2-(3-chlorophenoxy)-4-[(1R)-2-cyclohexyl-1-[(3S)-3-(5-methyl-2,4-dioxopyrimidin-1-yl)piperidin-1-yl]ethyl]benzoic acid | 1403670-51-8

• 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: 2-(3-chlorophenoxy)-4-[(1R)-2-cyclohexyl-1-[(3S)-3-(5-methyl-2,4-dioxopyrimidin-1-yl)piperidin-1-yl]ethyl]benzoic acid
• CAS: 1403670-51-8
• 化学式: C₃₁H₃₆ClN₃O₅
• 分子量: 566.097
• InChiKey: KIAAPOUCAAGGMQ-RPLLCQBOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  40
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  环己基乙酰氯 在 sodium tetrahydroborate 、 四(三苯基膦)钯 、 水 、 potassium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 、 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 58.5h， 生成 2-(3-chlorophenoxy)-4-[(1R)-2-cyclohexyl-1-[(3S)-3-(5-methyl-2,4-dioxopyrimidin-1-yl)piperidin-1-yl]ethyl]benzoic acid 、 2-(3-chlorophenoxy)-4-((S)-2-cyclohexyl-1-((S)-3-(5-methyl-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)piperidin-1-yl)ethyl)benzoic acid
  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