N,N'-bis[3,5-bis[(Z)-N-(diaminomethylideneamino)-C-methylcarbonimidoyl]phenyl]decanediamide;tetrahydrochloride | 164301-51-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N,N'-bis[3,5-bis[(Z)-N-(diaminomethylideneamino)-C-methylcarbonimidoyl]phenyl]decanediamide;tetrahydrochloride
• CAS: 164301-51-3
• 化学式: C34H56Cl4N18O2
• 分子量: 890.7
• InChiKey: MAHASPGBAIQZLY-MTJUHGJCSA-N

物化性质

• 溶解度：
  溶于二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.06
• 重原子数：
  58
• 可旋转键数：
  19
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  365
• 氢给体数：
  14
• 氢受体数：
  10

制备方法与用途

生物活性

Semapimod tetrahydrochloride (CNI-1493) 是促炎细胞因子产生 (proinflammatory cytokine) 的抑制剂，可抑制TNF-α、IL-1β 和 IL-6。Semapimod tetrahydrochloride 抑制巨噬细胞 p38 MAPK 和一氧化氮生成。Semapimod tetrahydrochloride 抑制 TLR4 信号 (IC50≈0.3 μM)。Semapimod tetrahydrochloride 在多种炎症和自身免疫性疾病中具有潜在的作用。

靶点

IL-1β

IL-6

TNF-α

p38 MAPK

体外研究

Semapimod tetrahydrochloride leads to a significant decrease of p38-MAPK phosphorylation in macrophages, proinflammatory gene expression of macrophage inflammatory protein-1alpha, interleukin-6, monocyte chemoattractant protein-1, and intercellular adhesion molecule-1, and neutrophil infiltration. Semapimod tetrahydrochloride completely abrogated nitric oxide production within the tunica muscularis.
Semapimod tetrahydrochloride desensitizes TLR signaling via its effect on the TLR chaperone gp96. Semapimod tetrahydrochloride inhibits ATP-binding and ATPase activities of gp96 in vitro (IC ₅₀ ≈0.2-0.4 μM). Semapimod tetrahydrochloride desensitizes TLR signaling via its effect on the TLR chaperone gp96.

体内研究

Semapimod tetrahydrochloride (5 mg/kg; i.p; daily for 2 weeks) ameliorates endothelial dysfunction in Obese Zucker (OZ) rats.
Semapimod tetrahydrochloride restores AM-induced akt phosphorylation and cGMP production in OZ rats.

Animal Model:	Male OZ rats
Dosage:	5 mg/kg
Administration:	I.p; daily for 2 weeks
Result:	Restored endothelium-dependent vasorelaxation in OZ rats.