2-amino-3,5-dihydro-7-[[(2S)-2-(benzyloxycarbonylaminomethyl)-1-pyrrolidinyl]methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one | 913614-57-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-amino-3,5-dihydro-7-[[(2S)-2-(benzyloxycarbonylaminomethyl)-1-pyrrolidinyl]methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one
• 英文别名: benzyl N-[[(2S)-1-[(2-amino-4-oxo-3,5-dihydropyrrolo[3,2-d]pyrimidin-7-yl)methyl]pyrrolidin-2-yl]methyl]carbamate
• CAS: 913614-57-0
• 化学式: C₂₀H₂₄N₆O₃
• 分子量: 396.449
• InChiKey: VOIKGTPPFNXUNE-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  125
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-amino-3,5-dihydro-7-[[(2S)-2-(benzyloxycarbonylaminomethyl)-1-pyrrolidinyl]methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、344.74 kPa 条件下， 反应 6.0h， 以66%的产率得到2-amino-3,5-dihydro-7-[[(2S)-2-(aminomethyl)-1-pyrrolidinyl]methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  Simplified Analogues of Immucillin-G Retain Potent Human Purine Nucleoside Phosphorylase Inhibitory Activity

  摘要：

  A set of deazaguanine derivatives 1-3 targeting human purine nucleoside phosphorylase (hPNP) have been designed and synthesized. The new compounds are characterized by the presence of a structurally simplified "azasugar" motif to be more easily accessible by chemical synthesis than previous inhibitors. In the enzymatic assays, some of the new derivatives proved to be able to inhibit hPNP at low nanomolar concentration, thereby showing the same inhibitory potency in vitro as immucillin-H (IMH). Molecular docking experiments revealed a binding mode to hPNP essentially identical to that of IMH. As a result, the lower in vivo activity exhibited by 1d, compared with that exhibited by IMH, might be ascribed to differences in the pharmacokinetic, rather than pharmacodynamic, profile between these compounds. Derivatives 1a, 1d, and 2c emerged as the most active compounds within this new set and may represent interesting leads in the search for novel hPNP inhibitors.

  DOI：

  10.1021/jm060547+
• 作为产物：
  描述：

  S-叔丁氧羰基-2-(氨基乙基)吡咯烷 在 盐酸 、 sodium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 25.0h， 生成 2-amino-3,5-dihydro-7-[[(2S)-2-(benzyloxycarbonylaminomethyl)-1-pyrrolidinyl]methyl]-4H-pyrrolo[3,2-d]pyrimidin-4-one
  参考文献：
  名称：

  Simplified Analogues of Immucillin-G Retain Potent Human Purine Nucleoside Phosphorylase Inhibitory Activity

  摘要：

  A set of deazaguanine derivatives 1-3 targeting human purine nucleoside phosphorylase (hPNP) have been designed and synthesized. The new compounds are characterized by the presence of a structurally simplified "azasugar" motif to be more easily accessible by chemical synthesis than previous inhibitors. In the enzymatic assays, some of the new derivatives proved to be able to inhibit hPNP at low nanomolar concentration, thereby showing the same inhibitory potency in vitro as immucillin-H (IMH). Molecular docking experiments revealed a binding mode to hPNP essentially identical to that of IMH. As a result, the lower in vivo activity exhibited by 1d, compared with that exhibited by IMH, might be ascribed to differences in the pharmacokinetic, rather than pharmacodynamic, profile between these compounds. Derivatives 1a, 1d, and 2c emerged as the most active compounds within this new set and may represent interesting leads in the search for novel hPNP inhibitors.

  DOI：

  10.1021/jm060547+