(Z)-5-(4-(diethylamino)benzylidene)imidazolidine-2,4-dione

• 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-(diethylamino)benzylidene)imidazolidine-2,4-dione
• 英文别名: (5Z)-5-[[4-(diethylamino)phenyl]methylidene]imidazolidine-2,4-dione
• 化学式: C₁₄H₁₇N₃O₂
• 分子量: 259.308
• InChiKey: QSFFDFDTLWXQFV-XFXZXTDPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  19
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  海因 、 N,N-二乙基-4-氨基苯甲醛 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-(diethylamino)benzylidene)imidazolidine-2,4-dione
  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

• [EN] NOVEL N3-AMINOALKYL DERIVATIVES OF 5-ARYLIDENEHYDANTOIN, PHARMACEUTICAL COMPOSITION CONTAINING THE ABOVE AND APPLICATION THEREOF<br/>[FR] NOUVEAUX DÉRIVÉS N3-AMINOALKYLE DE 5-ARYLIDÈNEHYDANTOÏNE, COMPOSITION PHARMACEUTIQUE CONTENANT CES DERNIERS ET APPLICATION ASSOCIÉE
  申请人：UNIWERSYTET JAGIELLOŃSKI

  公开号：WO2015065212A1

  公开（公告）日：2015-05-07

  The invention discloses novel 3-aminoalkyl derivatives of 5-arylidenehydantoin of formula I, pharmaceutical composition containing these derivatives and the use thereof in inhibition of efflux of drugs used to prevent and treat diseases of bacterial and/or cancer origin.

  本发明公开了式I的新型5-芳基亚醰基脲的3-氨基烷基衍生物，包含这些衍生物的药物组合物以及将其用于抑制用于预防和治疗细菌和/或癌症起源疾病的药物外流的用途。
• Anticonvulsant Activity of Phenylmethylenehydantoins:  A Structure−Activity Relationship Study
  作者：Jeyanthi Chinnappa Thenmozhiyal、Peter Tsun-Hon Wong、Wai-Keung Chui

  DOI：10.1021/jm030450c

  日期：2004.3.1

  Phenylmethylenehydantoins (PMHs) and their des-phenyl analogues were synthesized and evaluated for anticonvulsant activity using the maximal electroshock seizure (MES) assay. The phenyl rings of PMHs were substituted with a wide spectrum of groups, and the selection of substituents was guided by Craig's plot. Phenylmethylenehydantoins substituted with alkyl (2, 3, 5, 6, 12, 14), halogeno (35, 38, 41), trifluoromethyl (11), and alkoxyl (23) groups at the phenyl ring were found to exhibit good anticonvulsant activity with EDMES(2.5) ranging from 28 to 90 mg/kg. Substitution of polar groups such as -NO2, -CN, and -OH was found to be less active or inactive on PMHs. Replacement of the phenyl ring with heteroaromatic rings reduced or caused the loss of anticonvulsant activity. The study identified two PMHs, 14 (EDMES(2.5) = 28 +/- 2 mg/kg) and 12 (EDMES(2.5) = 39 4 mg/kg), to be the most active candidates of the series, which are comparable to phenytoin (55, EDMES(2.5) = 30 +/- 2 mg/kg) in their protection against seizure. Multivariate analysis performed on the whole series of 54 PMHs further supported the finding that the alkylated phenylmethylenehydantoins are the best acting compounds. The SAR model derived on the basis of 12 of the most active phenylmethylenehydantoins demonstrated good predicting ability (root-mean-square error of prediction (RMSEP) = 0.134; RMSEE = 0.057) and identified LUMO energy and the log P as critical parameters for their anticonvulsant activity.
• 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.