4-nitrophenyl-[((4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl)methyl]sulfamate | 1572039-78-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4-nitrophenyl-[((4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl)methyl]sulfamate
• CAS: 1572039-78-1
• 化学式: C₁₉H₂₂N₂O₇S
• 分子量: 422.459
• InChiKey: UKJVVMODHGCEKQ-ZENAZSQFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.95
• 重原子数：
  29.0
• 可旋转键数：
  7.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  117.0
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-nitrophenyl-[((4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl)methyl]sulfamate 、 5-氨基-5-脱氧-2,3-O-(1-甲基亚乙基)-腺苷酸 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 以100 mg的产率得到5'-amino-5'-deoxy-5'-N-(N-{[(2R,4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl]methylamino}sulfamoyl)-2',3'-O-isopropylideneadenosine
  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：

  (4R)-4-azidomethyl-5,5-dimethyl-2-phenyl-1,3-dioxane 在 对硝基苯酚 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 4-nitrophenyl-[((4R)-5,5-dimethyl-2-phenyl-1,3-dioxan-4-yl)methyl]sulfamate
  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