2-cyclopropyl-4-{1,4-dioxaspiro[4.5]decan-2-yl}-6-phenylpyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 2-cyclopropyl-4-{1,4-dioxaspiro[4.5]decan-2-yl}-6-phenylpyrimidine
• 英文别名: 2-Cyclopropyl-4-(1,4-dioxaspiro[4.5]decan-3-yl)-6-phenylpyrimidine；2-cyclopropyl-4-(1,4-dioxaspiro[4.5]decan-3-yl)-6-phenylpyrimidine
• 化学式: C₂₁H₂₄N₂O₂
• 分子量: 336.434
• InChiKey: OYQZZOHKHZHKOP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  44.2
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyclopropyl-4-{1,4-dioxaspiro[4.5]decan-2-yl}-6-phenylpyrimidine 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 以53%的产率得到1-(2-cyclopropyl-6-phenylpyrimidin-4-yl)ethane-1,2-diol
  参考文献：
  名称：

  DPD-Inspired Discovery of Novel LsrK Kinase Inhibitors: An Opportunity To Fight Antimicrobial Resistance

  摘要：

  Antibiotic resistance is posing a continuous threat to global public health and represents a huge burden for society as a whole. In the past decade, the interference with bacterial quorum sensing (QS) (i.e., cell cell communication) mechanisms has extensively been investigated as a valid therapeutic approach in the pursuit of a next generation of antimicrobials. (S)-4,5-Dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule that modulates QS in both Gram-negative and Gram-positive bacteria, is phosphorylated by LsrK, and the resulting phospho-DPD activates QS. We designed and prepared a small library of DPD derivatives, characterized by five different scaffolds, and evaluated their LsrK inhibition in the context of QS interference. SAR studies highlighted the pyrazole moiety as an essential structural element for LsrK inhibition. Particularly, four compounds were found to be micromolar LsrK inhibitors (IC50 ranging between 100 mu M and 500 mu M) encouraging further exploration of novel analogues as potential new antimicrobials.

  DOI：

  10.1021/acs.jmedchem.9b00025
• 作为产物：
  描述：

  苯甲酰氯 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 sodium carbonate decahydrate 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 生成 2-cyclopropyl-4-{1,4-dioxaspiro[4.5]decan-2-yl}-6-phenylpyrimidine
  参考文献：
  名称：

  DPD-Inspired Discovery of Novel LsrK Kinase Inhibitors: An Opportunity To Fight Antimicrobial Resistance

  摘要：

  Antibiotic resistance is posing a continuous threat to global public health and represents a huge burden for society as a whole. In the past decade, the interference with bacterial quorum sensing (QS) (i.e., cell cell communication) mechanisms has extensively been investigated as a valid therapeutic approach in the pursuit of a next generation of antimicrobials. (S)-4,5-Dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule that modulates QS in both Gram-negative and Gram-positive bacteria, is phosphorylated by LsrK, and the resulting phospho-DPD activates QS. We designed and prepared a small library of DPD derivatives, characterized by five different scaffolds, and evaluated their LsrK inhibition in the context of QS interference. SAR studies highlighted the pyrazole moiety as an essential structural element for LsrK inhibition. Particularly, four compounds were found to be micromolar LsrK inhibitors (IC50 ranging between 100 mu M and 500 mu M) encouraging further exploration of novel analogues as potential new antimicrobials.

  DOI：

  10.1021/acs.jmedchem.9b00025

文献信息

• DPD-Inspired Discovery of Novel LsrK Kinase Inhibitors: An Opportunity To Fight Antimicrobial Resistance
  作者：Silvia Stotani、Viviana Gatta、Prasanthi Medarametla、Mohan Padmanaban、Anna Karawajczyk、Fabrizio Giordanetto、Päivi Tammela、Tuomo Laitinen、Antti Poso、Dimitros Tzalis、Simona Collina

  DOI：10.1021/acs.jmedchem.9b00025

  日期：2019.3.14

  Antibiotic resistance is posing a continuous threat to global public health and represents a huge burden for society as a whole. In the past decade, the interference with bacterial quorum sensing (QS) (i.e., cell cell communication) mechanisms has extensively been investigated as a valid therapeutic approach in the pursuit of a next generation of antimicrobials. (S)-4,5-Dihydroxy-2,3-pentanedione, commonly known as (S)-DPD, a small signaling molecule that modulates QS in both Gram-negative and Gram-positive bacteria, is phosphorylated by LsrK, and the resulting phospho-DPD activates QS. We designed and prepared a small library of DPD derivatives, characterized by five different scaffolds, and evaluated their LsrK inhibition in the context of QS interference. SAR studies highlighted the pyrazole moiety as an essential structural element for LsrK inhibition. Particularly, four compounds were found to be micromolar LsrK inhibitors (IC50 ranging between 100 mu M and 500 mu M) encouraging further exploration of novel analogues as potential new antimicrobials.