(2R,3R,4S)-2-(hydroxymethyl)-1-[(7-methoxy-1H-indol-3-yl)methyl]pyrrolidine-3,4-diol | 1061230-59-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (2R,3R,4S)-2-(hydroxymethyl)-1-[(7-methoxy-1H-indol-3-yl)methyl]pyrrolidine-3,4-diol
• CAS: 1061230-59-8
• 化学式: C₁₅H₂₀N₂O₄
• 分子量: 292.335
• InChiKey: LOKJIIVEEFASRW-TYNCELHUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  89
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (3aR,4R,6aS)-4-(((tert-butyldimethylsilyl)oxy)methyl)-5-((7-methoxy-1H-indol-3-yl)methyl)-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyrrole 在 三氟乙酸 作用下， 以 水 为溶剂， 以0.026 g的产率得到(2R,3R,4S)-2-(hydroxymethyl)-1-[(7-methoxy-1H-indol-3-yl)methyl]pyrrolidine-3,4-diol
  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

文献信息

• N-Arylmethyl substituted iminoribitol derivatives as inhibitors of a purine specific nucleoside hydrolase
  作者：Annelies Goeminne、Maya Berg、Michael McNaughton、Gunther Bal、Georgiana Surpateanu、Pieter Van der Veken、Stijn De Prol、Wim Versées、Jan Steyaert、Achiel Haemers、Koen Augustyns

  DOI：10.1016/j.bmc.2008.05.056

  日期：2008.7

  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.