Z-4-ethylthio-phenylmethylene hydantoin | 1134426-32-6

• 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-4-ethylthio-phenylmethylene hydantoin
• 英文别名: (Z)-5-(4-(ethylthio)benzylidene)imidazolidine-2,4-dione；(5Z)-5-[(4-ethylsulfanylphenyl)methylidene]imidazolidine-2,4-dione
• CAS: 1134426-32-6
• 化学式: C₁₂H₁₂N₂O₂S
• 分子量: 248.305
• InChiKey: UWMDBDYLNJITCD-YFHOEESVSA-N

物化性质

• 密度：
  1.33±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 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-(乙基硫代)苯甲醛 在 碳酸氢钠 、 C.I.酸性橙108 作用下， 以 水 、 乙醇 为溶剂， 反应 10.0h， 生成 Z-4-ethylthio-phenylmethylene hydantoin
  参考文献：
  名称：

  (Phenylmethylidene)-乙内酰脲作为前列腺癌迁移抑制剂的优化：SAR 导向设计、合成和药效团建模

  摘要：

  前列腺癌是西方国家男性中最常见的癌症形式之一。天然产物被证明是分子多样性的无与伦比的来源。4-(羟基苯亚甲基)乙内酰脲 (PMH; 1), (5Z)-5-(4-hydroxybenzylidene)imidazolidine-2,4-dione，从红海海绵半真菌阿拉比卡中分离出来，最近显示出连接复合物的稳定性，抗-体外和体内的侵入性和抗转移活性。相关的合成类似物，(5Z)-5-[4-(乙基硫烷基)苯亚甲基]咪唑烷-2,4-二酮 (2)，显示出对高侵袭性前列腺癌的体内抗转移特性提高了数倍。为了进一步优化 PMH 的活性，使用了各种基于配体的策略，包括结构扩展、结构简化、接头扩展、和计算机辅助的 CoMFA（比较分子场分析）结果。这些策略产生了 30 种基于第一代 PMH 设计的第二代 PMH，例如 1 和 2。选择伤口愈合试验来评估这些新 PMH 对 PC-3 细胞系的体外抗迁移潜力. 确定了几种活性

  DOI：

  10.1002/cbdv.201000248

文献信息

• Optimization of (Phenylmethylidene)-hydantoins as Prostate Cancer Migration Inhibitors: SAR-Directed Design, Synthesis, and Pharmacophore Modeling
  作者：Mudit Mudit、Khalid A. El Sayed

  DOI：10.1002/cbdv.201000248

  日期：2011.8

  properties against the highly invasive prostate cancer. To further optimize the activity of PMHs, various ligand‐based strategies were used including the extension of the structure, structural simplification, linker extension, and computer‐assisted CoMFA (Comparative Molecular Field Analysis) results. These strategies yielded thirty 2nd‐generation PMHs, designed based on the 1st‐generation PMHs, such

  前列腺癌是西方国家男性中最常见的癌症形式之一。天然产物被证明是分子多样性的无与伦比的来源。4-(羟基苯亚甲基)乙内酰脲 (PMH; 1), (5Z)-5-(4-hydroxybenzylidene)imidazolidine-2,4-dione，从红海海绵半真菌阿拉比卡中分离出来，最近显示出连接复合物的稳定性，抗-体外和体内的侵入性和抗转移活性。相关的合成类似物，(5Z)-5-[4-(乙基硫烷基)苯亚甲基]咪唑烷-2,4-二酮 (2)，显示出对高侵袭性前列腺癌的体内抗转移特性提高了数倍。为了进一步优化 PMH 的活性，使用了各种基于配体的策略，包括结构扩展、结构简化、接头扩展、和计算机辅助的 CoMFA（比较分子场分析）结果。这些策略产生了 30 种基于第一代 PMH 设计的第二代 PMH，例如 1 和 2。选择伤口愈合试验来评估这些新 PMH 对 PC-3 细胞系的体外抗迁移潜力. 确定了几种活性
• 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.
• Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products
  作者：Mudit Mudit、Mohammad Khanfar、Anbalagan Muralidharan、Shibu Thomas、Girish V. Shah、Rob W.M. van Soest、Khalid A. El Sayed

  DOI：10.1016/j.bmc.2008.12.053

  日期：2009.2

  The Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1), (R)-5-(4-hydroxybenzyl) hydantoin (2), and (Z)-5-((6-bromo-1H-indol-3-yl)methylene)-hydantoin (3). The natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)hydantoin (4) showed potent in vitro anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT and spheroid disaggregation assays. PMHs 1 and 4 also showed significant anti-invasive activities in orthotopic xenograft and transgenic mice models. To study the effect of electronic and lipophilic parameters on the activity, a wide array of several substituted aldehydes possessing electron-withdrawing (+sigma), lipophilic (+pi), electron-donating (-sigma), and less lipophilic substituents (-pi) were used to synthesize several PMHs. Few des-phenylmethylenehydantoins and 2-thiohydanoins were also synthesized and the anti-invasive activities of all compounds were evaluated. Comparative molecular field analysis (CoMFA) was then used to study the 3D QSAR. Predictive 3D QSAR model with conventional r(2) and cross validated coefficient (q(2)) values up to 0.910 and 0.651 were established. In conclusion, PMH is a novel antimetastatic lead class with potential to control metastatic prostate cancer. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis, microbial transformation, and pharmacological evaluation of 4,5-dihydronaphtho[2,1-b]furan-2-ones and related analogues
  作者：Khalid A. El Sayed、Ahmed I. Foudah、Alejandro M. S. Mayer、A. Michael Crider、Daniel Song

  DOI：10.1039/c3md00111c

  日期：——

  Reaction of 5- or 7-methoxy-2-tetralone with an α-bromoester using lithium diisopropylamide as the base gave tricyclic naphtho[2,1-b]furan-2-ones in one step. Catalytic reduction, epimerization with triethylamine and microbial transformations yielded several related analogues. Some naphtho[2,1-b]furan-2-ones showed anti-inflammatory and breast cancer migration inhibitory activities.

  以二异丙基酰胺锂为碱，将 5 或 7-甲氧基-2-四氢萘酮与 α-溴酯反应，一步即可得到三环萘并[2,1-b]呋喃-2-酮。通过催化还原、与三乙胺的环化反应以及微生物转化，得到了几种相关的类似物。一些萘并[2,1-b]呋喃-2-酮具有抗炎和抑制乳腺癌迁移的活性。