(R)-2-((4-ethoxyphenoxy)methyl)oxirane | 1227743-95-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (R)-2-((4-ethoxyphenoxy)methyl)oxirane
• 英文别名: (2R)-2-[(4-ethoxyphenoxy)methyl]oxirane
• CAS: 1227743-95-4
• 化学式: C₁₁H₁₄O₃
• 分子量: 194.23
• InChiKey: RXBYVUJCNJKSEO-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  31
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-2-((4-ethoxyphenoxy)methyl)oxirane 、 1-(1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine 在 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 48.0h， 以57%的产率得到(R)-1-(((1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)methyl)(methyl)amino)-3-(4-ethoxyphenoxy)propan-2-ol
  参考文献：
  名称：

  Development of β-Amino Alcohol Derivatives That Inhibit Toll-like Receptor 4 Mediated Inflammatory Response as Potential Antiseptics

  摘要：

  Toll-like receptor 4 (TLR4) induced proinflammatory signaling has been directly implicated in severe sepsis and represents an attractive therapeutic target. Herein, we report our investigations into the structure-activity relationship and preliminary drug metabolism/pharmacokinetics study of beta-amino alcohol derivatives that inhibit the TLR4 signaling pathway. Lead compounds were identified from in vitro cellular examination with micromolar potency for their inhibitory effects on TLR4 signaling and subsequently assessed for their ability to suppress the TLR4-induced inflammatory response in an ex vivo whole blood model. In addition, the toxicology, specificity, solubility, brain-blood barrier permeability, and drug metabolism of several compounds were evaluated. Although further optimizations are needed, our findings lay the groundwork for the future drug development of this class of small molecule agents for the treatment of severe sepsis.

  DOI：

  10.1021/jm2003365
• 作为产物：
  描述：

  4-乙氧基苯酚 在 (S,S)-(+)-N,N'-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminocobalt(II) 、 水 、 potassium carbonate 、 溶剂黄146 作用下， 以 四氢呋喃 、 二氯甲烷 、 丙酮 为溶剂， 反应 64.33h， 生成 (R)-2-((4-ethoxyphenoxy)methyl)oxirane
  参考文献：
  名称：

  Development of β-Amino Alcohol Derivatives That Inhibit Toll-like Receptor 4 Mediated Inflammatory Response as Potential Antiseptics

  摘要：

  Toll-like receptor 4 (TLR4) induced proinflammatory signaling has been directly implicated in severe sepsis and represents an attractive therapeutic target. Herein, we report our investigations into the structure-activity relationship and preliminary drug metabolism/pharmacokinetics study of beta-amino alcohol derivatives that inhibit the TLR4 signaling pathway. Lead compounds were identified from in vitro cellular examination with micromolar potency for their inhibitory effects on TLR4 signaling and subsequently assessed for their ability to suppress the TLR4-induced inflammatory response in an ex vivo whole blood model. In addition, the toxicology, specificity, solubility, brain-blood barrier permeability, and drug metabolism of several compounds were evaluated. Although further optimizations are needed, our findings lay the groundwork for the future drug development of this class of small molecule agents for the treatment of severe sepsis.

  DOI：

  10.1021/jm2003365

文献信息

• Selection, Preparation, and Evaluation of Small-Molecule Inhibitors of Toll-Like Receptor 4
  作者：Douglas E. Bevan、Alexander J. Martinko、Lisa C. Loram、Joshua A. Stahl、Frederick R. Taylor、Sampada Joshee、Linda R. Watkins、Hang Yin

  DOI：10.1021/ml100041f

  日期：2010.8.12

  Toll-like receptor 4 (TLR4), a membrane-spanning receptor protein that functions in complex with its accessory protein MD-2, is an intriguing target for therapeutic development. Herein, we report the identification of a series of novel TLR4 inhibitors and the development of a robust, enantioselective synthesis using an unprecedented Mannich type reaction to functionalize a pyrazole ring. In silico and cellular assay results demonstrated that compound 1 and its analogues selectively block TLR4 activation in live cells. Animal model tests showed that 1 and its derivatives could potentiate morphine-induced analgesia in vivo, presumably by attenuating the opioid-induced TLR4 activation.
• Development of β-Amino Alcohol Derivatives That Inhibit Toll-like Receptor 4 Mediated Inflammatory Response as Potential Antiseptics
  作者：Sherry A. Chavez、Alexander J. Martinko、Corinna Lau、Michael N. Pham、Kui Cheng、Douglas E. Bevan、Tom E. Mollnes、Hang Yin

  DOI：10.1021/jm2003365

  日期：2011.7.14

  Toll-like receptor 4 (TLR4) induced proinflammatory signaling has been directly implicated in severe sepsis and represents an attractive therapeutic target. Herein, we report our investigations into the structure-activity relationship and preliminary drug metabolism/pharmacokinetics study of beta-amino alcohol derivatives that inhibit the TLR4 signaling pathway. Lead compounds were identified from in vitro cellular examination with micromolar potency for their inhibitory effects on TLR4 signaling and subsequently assessed for their ability to suppress the TLR4-induced inflammatory response in an ex vivo whole blood model. In addition, the toxicology, specificity, solubility, brain-blood barrier permeability, and drug metabolism of several compounds were evaluated. Although further optimizations are needed, our findings lay the groundwork for the future drug development of this class of small molecule agents for the treatment of severe sepsis.