4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate | 1340543-31-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate
• 英文别名: (4-nitrophenyl)methyl N-(6-phenylmethoxy-7H-purin-2-yl)carbamate
• CAS: 1340543-31-8
• 化学式: C₂₀H₁₆N₆O₅
• 分子量: 420.384
• InChiKey: DQKSHGBGZOPHGE-UHFFFAOYSA-N

物化性质

• 密度：
  1.510±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate 在 乙二胺四乙酸 、 锌 作用下， 反应 0.07h， 生成 O-6-苄基鸟嘌呤
  参考文献：
  名称：

  4-Nitrobenzyloxycarbonyl Derivatives of O⁶-Benzylguanine as Hypoxia-Activated Prodrug Inhibitors of O⁶-Alkylguanine-DNA Alkyltransferase (AGT), Which Produces Resistance to Agents Targeting the O-6 Position of DNA Guanine

  摘要：

  A series of 4-nitrobenzyloxycarbonyl prodrug derivatives of O-6-benzylguanine (O-6-BG), conceived as pro-drugs of O-6-BG, an inhibitor of the resistance protein O-6-alkylguanine-DNA alkyltransferase (ACT), were synthesized and evaluated for their ability to undergo bioreductive activation by reductase enzymes under oxygen deficiency. Three agents of this class, 4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate (1) and its monomethyl (2) and gem-dimethyl analogues (3), were tested for activation by reductase enzyme systems under oxygen deficient conditions. Compound 3, the most water-soluble of these agents, gave the highest yield of O-6-BG following reduction of the nitro group trigger. Compound 3 was also evaluated for its ability to sensitize 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (laromustine)-resistant DU145 human prostate carcinoma cells, which express high levels of AGT, to the cytotoxic effects of this agent under normoxic and oxygen deficient conditions. While 3 had little or no effect on laromustine cytotoxicity under aerobic conditions, significant enhancement occurred under oxygen deficiency, providing evidence for the preferential release of the AGT inhibitor O-6-BG under hypoxia.

  DOI：

  10.1021/jm201115f
• 作为产物：
  描述：

  (6-(benzyloxy)-2-((((4-nitrobenzyl)oxy)carbonyl)amino)-9H-purin-9-yl)methyl pivalate 在 氨 作用下， 以 甲醇 为溶剂， 反应 40.0h， 以85%的产率得到4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate
  参考文献：
  名称：

  4-Nitrobenzyloxycarbonyl Derivatives of O⁶-Benzylguanine as Hypoxia-Activated Prodrug Inhibitors of O⁶-Alkylguanine-DNA Alkyltransferase (AGT), Which Produces Resistance to Agents Targeting the O-6 Position of DNA Guanine

  摘要：

  A series of 4-nitrobenzyloxycarbonyl prodrug derivatives of O-6-benzylguanine (O-6-BG), conceived as pro-drugs of O-6-BG, an inhibitor of the resistance protein O-6-alkylguanine-DNA alkyltransferase (ACT), were synthesized and evaluated for their ability to undergo bioreductive activation by reductase enzymes under oxygen deficiency. Three agents of this class, 4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate (1) and its monomethyl (2) and gem-dimethyl analogues (3), were tested for activation by reductase enzyme systems under oxygen deficient conditions. Compound 3, the most water-soluble of these agents, gave the highest yield of O-6-BG following reduction of the nitro group trigger. Compound 3 was also evaluated for its ability to sensitize 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (laromustine)-resistant DU145 human prostate carcinoma cells, which express high levels of AGT, to the cytotoxic effects of this agent under normoxic and oxygen deficient conditions. While 3 had little or no effect on laromustine cytotoxicity under aerobic conditions, significant enhancement occurred under oxygen deficiency, providing evidence for the preferential release of the AGT inhibitor O-6-BG under hypoxia.

  DOI：

  10.1021/jm201115f

文献信息

• 4-Nitrobenzyloxycarbonyl Derivatives of <i>O</i>⁶-Benzylguanine as Hypoxia-Activated Prodrug Inhibitors of <i>O</i>⁶-Alkylguanine-DNA Alkyltransferase (AGT), Which Produces Resistance to Agents Targeting the <i>O</i>-6 Position of DNA Guanine
  作者：Rui Zhu、Mao-Chin Liu、Mei-Zhen Luo、Philip G. Penketh、Raymond P. Baumann、Krishnamurthy Shyam、Alan C. Sartorelli

  DOI：10.1021/jm201115f

  日期：2011.11.10

  A series of 4-nitrobenzyloxycarbonyl prodrug derivatives of O-6-benzylguanine (O-6-BG), conceived as pro-drugs of O-6-BG, an inhibitor of the resistance protein O-6-alkylguanine-DNA alkyltransferase (ACT), were synthesized and evaluated for their ability to undergo bioreductive activation by reductase enzymes under oxygen deficiency. Three agents of this class, 4-nitrobenzyl (6-(benzyloxy)-9H-purin-2-yl)carbamate (1) and its monomethyl (2) and gem-dimethyl analogues (3), were tested for activation by reductase enzyme systems under oxygen deficient conditions. Compound 3, the most water-soluble of these agents, gave the highest yield of O-6-BG following reduction of the nitro group trigger. Compound 3 was also evaluated for its ability to sensitize 1,2-bis(methylsulfonyl)-1-(2-chloroethyl)-2-[(methylamino)carbonyl]hydrazine (laromustine)-resistant DU145 human prostate carcinoma cells, which express high levels of AGT, to the cytotoxic effects of this agent under normoxic and oxygen deficient conditions. While 3 had little or no effect on laromustine cytotoxicity under aerobic conditions, significant enhancement occurred under oxygen deficiency, providing evidence for the preferential release of the AGT inhibitor O-6-BG under hypoxia.