. Meanwhile, the length of distamycin analogue was considered and assessed as an important factor that could affect antiviral activity and cytotoxicity. Enzymatic and metabolic stability studies have been performed in order to better understand the antiviral behavior of these compounds. The present work revealed the compounds to have a favorable and selective anti-HIV-1 activity in MT-4 and CEM cells, and helped to develop strategies for design and synthesis of effective monophosphorylated nucleoside analogues, which may be applied to antiretroviral research as NRTIs. (C) 2013 Elsevier B.V. All rights reserved.

  DOI：

  10.1016/j.antiviral.2013.12.002

文献信息

• Design and synthesis of novel distamycin-modified nucleoside analogues as HIV-1 reverse transcriptase inhibitors
  作者：Chao Li、Chunying Ma、Jin Zhang、Ning Qian、Jingjing Ding、Renzhong Qiao、Yufen Zhao

  DOI：10.1016/j.antiviral.2013.12.002

  日期：2014.2

  Design and synthesis of nucleoside analogues have persistently attracted extensive interest because of their potential application in the field of antiviral therapy, and its study also receives additional impetus for improvement in the ProTide technology. Previous studies have made great strides in the design and discovery of monophosphorylated nucleoside analogues as potential kinase-independent antiretrovirals. In this work, a series of nucleoside phosphoramidates modified by distamycin analogues was synthesized and evaluated as nucleoside reverse transcriptase inhibitors (NRTIs) in HIV-1-infected MT-4 and CEM cells, including variations in nucleoside, alkyl moiety, and the structure of distamycin analogues. These compounds exhibited modest potency with the EC50 value in the range of 1.3- to 6.5-fold lower than their corresponding parent drugs in MT-4 cells, which may be attributed to increasing intracellular availability due to the existence of distamycin analogue with favorable hydrophilic-lipophilic equilibrium. Meanwhile, the length of distamycin analogue was considered and assessed as an important factor that could affect antiviral activity and cytotoxicity. Enzymatic and metabolic stability studies have been performed in order to better understand the antiviral behavior of these compounds. The present work revealed the compounds to have a favorable and selective anti-HIV-1 activity in MT-4 and CEM cells, and helped to develop strategies for design and synthesis of effective monophosphorylated nucleoside analogues, which may be applied to antiretroviral research as NRTIs. (C) 2013 Elsevier B.V. All rights reserved.