N-(7-quinolinyl)-5-O-tert-butyldimethylsilyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol | 1061229-96-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-(7-quinolinyl)-5-O-tert-butyldimethylsilyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol
• CAS: 1061229-96-6
• 化学式: C₂₄H₃₆N₂O₃Si
• 分子量: 428.647
• InChiKey: GAKDMAMYJIJKBP-BHIFYINESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.96
• 重原子数：
  30.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  43.82
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  N-(7-quinolinyl)-5-O-tert-butyldimethylsilyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol 、 三氟乙酸 以 水 为溶剂， 以49%的产率得到1,4-dideoxy-1,4-imino-N-(7-quinolinyl)methyl-D-ribitol trifluoroacetate
  参考文献：
  名称：

  N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase

  摘要：

  A key enzyme within the purine salvage pathway of parasites, nucleoside hydrolase, is proposed as a good target for new antiparasitic drugs. We have developed N-arylmethyl-iminoribitol derivatives as a novel class of inhibitors against a purine specific nucleoside hydrolase from Trypanosoma vivax. Several of our inhibitors exhibited low nanomolar activity, with 1,4-dideoxy-1,4-imino-N-(8-quinolinyl)methyl-D-ribitol (UAMC-00115, K-i 10.8 nM), N-(9-deaza-adenin-9-yl)methyl-1,4-dideoxy-1,4-imino- D-ribitol (K-i 4.1 nM), and N-(9-deazahypoxanthin-9-yl) methyl-1,4-dideoxy-1,4-imino- D-ribitol (K-i 4.4 nM) being the three most active compounds. Docking studies of the most active inhibitors revealed several important interactions with the enzyme. Among these interactions are aromatic stacking of the nucleobase mimic with two Trp-residues, and hydrogen bonds between the hydroxyl groups of the inhibitors and amino acid residues in the active site. During the course of these docking studies we also identified a strong interaction between the Asp40 residue from the enzyme and the inhibitor. This is an interaction which has not previously been considered as being important. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.056
• 作为产物：
  描述：

  7-(溴甲基)喹啉 、 (3AR,4R,6AS)-4-[[[(叔丁酯)二甲基硅烷基]氧基]甲基]四氢-2,2-二甲基-4H-1,3-二氧杂环戊烯并[4,5-C]吡咯 在 potassium hydrogencarbonate 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以0.15 g的产率得到N-(7-quinolinyl)-5-O-tert-butyldimethylsilyl-1,4-dideoxy-1,4-imino-2,3-O-isopropylidene-D-ribitol
  参考文献：
  名称：

  N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase

  摘要：

  A key enzyme within the purine salvage pathway of parasites, nucleoside hydrolase, is proposed as a good target for new antiparasitic drugs. We have developed N-arylmethyl-iminoribitol derivatives as a novel class of inhibitors against a purine specific nucleoside hydrolase from Trypanosoma vivax. Several of our inhibitors exhibited low nanomolar activity, with 1,4-dideoxy-1,4-imino-N-(8-quinolinyl)methyl-D-ribitol (UAMC-00115, K-i 10.8 nM), N-(9-deaza-adenin-9-yl)methyl-1,4-dideoxy-1,4-imino- D-ribitol (K-i 4.1 nM), and N-(9-deazahypoxanthin-9-yl) methyl-1,4-dideoxy-1,4-imino- D-ribitol (K-i 4.4 nM) being the three most active compounds. Docking studies of the most active inhibitors revealed several important interactions with the enzyme. Among these interactions are aromatic stacking of the nucleobase mimic with two Trp-residues, and hydrogen bonds between the hydroxyl groups of the inhibitors and amino acid residues in the active site. During the course of these docking studies we also identified a strong interaction between the Asp40 residue from the enzyme and the inhibitor. This is an interaction which has not previously been considered as being important. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.05.056