3'-O-(tert-butyldimethylsilyl)-5'-O-{N-[(R)-2-(tert-butyldimethylsilyloxy)-3,3-dimethylbutanoyl]sulfamoyl}-2'-deoxy-2'-fluoroadenosine triethylammonium salt | 1606136-70-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物
• 英文名称: 3'-O-(tert-butyldimethylsilyl)-5'-O-{N-[(R)-2-(tert-butyldimethylsilyloxy)-3,3-dimethylbutanoyl]sulfamoyl}-2'-deoxy-2'-fluoroadenosine triethylammonium salt
• CAS: 1606136-70-2
• 化学式: C₆H₁₅N*C₂₈H₅₁FN₆O₇SSi₂
• 分子量: 792.176
• InChiKey: FLQBPQAXYYWKHU-LHSSCAJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  52.0
• 可旋转键数：
  13.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.82
• 拓扑面积：
  173.02
• 氢给体数：
  2.0
• 氢受体数：
  13.0

反应信息

• 作为反应物：
  描述：

  3'-O-(tert-butyldimethylsilyl)-5'-O-{N-[(R)-2-(tert-butyldimethylsilyloxy)-3,3-dimethylbutanoyl]sulfamoyl}-2'-deoxy-2'-fluoroadenosine triethylammonium salt 在 三氟乙酸 作用下， 以 水 为溶剂， 反应 72.0h， 以5 mg的产率得到2'-deoxy-2'-fluoro-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
• 作为产物：
  描述：

  阿糖腺苷 在 吡啶 、 二乙胺基三氟化硫 、 sodium hydride 、 caesium carbonate 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 44.33h， 生成 3'-O-(tert-butyldimethylsilyl)-5'-O-{N-[(R)-2-(tert-butyldimethylsilyloxy)-3,3-dimethylbutanoyl]sulfamoyl}-2'-deoxy-2'-fluoroadenosine triethylammonium salt
  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