(Z)-5-(4-(methylthio)benzylidene)-hydantoin | 1189518-78-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (Z)-5-(4-(methylthio)benzylidene)-hydantoin
• 英文别名: (Z)-5-(4-(methylthio)-benzylidene)imidazolidine-2,4-dione；(Z)-5-(4-(methylthio)benzylidene)imidazolidine-2,4-dione；(5Z)-5-[(4-methylsulfanylphenyl)methylidene]imidazolidine-2,4-dione
• CAS: 1189518-78-2
• 化学式: C₁₁H₁₀N₂O₂S
• 分子量: 234.279
• InChiKey: XTMVUGQFVUETDJ-TWGQIWQCSA-N

物化性质

• 溶解度：
  9.8 [ug/mL]

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  83.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  海因 、 4-(甲基巯基)苯甲醛 在 碳酸氢钠 、 C.I.酸性橙108 作用下， 以 乙醇 、 水 为溶剂， 生成 (Z)-5-(4-(methylthio)benzylidene)-hydantoin
  参考文献：
  名称：

  The marine natural-derived inhibitors of glycogen synthase kinase-3β phenylmethylene hydantoins: In vitro and in vivo activities and pharmacophore modeling

  摘要：

  The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1). This natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)- hydantoin (2) showed potent in vitro and in vivo anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT, spheroid disaggregation, and in mice models. To explore a possible molecular target of PMHs, the most potent synthetic analogue 2 has been virtually screened against various protein kinases. Molecular modeling study has shown that 2 can be successfully docked within the binding pocket of glycogen synthase kinase-3 beta (GSK-3 beta) similar to the well-known GSK-3 beta inhibitor 1-5. Several PMHs showed potent in vitro GSK-3b inhibitory activity with an IC50 range of 4-20 mu M. The most potent analogue 3 showed a significant increase in liver glycogen level at the 5, 15, and 25 mg/kg dose levels, in vivo. Pharmacophore model was built and validated using in-house database of active and inactive GSK-3b inhibitors. The GSK-3b inhibitory activity of PMHs entitles them to be potential leads for the treatment of cancer, Alzheimer's disease, bipolar disorders, stroke, different tau pathologies, and type-2 diabetes. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2009.06.054

文献信息

• US8188130B1
  申请人：——

  公开号：US8188130B1

  公开（公告）日：2012-05-29
• The marine natural-derived inhibitors of glycogen synthase kinase-3β phenylmethylene hydantoins: In vitro and in vivo activities and pharmacophore modeling
  作者：Mohammad A. Khanfar、Bilal Abu Asal、Mudit Mudit、Amal Kaddoumi、Khalid A. El Sayed

  DOI：10.1016/j.bmc.2009.06.054

  日期：2009.8

  The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1). This natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)- hydantoin (2) showed potent in vitro and in vivo anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT, spheroid disaggregation, and in mice models. To explore a possible molecular target of PMHs, the most potent synthetic analogue 2 has been virtually screened against various protein kinases. Molecular modeling study has shown that 2 can be successfully docked within the binding pocket of glycogen synthase kinase-3 beta (GSK-3 beta) similar to the well-known GSK-3 beta inhibitor 1-5. Several PMHs showed potent in vitro GSK-3b inhibitory activity with an IC50 range of 4-20 mu M. The most potent analogue 3 showed a significant increase in liver glycogen level at the 5, 15, and 25 mg/kg dose levels, in vivo. Pharmacophore model was built and validated using in-house database of active and inactive GSK-3b inhibitors. The GSK-3b inhibitory activity of PMHs entitles them to be potential leads for the treatment of cancer, Alzheimer's disease, bipolar disorders, stroke, different tau pathologies, and type-2 diabetes. (C) 2009 Elsevier Ltd. All rights reserved.