3-甲基-5,5-二苯基海因 | 4224-00-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 中文名称: 3-甲基-5,5-二苯基海因
• 英文名称: 3-methyl-5,5-diphenyl-imidazolidine-2,4-dione
• 英文别名: 3-methyl-5,5-diphenylhydantoin；monomethylphenytoin；3-Methyl-5,5-diphenyl-imidazolidin-2,4-dion；5,5-diphenyl-3-methyl-tetrahydro-imidazole-2,4-dione；3-Methyl-5,5-diphenylimidazolidine-2,4-dione
• CAS: 4224-00-4
• 化学式: C₁₆H₁₄N₂O₂
• 分子量: 266.299
• InChiKey: LTYDTBHSPIJPEG-UHFFFAOYSA-N

物化性质

• 熔点：
  216-217 °C
• 密度：
  1.235±0.06 g/cm3(Predicted)
• 保留指数：
  2299;2350.3

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  49.4
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  3-甲基-5,5-二苯基海因 在 盐酸 、 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 甲醇 、 丙酮 为溶剂， 反应 48.25h， 生成 1-(3-methyl-2,4-dioxo-5,5-diphenylimidazolidin-1-yl)-3-(4-phenylpiperazin-1-yl)propan-2-yl acetate dihydrochloride
  参考文献：
  名称：

  Amine–alkyl derivatives of hydantoin: New tool to combat resistant bacteria

  摘要：

  A series of new 5,5-diphenylhydantoin derivatives with various amine alkyl terminal fragments at N1-position were synthesized. Then a series of twenty-eight compounds with the same hydantoin scaffold were evaluated for their potency to combat bacterial MultiDrug Resistance (MDR). Intrinsic antibacterial activities were first evaluated. As these compounds showed no direct activity on bacteria, their influence on minimal inhibitory concentration (MIC) of nalidixic acid was tested in two strains of Enterobacter aerogenes: the reference-strain ATCC-13048 and the CM-64 strain which over-produces AcrAB-ToIC efflux pump. The compounds showed moderate- or low- anti-MDR properties. According to SAR-studies, hit compounds containing 2-methoxyphenylpiperazine at N1-terminal fragment and methylcarboxyl acid one at N3-position of hydantoin have been identified for further microbiological studies and pharma-comodulations to develop efflux pump inhibitors. (C) 2011 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2011.09.032
• 作为产物：
  描述：

  alkaline earth salt of/the/ methylsulfuric acid 在 alcoholic alkali 作用下， 生成 3-甲基-5,5-二苯基海因
  参考文献：
  名称：

  Biltz, Justus Liebigs Annalen der Chemie, 1909, vol. 368, p. 211

  摘要：

  DOI：

文献信息

• Structure-activity relationships of 3-substituted-5,5- diphenylhydantoins as potential antiproliferative and antimicrobial agents
  作者：Nemanja Trisovic、Bojan Bozic、Ana Obradovic、Olgica Stefanovic、Snezana Markovic、Ljiljana Comic、Biljana Bozic、Gordana Uscumlic

  DOI：10.2298/jsc110314143t

  日期：——

  A series of twelve 3-substituted-5,5-diphenylhydantoins was synthesized, including some whose anticonvulsant activities have already been reported in the literature. Their antiproliferative activities against HCT-116 human colon carcinoma cells were evaluated to determine structure-activity relationships. Almost all of the compounds exhibited statistically significant antiproliferative effects at a concentration of 100 ?M, while the derivative bearing a benzyl group was active even at lower concentrations. Moreover, their in vitro antibacterial activities against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923 and clinical isolates of Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, Enterococcus faecalis and Staphylococcus aureus were evaluated. Only the 3-iso-propyl and 3-benzyl derivatives showed weak antibacterial activities against the Gram-positive bacterium E. faecalis and the Gram-negative bacteria E. coli ATCC 25922 and E. coli.

  合成了十二种 3-取代-5,5-二苯基海因系列、 包括一些已在文献中报道过其抗惊厥活性的化合物。 文献中已有报道。评估了它们对 HCT-116 人结肠癌细胞的抗增殖活性，以确定其作用机制。 结肠癌细胞的抗增殖活性进行了评估，以确定结构-活性关系。 关系。几乎所有化合物都表现出了统计学意义上的 的抗增殖作用，而带有苄基的衍生物在浓度为 100? 而带有苄基的衍生物即使在较低浓度下也具有活性。 此外，它们在体外对大肠杆菌 大肠杆菌 ATCC 25922、金黄色葡萄球菌 ATCC 25923 和临床分离的 大肠杆菌、奇异变形杆菌、铜绿假单胞菌、粪肠球菌和葡萄球菌的体外抗菌活性。 粪肠球菌和金黄色葡萄球菌进行了评估。只有 3-异丙基和 3-苄基衍生物对革兰氏阳性菌大肠杆菌和金黄色葡萄球菌表现出微弱的抗菌活性。 革兰氏阳性菌粪肠球菌和革兰氏阴性菌大肠杆菌 ATCC 25922 和 E. coli.
• SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives
  作者：Jadwiga Handzlik、Andrzej J. Bojarski、Grzegorz Satała、Monika Kubacka、Bassem Sadek、Abrar Ashoor、Agata Siwek、Małgorzata Więcek、Katarzyna Kucwaj、Barbara Filipek、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.ejmech.2014.01.065

  日期：2014.5

  on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer–Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT7 and

  当前的研究集中在新开发的芳族甲基乙内酰脲的苯基哌嗪衍生物，其甲基和苯基部分的相互位置不同。这些新化合物是通过Bucherer-Bergs反应，两相烷基化，Mitsunobu反应和/或微波辐射下的烷基化反应合成的。开发的化合物在其亲和力被评定为血清素受体5-HT 1A，5-HT 6，5-HT 7，α 1个在放射性配体结合测定-ARs。选择的化合物在人类上的抑制作用测试5-HT 3A中所表示的爪蟾卵母细胞，以及对它们的活性在α 1-肾上腺素受体亚型分别在功能和电生理生物测定中。研究最多的化合物均显示出亲和力α 1 -ARs，5-HT 1A，5-HT 7（ķ我 〜0.8-353 nm）的比对5-HT显著更高6个受体。在5-HT非常弱的抑制效果3A在α伴随着高活性1D，观察选择的代表性化合物-AR亚型。在当前系列中，特别是5-（4-氟苯基）-3-（2-羟基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙基）-5-甲基咪唑烷-2
• Chitosan decorated Fe₃O₄nanoparticles as a magnetic catalyst in the synthesis of phenytoin derivatives
  作者：Javad Safari、Leila Javadian

  DOI：10.1039/c4ra06618a

  日期：——

  In the present work, Fe3O4 nanoparticles were synthesized by the chemical coprecipitation process. Subsequently, the synthesized nanoparticles were modified with chitosan by a simple method and characterized by X-ray diffractometry (XRD), Fourier transform infrared spectrophotometry (FT-IR), vibrating sample magnetometry (VSM), scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). Then, phenytoin derivatives were catalyzed by magnetic Fe3O4–chitosan nanoparticles. Fe3O4–chitosan nanoparticles were found to be a recoverable organocatalyst for the efficient synthesis of 5,5-diphenylhydantoins and 5,5-diphenyl-2-thiohydantoins from substituted benzils and urea or thiourea derivatives. The nanocatalyst could be recovered easily under a magnetic field for reuse, and considerable loss of its catalytic activity was not observed after reuse in seven consecutive runs.

  本研究采用化学共沉淀法合成了 Fe3O4 纳米粒子。随后，用简单的方法对合成的纳米粒子进行壳聚糖修饰，并通过 X 射线衍射仪（XRD）、傅立叶变换红外分光光度法（FT-IR）、振动样品磁力计（VSM）、扫描电子显微镜（SEM）和能量色散 X 射线光谱（EDX）对其进行表征。然后，用磁性 Fe3O4 壳聚糖纳米颗粒催化苯妥英衍生物。研究发现，Fe3O4-壳聚糖纳米颗粒是一种可回收的有机催化剂，可从取代的苯并芘和脲或硫脲衍生物中高效合成 5,5-二苯基海因和 5,5-二苯基-2-硫代海因。该纳米催化剂可在磁场下轻松回收再利用，连续七次重复使用后也未发现其催化活性有明显下降。
• New aspects of reactions of methyl (thio)ureas with benzil
  作者：Vladimir V. Baranov、Tatyana N. Vol'khina、Yulia V. Nelyubina、Angelina N. Kravchenko

  DOI：10.1016/j.mencom.2021.09.027

  日期：2021.9

  New pathways of reaction between 1-methylthiourea or 1-methylurea and benzil bring about new derivatives of (2S*,3aR*,6aS*)-perhydro-3aH-[1,3]dioxolo[4,5-d]imidazole and racemic (4S*,5R*)-4-alkoxy-5-hydroxy-1-methyl-4,5-diphenylimidazolidine-2-thiones. Some of the obtained urea-and thiourea derivatives were characterized by X-ray diffraction, which showed their supramolecular organization governed

  1-甲基硫脲或1-甲基脲与苄基反应的新途径产生(2 S *,3a R *,6a S *)-perhydro-3a H -[1,3]dioxolo[4,5- d的新衍生物]咪唑和外消旋 (4 S *,5 R *)-4-烷氧基-5-羟基-1-甲基-4,5-二苯基咪唑烷-2-硫酮。一些获得的脲和硫脲衍生物通过 X 射线衍射表征，表明它们的超分子组织受受体侧 C=O 或 C=S 基团的氢键方向性控制。
• Direct <i>N</i><sup>1</sup>-Selective Alkylation of Hydantoins Using Potassium Bases
  作者：Yumi Shintani、Koichi Kato、Masashi Kawami、Mikihisa Takano、Takuya Kumamoto

  DOI：10.1248/cpb.c20-00857

  日期：2021.4.1

  potassium hexamethyldisilazide (KHMDS)] in tetrahydrofuran (THF) gave N1-monomethylated phenytoin in good yield. The applicable scope of this reaction system was found to include various hydantoins and alkyl halides. To explore the function of methylated hydantoins, the effects of a series of methylated phenytoins on P-glycoprotein were examined, but none of methylated products showed inhibitory activity

  乙内酰脲，包括抗癫痫药苯妥英钠，含有酰胺氮和酰亚胺氮，两者均可被烷基化。然而，由于其质子的较高酸度，在碱性条件下，N 3比N 1更容易烷基化。在这项研究中，我们探索了苯妥英钠直接N 1-选择性甲基化的方法，并发现在四氢呋喃（THF）中使用钾碱[叔丁醇钾（t BuOK）和六甲基二硅叠氮化钾（KHMDS）]产生的条件得到N 1-单甲基化苯妥英钠收率好。发现该反应系统的适用范围包括各种乙内酰脲和烷基卤。为了探索甲基化乙内酰脲的功能，研究了一系列甲基化苯妥英对P-糖蛋白的作用，但没有一种甲基化产物对P-糖蛋白对罗丹明123流出具有抑制活性。 全尺寸图片