(S)-5-methyl-1-(1-(3-phenoxybenzyl)piperidin-3-yl)pyrimidine-2,4(1H,3H)-dione | 1403670-15-4

• 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: (S)-5-methyl-1-(1-(3-phenoxybenzyl)piperidin-3-yl)pyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-methyl-1-[(3~{S})-1-[(3-phenoxyphenyl)methyl]piperidin-3-yl]pyrimidine-2,4-dione；5-methyl-1-[(3S)-1-[(3-phenoxyphenyl)methyl]piperidin-3-yl]pyrimidine-2,4-dione
• CAS: 1403670-15-4
• 化学式: C₂₃H₂₅N₃O₃
• 分子量: 391.47
• InChiKey: UVSXXFBEAJISCP-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 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：

  (S)-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 (S)-5-methyl-1-(1-(3-phenoxybenzyl)piperidin-3-yl)pyrimidine-2,4(1H,3H)-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

文献信息

• Elaboration of a proprietary thymidylate kinase inhibitor motif towards anti-tuberculosis agents
  作者：Lijun Song、Martijn D.P. Risseeuw、Matheus Froeyen、Izet Karalic、Jan Goeman、Davie Cappoen、Johan Van der Eycken、Paul Cos、Hélène Munier-Lehmann、Serge Van Calenbergh

  DOI：10.1016/j.bmc.2016.08.041

  日期：2016.11

  We report the design and synthesis of a series of non-nucleoside MtbTMPK inhibitors (1–14) based on the gram-positive bacterial TMPK inhibitor hit compound 1. A practical synthesis was developed to access these analogues. Several compounds show promising MtbTMPK inhibitory potency and allow the establishment of a structure–activity relationship, which is helpful for further optimization.

  我们报告了基于革兰氏阳性细菌TMPK抑制剂命中化合物1的一系列非核苷Mtb TMPK抑制剂的设计和合成（1 – 14）。开发了实用的合成方法以访问这些类似物。几种化合物显示出有希望的Mtb TMPK抑制潜能，并可以建立结构-活性关系，这有助于进一步优化。