methyl 2-(3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate | 1350707-12-8

• 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: methyl 2-(3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate
• 英文别名: methyl 2-(2,4-dioxo-5,5-diphenyl-1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)imidazolidin-3-yl)acetate；Methyl 2-[3-[4-[4-(2-methoxyphenyl)piperazin-1-yl]butyl]-2,5-dioxo-4,4-diphenylimidazolidin-1-yl]acetate
• CAS: 1350707-12-8
• 化学式: C₃₃H₃₈N₄O₅
• 分子量: 570.689
• InChiKey: LUIJLIIDIVJXQI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  42
• 可旋转键数：
  12
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  82.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate 在 盐酸 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 为溶剂， 反应 2.0h， 生成 2-(3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetic acid hydrochloride
  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：

  methyl 2-(2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate 在 苄基三乙基氯化铵 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 121.0h， 生成 methyl 2-(3-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate
  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

• 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.
• Amine–alkyl derivatives of hydantoin: New tool to combat resistant bacteria
  作者：Jadwiga Handzlik、Ewa Szymańska、Jacqueline Chevalier、Ewa Otrębska、Katarzyna Kieć-Kononowicz、Jean-Marie Pagès、Sandrine Alibert

  DOI：10.1016/j.ejmech.2011.09.032

  日期：2011.12

  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.