1-O-(p-methoxyphenyl)-2-deoxy-2-trichloroacetamido-4,6-O-benzylidene-α-D-glucopyranose | 1140306-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: 1-O-(p-methoxyphenyl)-2-deoxy-2-trichloroacetamido-4,6-O-benzylidene-α-D-glucopyranose
• 英文别名: 1-O-(p-methoxyphenyl)-2-deoxy-2-trichloroacetamido-4,6-O-benzylidene-α-D-glucopyranoside；N-[(4aR,6R,7R,8R,8aS)-8-hydroxy-6-(4-methoxyphenoxy)-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-7-yl]-2,2,2-trichloroacetamide
• CAS: 1140306-70-2
• 化学式: C₂₂H₂₂Cl₃NO₇
• 分子量: 518.778
• InChiKey: YAPGYPBMKHSSDQ-NPKOBNKKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  95.5
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-O-(p-methoxyphenyl)-2-deoxy-2-trichloroacetamido-4,6-O-benzylidene-α-D-glucopyranose 、 2,3-di-O-acetyl-4-O-chloroacetyl-6-O-levulinoyl-β-D-glucopyranosyl trichloroacetimidate 以91%的产率得到[4-O-chloroacetyl-2,3-di-O-acetyl-6-O-levulinoyl-β-D-glucopyranosyl]-(1-3)-1-O-(p-methoxyphenyl)-2-deoxy-2-N-trichloroacetyl-4,6-O-benzylidene-α-D-glucopyranoside
  参考文献：
  名称：

  Novel synthetic gluco-disaccharide RSCL-0409 - a lipopolysaccharide-induced Toll-like receptor-mediated signalling antagonist

  摘要：

  The regulation of cytokines and pro‐inflammatory genes is an absolute essentiality to combat inflammatory diseases. The present study investigated the effects of 4‐O‐chloroacetyl‐2,3‐di‐O‐acetyl‐6‐O‐levulinoyl‐β‐d‐glucopyranosyl]‐(1‐3)‐1‐O‐(p‐methoxyphenyl)‐2‐deoxy‐2‐N‐trichloroacetyl‐4,6‐O‐benzylidene‐α‐d‐glucopyranoside (RSCL‐0409), a novel small molecule Toll‐like receptor (TLR) signalling antagonist, and its mechanism of action in human monocytic (THP‐1) cells stimulated with lipopolysaccharide (LPS). In THP‐1 and RAW264.7 cells, RSCL‐0409 suppressed LPS‐induced production of tumour necrosis factor‐α (TNF‐α) with a 50% inhibitory concentration of 10.6 μm and mRNA expression of ICAM‐1, Cox‐2 and interleukin‐8 with no evidence of cytotoxicity. RSCL‐0409 also suppressed TNF‐α production from LPS‐stimulated human peripheral blood mononuclear cells. Similar results were obtained in vivo in a murine model of LPS‐induced inflammation, where pretreatment with RSCL‐0409 resulted in significant inhibition of TNF‐α. It is also noteworthy that RSCL‐0409 suppressed the cytokine production induced by TLR2 and ‐4 ligands and not for any other TLR ligands. RSCL‐0409 significantly inhibited p65 nuclear translocation induced by LPS. In conclusion, RSCL‐0409, a novel small molecule, is the first of its kind in the category of carbohydrate‐derived TLR signalling antagonists and could definitely be a promising therapeutic agent for inflammatory diseases whose pathogenesis involves TLR2‐ or TLR4‐mediated signalling processes.

  DOI：

  10.1111/j.1742-4658.2010.07589.x
• 作为产物：
  描述：

  1-O-(p-methoxyphenyl)-2-deoxy-2-trichloroacetamido-α-D-glucopyranoside 、 苯甲醛二甲缩醛 在 对甲苯磺酸 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 以90%的产率得到1-O-(p-methoxyphenyl)-2-deoxy-2-trichloroacetamido-4,6-O-benzylidene-α-D-glucopyranose
  参考文献：
  名称：

  CARBOHYDRATE BASED TOLL-LIKE RECEPTOR (TLR) ANTAGONISTS

  摘要：

  该发明提供了基于碳水化合物的化合物、制备方法和组合物，用于调节通过Toll样受体的信号传导。该方法涉及将表达TLR的细胞与该发明的基于碳水化合物接触，其核心结构包括一个或多个糖基团。基于碳水化合物的化合物可用于抑制涉及TLR配体的免疫刺激，特别是TLR4和TLR2。这些化合物还适用于抑制由感染引起的炎症症状。这些化合物在治疗炎症、自身免疫、过敏、哮喘、移植排斥、移植物抗宿主病、感染、败血症、癌症和免疫缺陷方面有用。

  公开号：

  US20090215710A1