SKI-I-Asp | 1245919-41-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: SKI-I-Asp
• 英文别名: 1H-Pyrazole-3-carboxylic acid, 5-(2-naphthalenyl)-, 2-[[2-[[2-(acetyloxy)benzoyl]oxy]-1-naphthalenyl]methylene]hydrazide；[1-[[(5-naphthalen-2-yl-1H-pyrazole-3-carbonyl)hydrazinylidene]methyl]naphthalen-2-yl] 2-acetyloxybenzoate
• CAS: 1245919-41-8
• 化学式: C₃₄H₂₄N₄O₅
• 分子量: 568.588
• InChiKey: ICQQXCFFGHOVQV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  43
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.03
• 拓扑面积：
  123
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-naphthalen-2-yl-1H-pyrazol-3-carboxylic acid hydrazide 、 1-formyl-2-(2-acetoxybenzoyloxy)naphthalene 在 溶剂黄146 作用下， 以 二甲基亚砜 为溶剂， 以67%的产率得到SKI-I-Asp
  参考文献：
  名称：

  Synthesis and bioactivity of sphingosine kinase inhibitors and their novel aspirinyl conjugated analogs

  摘要：

  Sphingosine kinase (SphK) is a lipid kinase with oncogenic activity, and SphK inhibitors (SKIS) are known for their anti-cancer activity. Here, we report highly efficient syntheses of SKIs and their aspirinyl (Asp) analogs. Both SKIs and their Asp analogs were highly cytotoxic towards multiple human cancer cell lines: in several cases the Asp analogs were up to three times more effective. Furthermore, they were equally potent inhibitors of SphK. The pharmacokinetic study indicated that SKI-I-Asp cleaved efficiently to form SKI-I and the half-life of SKI-I was increased from similar to 7 h in SKI-I to similar to 10 h in SKI-I-Asp injected mice, thereby prolonging its effect. In summary, the Asp-conjugated SKIs seem to be promising prodrugs of SKIs where delivery in vivo remains a problem. (C) 2010 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.06.005