N-(((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N,N'-bis(2,4-dimethoxybenzyl)methanedisulfonamide | 943980-77-6

• 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: N-(((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N,N'-bis(2,4-dimethoxybenzyl)methanedisulfonamide
• CAS: 943980-77-6
• 化学式: C₃₂H₄₁N₇O₁₁S₂
• 分子量: 763.85
• InChiKey: WLADOHYAOIPZOS-QWOIFIOOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.77
• 重原子数：
  52.0
• 可旋转键数：
  15.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  217.78
• 氢给体数：
  2.0
• 氢受体数：
  16.0

反应信息

• 作为反应物：
  描述：

  N-(((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N,N'-bis(2,4-dimethoxybenzyl)methanedisulfonamide 在 三乙基硅烷 、 偶氮二甲酸二异丙酯 、 三苯基膦 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 7.0h， 生成
  参考文献：
  名称：

  Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

  摘要：

  A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.035
• 作为产物：
  描述：

  2,4-二甲氧基苯甲胺 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 生成 N-(((3aR,4R,6R,6aR)-6-(6-amino-9H-purin-9-yl)-2,2-dimethyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl)-N,N'-bis(2,4-dimethoxybenzyl)methanedisulfonamide
  参考文献：
  名称：

  Methylenebis(sulfonamide) linked nicotinamide adenine dinucleotide analogue as an inosine monophosphate dehydrogenase inhibitor

  摘要：

  A methylenebis(sulfonamide) linked NAD analogue has been designed to circumvent the metabolically unstable, ionic nature of the natural pyrophosphate linkage. This NAD analogue is assembled through two Mitsunobu reactions of a methylenebis(sulfonamide) linker with two protected nucleosides. A 2,4-dimethoxybenzyl group is used as a sulfonamide protective group, which allows facile removal under mildly acidic conditions. This NAD analogue inhibits IMPDH at low micromolar concentration. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.03.035

文献信息

• Bis(sulfonamide) isosters of mycophenolic adenine dinucleotide analogues: Inhibition of inosine monophosphate dehydrogenase
  作者：Liqiang Chen、Riccardo Petrelli、Magdalena Olesiak、Daniel J. Wilson、Nicholas P. Labello、Krzysztof W. Pankiewicz

  DOI：10.1016/j.bmc.2008.06.003

  日期：2008.8

  Synthesis of novel inhibitors of human IMP dehydrogenase is described. These inhibitors are isosteric methylenebis(sulfonamide) analogues 5-8 of earlier reported mycophenolic adenine methylenebis(phosphonate)s 1-3. The parent bis(phosphonate) 1 and its bis(sulfonamide) analogue 5 showed similar sub-micromolar inhibitory activity against IMPDH2 (K(i) approximately 0.2 microM). However, the bis(sulfonamide)

  描述了人IMP脱氢酶的新型抑制剂的合成。这些抑制剂是较早报道的霉菌酚腺嘌呤亚甲基双（膦酸酯）1-3的等规亚甲基双（磺酰胺）类似物5-8。母体双（膦酸酯）1及其双（磺酰胺）类似物5对IMPDH2具有类似的亚微摩尔抑制活性（K（i）约为0.2 microM）。但是，在腺嘌呤2位被取代的双（磺酰胺）类似物6和8的有效IMPPD2抑制剂（K（i）= 0.3-0.4 microM）比相应的母体双（膦酸酯）低约3至10倍。 s 2和3（K（i）= 0.04-0.11 microM）。