(Z)-5-(benzo[d][1,3]dioxol-4-ylmethylene)imidazolidine-2,4-dione | 1256244-71-9

• 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-(benzo[d][1,3]dioxol-4-ylmethylene)imidazolidine-2,4-dione
• 英文别名: (Z)-5-(2,3-(methylenedioxy)phenyl)imidazolidine-2,4-dione；(Z)-5-(2,3-methylenedioxy-benzylidene)imidazolidine-2,4-dione；(5Z)-5-(1,3-benzodioxol-4-ylmethylidene)imidazolidine-2,4-dione
• CAS: 1256244-71-9
• 化学式: C₁₁H₈N₂O₄
• 分子量: 232.196
• InChiKey: PRECQMQTUBOIDD-DAXSKMNVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  76.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  海因 、 2,3-(亚甲二氧基)苯甲醛 在 C.I.酸性橙108 作用下， 以 水 、 乙醇 为溶剂， 以72%的产率得到(Z)-5-(benzo[d][1,3]dioxol-4-ylmethylene)imidazolidine-2,4-dione
  参考文献：
  名称：

  Discovery of Novel GSK-3β Inhibitors with Potent in Vitro and in Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-Based Virtual Screening

  摘要：

  Dysregulation of glycogen synthase kinase (GSK-3 beta) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3 beta yielded, from among compounds in our in-house database and two commercial databases, new GSK-3 beta inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.

  DOI：

  10.1021/jm100941j

文献信息

• Discovery of Novel GSK-3β Inhibitors with Potent in Vitro and in Vivo Activities and Excellent Brain Permeability Using Combined Ligand- and Structure-Based Virtual Screening
  作者：Mohammad A. Khanfar、Ronald A. Hill、Amal Kaddoumi、Khalid A. El Sayed

  DOI：10.1021/jm100941j

  日期：2010.12.23

  Dysregulation of glycogen synthase kinase (GSK-3 beta) is implicated in the pathophysiology of many diseases, including type-2 diabetes, stroke, Alzheimer's, and others. A multistage virtual screening strategy designed so as to overcome known caveats arising from the considerable flexibility of GSK-3 beta yielded, from among compounds in our in-house database and two commercial databases, new GSK-3 beta inhibitors with novel scaffold structures. The two most potent and selective validated hits, a 2-anilino-5-phenyl-1,3,4-oxadiazole (24) and a phenylmethylene hydantoin (28), both exhibited nanomolar affinity and selectivity over CDK2 and were potent enough for direct in vivo validation. Both were able to cause significant increases in liver glycogen accumulation in dose-dependent fashion. One also exhibited excellent blood-brain barrier permeability, the other adequate for a lead compound. Analogues of the oxadiazole 24 were synthesized to experimentally corroborate or rule out ligand-bound structures arising from docking studies. SAR results supported one docking study among a number of alternatives.
• US8188130B1
  申请人：——

  公开号：US8188130B1

  公开（公告）日：2012-05-29
• Phenylmethylene hydantoins as prostate cancer invasion and migration inhibitors. CoMFA approach and QSAR analysis
  作者：Mohammad A. Khanfar、Khalid A. El Sayed

  DOI：10.1016/j.ejmech.2010.08.066

  日期：2010.11

  Prostrate cancer constitutes the second leading cause of cancer deaths in men in United States. In the process of discovery of new antiproliferative and anti-metastatic agents against prostate cancer, marine-derived phenylmethylene hydantoin (PMH) derivatives were identified with activity level range between 50 and 200 mu M. 3D-QSAR CoMFA model was used in virtual screening of commercially available derivatives of PMH. PMH derivatives with manifold increase in anti-migratory and anti-invasive activities were discovered using wound-healing and Cultrex invasion assays. Benzene ring replacement with other heterocyclic rings did not significantly improve the methylene hydantoins activities. Multivariate analysis performed on the whole series of methylene hydantoins, which further supported the findings of CoMFA model. Predictive QSAR model with conventional r(2) and cross-validated coefficient (q(2)) values up to 0.982 and 0.803 were established. The molecular volume (MV) and the log P were identified as critical parameters for methylene hydatoins migration inhibitory activity. PMH is a novel anti-metastatic lead class with potential therapeutic activity against prostate cancer. (C) 2010 Elsevier Masson SAS. All rights reserved.