5'-O-[N-((R)-2-hydroxy-3,3-dimethylbutanoyl)sulfamoyl]adenosine | 1572039-67-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 5'-O-[N-((R)-2-hydroxy-3,3-dimethylbutanoyl)sulfamoyl]adenosine
• 英文别名: 5'-O-{[(2r)-2-Hydroxy-3,3-Dimethylbutanoyl]sulfamoyl}adenosine；[(2R,3S,4R,5R)-5-(6-aminopurin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl N-[(2R)-2-hydroxy-3,3-dimethylbutanoyl]sulfamate
• CAS: 1572039-67-8
• 化学式: C₁₆H₂₄N₆O₈S
• 分子量: 460.468
• InChiKey: XLQHUZMFAIRQAT-YEFHITBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  220
• 氢给体数：
  5
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  (R)-2,5-dioxopyrrolidin-1-yl-2-(tert-butyldimethylsilyl)oxy-3,3-dimethylbutanoate 在 caesium carbonate 、 三氟乙酸 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 72.0h， 生成 5'-O-[N-((R)-2-hydroxy-3,3-dimethylbutanoyl)sulfamoyl]adenosine
  参考文献：
  名称：

  Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase

  摘要：

  The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with beta-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate. These inhibitors are competitive inhibitors with respect to pantoic acid and possess submicromolar to micromolar inhibition constants. The observed SAR is rationalized through molecular docking studies based on the reported co-crystal structure of 1a with PanC. Finally, whole cell activity is assessed against wild-type Mtb as well as a PanC knockdown strain where PanC is depleted to less than 5% of wild-type levels. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.01.017

文献信息

• Reaction intermediate analogues as bisubstrate inhibitors of pantothenate synthetase
  作者：Zhixiang Xu、Wei Yin、Leonardo K. Martinelli、Joanna Evans、Jinglei Chen、Yang Yu、Daniel J. Wilson、Valerie Mizrahi、Chunhua Qiao、Courtney C. Aldrich

  DOI：10.1016/j.bmc.2014.01.017

  日期：2014.3

  The biosynthesis of pantothenate, the core of coenzyme A (CoA), has been considered an attractive target for the development of antimicrobial agents since this pathway is essential in prokaryotes, but absent in mammals. Pantothenate synthetase, encoded by the gene panC, catalyzes the final condensation of pantoic acid with beta-alanine to afford pantothenate via an intermediate pantoyl adenylate. We describe the synthesis and biochemical characterization of five PanC inhibitors that mimic the intermediate pantoyl adenylate. These inhibitors are competitive inhibitors with respect to pantoic acid and possess submicromolar to micromolar inhibition constants. The observed SAR is rationalized through molecular docking studies based on the reported co-crystal structure of 1a with PanC. Finally, whole cell activity is assessed against wild-type Mtb as well as a PanC knockdown strain where PanC is depleted to less than 5% of wild-type levels. (C) 2014 Elsevier Ltd. All rights reserved.