1-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine | 1153509-29-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 1-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine
• 英文别名: [(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)methyl](methyl)amine；1-(1-benzyl-3,5-dimethylpyrazol-4-yl)-N-methylmethanamine
• CAS: 1153509-29-5
• 化学式: C₁₄H₁₉N₃
• mdl: MFCD12403332
• 分子量: 229.325
• InChiKey: VFYDSXKZQQSZOY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.357
• 拓扑面积：
  29.8
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine 、 苯基缩水甘油醚 以 乙醇 为溶剂， 反应 22.0h， 以50%的产率得到1-(((1-Benzyl-3,5-dimethyl-1H-pyrazol-4-yl)methyl)(methyl)amino)-3-phenoxypropan-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：

  氯化苄 在 potassium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 20.25h， 生成 1-(1-benzyl-3,5-dimethyl-1H-pyrazol-4-yl)-N-methylmethanamine
  参考文献：
  名称：

  Discovery of novel small molecule TLR4 inhibitors as potent anti-inflammatory agents

  摘要：

  Toll-like receptor 4 (TLR4) initiates innate immune response to release inflammatory cytokines and has been pathologically linked to variety of inflammatory diseases. Recently, we found that Carvedilol, as the classic anti-heart failure and anti-inflammatory clinic drug, could inhibit the TLR4 signaling in the TLR4 overexpressed cells. Herein, we have designed and synthesized a small library of novel Carvedilol derivatives and investigated their potential inhibitory activity. The results indicate that the most potent compound 8a (SMU-XY3) could effectively inhibited TLR4 protein and the LPS triggered alkaline phosphatase signaling in HEK-Blue hTLR4 cells. It down regulated the nitric oxide (NO) in both RAW264.7 cells and BV-2 microglial cells, in addition to blocking the TNF-alpha signaling in ex-vivo human peripheral blood mononuclear cells (PBMC). More interestingly, 8a shows higher affinity to hyperpolarization-activated cyclic nucleotide-gated 4 (HCN4) over HCN2, which probably indicates the new application of TLR4 inhibitor 8a in heart failure, coronary heart disease, and other inflammatory diseases. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.05.033