SKI-II-Asp | 1245919-42-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 缩酚酸和缩酚酸环醚类
• 英文名称: SKI-II-Asp
• 英文别名: Benzoic acid, 2-(acetyloxy)-, 4-[[4-(4-chlorophenyl)-2-thiazolyl]amino]phenyl ester；[4-[[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino]phenyl] 2-acetyloxybenzoate
• CAS: 1245919-42-9
• 化学式: C₂₄H₁₇ClN₂O₄S
• 分子量: 464.929
• InChiKey: VDQXNBDUQMASBI-UHFFFAOYSA-N

物化性质

• 沸点：
  644.3±65.0 °C(Predicted)
• 密度：
  1.381±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.04
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  4-[[4-(4-氯苯基)-2-噻唑基]氨基]苯酚 、 邻乙酰水杨酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以70.7%的产率得到SKI-II-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

文献信息

• Synthesis and bioactivity of sphingosine kinase inhibitors and their novel aspirinyl conjugated analogs
  作者：Arun K. Sharma、Ugir Hossain Sk、Melissa A. Gimbor、Jeremy A. Hengst、Xujun Wang、Jong Yun、Shantu Amin

  DOI：10.1016/j.ejmech.2010.06.005

  日期：2010.9

  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.