3-methyl-1-(oxiran-2-ylmethyl)-5,5-diphenylimidazolidine-2,4-dione | 1041926-38-8

• 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: 3-methyl-1-(oxiran-2-ylmethyl)-5,5-diphenylimidazolidine-2,4-dione
• CAS: 1041926-38-8
• 化学式: C₁₉H₁₈N₂O₃
• 分子量: 322.364
• InChiKey: QMWPSOJVACEAHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  24.0
• 可旋转键数：
  4.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  53.15
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-methyl-1-(oxiran-2-ylmethyl)-5,5-diphenylimidazolidine-2,4-dione 在 盐酸 作用下， 以 甲醇 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：

  3-甲基-5,5-二苯基海因 、 环氧氯丙烷 在 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 3-methyl-1-(oxiran-2-ylmethyl)-5,5-diphenylimidazolidine-2,4-dione
  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

文献信息

• Synthesis, α1-adrenoceptor antagonist activity, and SAR study of novel arylpiperazine derivatives of phenytoin
  作者：Jadwiga Handzlik、Dorota Maciąg、Monika Kubacka、Szczepan Mogilski、Barbara Filipek、Katarzyna Stadnicka、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2008.04.058

  日期：2008.6

  In the search for new antiarrhythmic agents, some active 2-methoxyphenylpiperazine derivatives of phenytoin were obtained as a chemical modification of compound AZ-99 (3-ethyl-1-[2-hydroxy-3-(4-phenylpiperazin-1-yl)-propyl]-2,4-dioxo-5,5-diphenylim idazolidine). These compounds possessed structural properties similar to those of alpha(1)-adrenoceptor antagonists. In the present study, the affinities

  在寻找新的抗心律失常药时，苯妥英钠的一些活性2-甲氧基苯基哌嗪衍生物作为化合物AZ-99（3-乙基-1- [2-羟基-3-（4-苯基哌嗪-1-基） -丙基] -2,4-二氧代-5,5-二苯基咪唑烷）。这些化合物具有与α（1）-肾上腺素受体拮抗剂相似的结构性质。在本研究中，使用放射性配体（[（3）H] prazosin，[（3）H]对2-甲氧基苯基哌嗪衍生物（1a-3a）对α（1）-和α（2）-肾上腺素受体的亲和力进行了评估可乐定）结合测定。下一步，是苯妥英钠（4a-16a）的一系列新的苯基哌嗪衍生物，在2处含有2-甲氧基苯基，2-乙氧基苯基，2-吡啶基或2-呋喃基哌嗪部分，以及各种酯或烷基取代基合成乙内酰脲环的-位。测试了新合成的化合物对α（1）-和α（2）-肾上腺素受体的亲和力。他们显示了在纳摩尔至亚微摩尔范围内的α（1）-肾上腺素受体的亲和力。一些化合物是α（1）-肾上腺素受体的中等选
• Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α1-adrenoceptor affinities
  作者：Jadwiga Handzlik、Marek Bajda、Małgorzata Zygmunt、Dorota Maciąg、Małgorzata Dybała、Marek Bednarski、Barbara Filipek、Barbara Malawska、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2012.02.009

  日期：2012.4

  An association between alpha(1)-adrenoceptor affinities, hERG K+-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a-21a) was investigated. New compounds were synthesized and tested for their affinity for alpha(1)-adrenoceptors in radioligand binding assay using [H-3]-prazosin as a selective radioligand. Antiarrhythmic activities in adrenaline-and barium chloride-induced arrhythmia models, an influence of the phenylpiperazine derivatives on the ECG-components and blood pressure were tested in vivo in normotensive rats. The hERG K+-antagonistic properties of the most potent antiarrhythmic agents were investigated in silico by the use of program QikProp. The highest alpha(1)-adrenoceptor affinity (K-i = 4.7 nM) and the strongest antiarrhythmic activity in adrenaline induced arrhythmia (ED50 = 0.1 mg/kg) was found for 1-(4-(4-(2-methoxyphenyl)piperazin-1-yl) butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione hydrochloride (19a). The results indicated a significant correlation between alpha(1)-AR affinities (pK(i)) and antiarrhythmic activity (ED50) in adrenaline model (R-2 = 0.92, p < 0.005). Influence of the examined phenylpiperazine hydantoin derivatives on hERG K+ channel, predicted by means of in silico methods, suggested their hERG K+-blocking properties. (C) 2012 Elsevier Ltd. All rights reserved.