4-((9H-carbazol-4-yl)oxy)-1-(((1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)methyl) (methyl)amino)butan-2-ol

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 4-((9H-carbazol-4-yl)oxy)-1-(((1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)methyl) (methyl)amino)butan-2-ol
• 英文别名: 4-(9H-carbazol-4-yloxy)-1-[[1-[(2-chlorophenyl)methyl]-3,5-dimethylpyrazol-4-yl]methyl-methylamino]butan-2-ol
• 化学式: C₃₀H₃₃ClN₄O₂
• 分子量: 517.071
• InChiKey: JMJWLUAPSNGOOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  37
• 可旋转键数：
  10
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  66.3
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-羟基咔唑 在 sodium hydroxide 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 48.0h， 生成 4-((9H-carbazol-4-yl)oxy)-1-(((1-(2-chlorobenzyl)-3,5-dimethyl-1H-pyrazol-4-yl)methyl) (methyl)amino)butan-2-ol
  参考文献：
  名称：

  一种咔唑β-氨基醇类衍生物及其制备方法和 用途

  摘要：

  本发明涉及一种咔唑β‑氨基醇类衍生物，其药物组合物、制备方法及用途。本发明化合物能够有效的抑制toll样受体4的活性及水平和对HCN通道亚型有抑制作用，其中具体公开了6种化合物，并公开了所述的化合物及其可药用接受的盐在制备TLR4受体抑制剂及应用为佐剂、抗炎、肿瘤免疫等方面的应用。其结构如下式所示：其中R1为取代的卤素原子、氨基、硝基、C1‑6烷基、C1‑6烷氧基，和C1‑6烷基中任意一个或多个取代基所取代，R2为取代的H，卤素原子、氨基、硝基、C1‑6烷基、C1‑6烷氧基，和C1‑6烷基中任意一个或多个取代基所取代。n为1，2，3或4。

  公开号：

  CN109867662B

文献信息

• Discovery of novel small molecule TLR4 inhibitors as potent anti-inflammatory agents
  作者：Yao Xu、Shujun Chen、Ying Cao、Pingzheng Zhou、Zhipeng Chen、Kui Cheng

  DOI：10.1016/j.ejmech.2018.05.033

  日期：2018.6

  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.