1-[(3R)-1-[[3-(3,4-dichlorophenoxy)phenyl]methyl]piperidin-3-yl]-5-methylpyrimidine-2,4-dione | 1403670-33-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 1-[(3R)-1-[[3-(3,4-dichlorophenoxy)phenyl]methyl]piperidin-3-yl]-5-methylpyrimidine-2,4-dione
• CAS: 1403670-33-6
• 化学式: C₂₃H₂₃Cl₂N₃O₃
• 分子量: 460.36
• InChiKey: JSQCTKVQHZBGSD-QGZVFWFLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (R)-tert-butyl (3-3-(((2E)-3-methoxy-2-methylprop-2-enoyl)carbamoyl)amino)piperidine-1-carboxylate 在 硫酸 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 溶剂黄146 为溶剂， 反应 32.0h， 生成 1-[(3R)-1-[[3-(3,4-dichlorophenoxy)phenyl]methyl]piperidin-3-yl]-5-methylpyrimidine-2,4-dione
  参考文献：
  名称：

  Discovery of Selective and Potent Inhibitors of Gram-Positive Bacterial Thymidylate Kinase (TMK)

  摘要：

  Thymidylate kinase (TMK) is an essential enzyme in bacterial DNA synthesis. The deoxythymidine monophosphate (dTMP) substrate binding pocket was targeted in rational-design, structure-supported effort, yielding a unique series of antibacterial agents showing a novel, induced-fit binding mode. Lead optimization, aided by X-ray crystallography, led to picomolar inhibitors of both Streptococcus pneumoniae and Staphylococcus aureus TMK. MICs < 1 mu g/mL were achieved against methicillin-resistant S. aureus (MRSA), S. pneumoniae, and vancomycin-resistant. Enterococcus (VRE). Log D adjustments yielded single diastereomers 14 (TK-666) and 46, showing a broad antibacterial spectrum against Gram-positive bacteria and excellent selectivity against the human thymidylate kinase ortholog.

  DOI：

  10.1021/jm3011806