1-(4-(allyloxy)phenoxy)-3-(((3,5-dimethyl-1-(2-vinylbenzyl)-1H-pyrazol-4-yl)methyl)(methyl)amino)propan-2-ol | 1280193-93-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(4-(allyloxy)phenoxy)-3-(((3,5-dimethyl-1-(2-vinylbenzyl)-1H-pyrazol-4-yl)methyl)(methyl)amino)propan-2-ol
• 英文别名: 1-[[1-[(2-Ethenylphenyl)methyl]-3,5-dimethylpyrazol-4-yl]methyl-methylamino]-3-(4-prop-2-enoxyphenoxy)propan-2-ol
• CAS: 1280193-93-2
• 化学式: C₂₈H₃₅N₃O₃
• 分子量: 461.604
• InChiKey: VYEMMWLYLIPJES-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  59.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-(allyloxy)phenoxy)-3-(((3,5-dimethyl-1-(2-vinylbenzyl)-1H-pyrazol-4-yl)methyl)(methyl)amino)propan-2-ol 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 作用下， 以 甲苯 为溶剂， 反应 7.0h， 以52%的产率得到(4Z)-15,18,28-trimethyl-2,22-dioxa-13,14,18-triazatetracyclo[21.2.2.113,16.06,11]octacosa-1(26),4,6,8,10,14,16(28),23(27),24-nonaen-20-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-丙烯氧基苯酚 在 sodium hydride 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 140.0 ℃ 、500.01 kPa 条件下， 反应 0.58h， 生成 1-(4-(allyloxy)phenoxy)-3-(((3,5-dimethyl-1-(2-vinylbenzyl)-1H-pyrazol-4-yl)methyl)(methyl)amino)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

文献信息

• Method for Treating Scleroderma
  申请人：The Regents of the University of Colorado, A body corporate

  公开号：US20150087682A1

  公开（公告）日：2015-03-26

  The present invention provides a method for treating scleroderma by administering a therapeutically effective amount of a toll like receptor 4 inhibitor to a subject in need of such a treatment.

  本发明提供了一种治疗硬皮病的方法，通过向需要此类治疗的受试者施用治疗有效量的Toll样受体4抑制剂。
• TOLL-LIKE RECEPTOR MODULATORS AND USES THEREOF
  申请人：Yin Hang

  公开号：US20120178774A1

  公开（公告）日：2012-07-12

  The present invention provides a compound selected from the group consisting of: where n, m, X 1 , X 2 , X 3 , X 4 , R 1 , R 2 , R 3 , R 11 , R 12 , Y 1 , Y 2 , Y 3 , Y 4 , and Y 5 are those defined herein. Some aspects of the invention also provides methods for using these compounds and compositions comprising the same.

  本发明提供了从以下组中选择的化合物：其中n，m，X1，X2，X3，X4，R1，R2，R3，R11，R12，Y1，Y2，Y3，Y4和Y5如本文所定义。本发明的某些方面还提供了使用这些化合物的方法和包含它们的组合物。
• US8642614B2
  申请人：——

  公开号：US8642614B2

  公开（公告）日：2014-02-04
• [EN] METHOD TREATING SCLERODERMA<br/>[FR] PROCÉDÉ DE TRAITEMENT DE LA SCLÉRODERMIE
  申请人：UNIV COLORADO REGENTS

  公开号：WO2013158698A2

  公开（公告）日：2013-10-24

  The present invention provides a method for treating scleroderma by administering a therapeutically effective amount of a toll like receptor 4 inhibitor to a subject in need of such a treatment.
• 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.