2,6-二氨基-1,5-二氢咪唑并[4,5-c]吡啶-4-酮 | 103438-45-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并吡啶类
• 中文名称: 2,6-二氨基-1,5-二氢咪唑并[4,5-c]吡啶-4-酮
• 英文名称: 2,6-diamino-1,5-dihydro-4H-imidazo<4,5-c>pyridin-4-one
• 英文别名: 2,6-diamino-1,5-dihydro-4H-imidazo[4,5-c]pyridin-4-one；8-Amino-3-deazaguanine；2,6-diamino-1,5-dihydroimidazo[4,5-c]pyridin-4-one
• CAS: 103438-45-5
• 化学式: C₆H₇N₅O
• 分子量: 165.154
• InChiKey: TVGXIIXWKAONRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  12
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  110
• 氢给体数：
  4
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,3-丙酮二羧酸二甲酯 在 氨 、 sodium hydride 、 对甲苯磺酸 、 三氯氧磷 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 243.0h， 生成 2,6-二氨基-1,5-二氢咪唑并[4,5-c]吡啶-4-酮
  参考文献：
  名称：

  Synthesis of 8-amino-3-deazaguanine via imidazole precursors. Antitumor activity and inhibition of purine nucleoside phosphorylase

  摘要：

  8-Amino-3-deazaguanine (15), an analogue of both 3-deazaguanine (1) and 8-aminoguanine (6), an antitumor agent and a purine nucleoside phosphorylase (PNP) inhibitor, respectively, was synthesized from the ammonolysis of an imidazole precursor, methyl 2-(benzoylamino)-5-(cyanomethyl)-1H-imidazole-4-carboxylate (13). The requisite imidazole, methyl 2-(benzoylamino)-4-(methoxycarbonyl)-1H-imidazole-5-acetate (11), was prepared from the monoheterocyclic rearrangement of dimethyl 3-[(5-phenyl-1,2,4-oxadiazol-3-yl)amino]-2-pentenedioate (10) by NaH/DMF. Ammonolysis and subsequent dehydration of 11 provided the penultimate imidazole intermediate 13. Its deprotected (NaOMe/100 degrees C) product, methyl 2-amino-5-(cyanomethyl)-1H-imidazole-4-carboxylate (14), was also converted to 15. 8-Amino-3-deazaguanine, as its methanesulfonic acid (mesylate 7), exhibited an inhibition constant (IC50) of 9.9 microM against isolated mammalian PNP. It was a very weak inhibitor of T and B cell growth and did not enhance 2'-deoxyguanosine toxicity in the same cells. 8-Amino-3-deazaguanine mesylate was not significantly active in L1210 cells in vitro or L1210 leukemic mice. Thus, the amino group introduced in the 8-position of 3-deazaguanine enhances its PNP activity but diminishes its antitumor activity.

  DOI：

  10.1021/jm00160a040

文献信息

• Synthesis of 8-amino-3-deazaguanine via imidazole precursors. Antitumor activity and inhibition of purine nucleoside phosphorylase
  作者：David A. Berry、Richard B. Gilbertsen、P. Dan Cook

  DOI：10.1021/jm00160a040

  日期：1986.10

  8-Amino-3-deazaguanine (15), an analogue of both 3-deazaguanine (1) and 8-aminoguanine (6), an antitumor agent and a purine nucleoside phosphorylase (PNP) inhibitor, respectively, was synthesized from the ammonolysis of an imidazole precursor, methyl 2-(benzoylamino)-5-(cyanomethyl)-1H-imidazole-4-carboxylate (13). The requisite imidazole, methyl 2-(benzoylamino)-4-(methoxycarbonyl)-1H-imidazole-5-acetate (11), was prepared from the monoheterocyclic rearrangement of dimethyl 3-[(5-phenyl-1,2,4-oxadiazol-3-yl)amino]-2-pentenedioate (10) by NaH/DMF. Ammonolysis and subsequent dehydration of 11 provided the penultimate imidazole intermediate 13. Its deprotected (NaOMe/100 degrees C) product, methyl 2-amino-5-(cyanomethyl)-1H-imidazole-4-carboxylate (14), was also converted to 15. 8-Amino-3-deazaguanine, as its methanesulfonic acid (mesylate 7), exhibited an inhibition constant (IC50) of 9.9 microM against isolated mammalian PNP. It was a very weak inhibitor of T and B cell growth and did not enhance 2'-deoxyguanosine toxicity in the same cells. 8-Amino-3-deazaguanine mesylate was not significantly active in L1210 cells in vitro or L1210 leukemic mice. Thus, the amino group introduced in the 8-position of 3-deazaguanine enhances its PNP activity but diminishes its antitumor activity.