methyl 2-(3-(4-bromobutyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate | 1350706-97-6

• 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: methyl 2-(3-(4-bromobutyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate
• 英文别名: Methyl 2-[3-(4-bromobutyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl]acetate
• CAS: 1350706-97-6
• 化学式: C₂₂H₂₃BrN₂O₄
• 分子量: 459.34
• InChiKey: DFJQOYUSGJYCQU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  66.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-(4-bromobutyl)-2,5-dioxo-4,4-diphenylimidazolidin-1-yl)acetate 在 盐酸 、 苄基三乙基氯化铵 、 potassium carbonate 、 potassium hydroxide 作用下， 以 甲醇 、 乙醇 、 水 、 丙酮 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：

  1,4-二溴丁烷 、 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， 以88%的产率得到methyl 2-(3-(4-bromobutyl)-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

• Discovery of phenylselenoether-hydantoin hybrids as ABCB1 efflux pump modulating agents with cytotoxic and antiproliferative actions in resistant T-lymphoma
  作者：Wesam Ali、Gabriella Spengler、Annamária Kincses、Márta Nové、Cecilia Battistelli、Gniewomir Latacz、Małgorzata Starek、Monika Dąbrowska、Ewelina Honkisz-Orzechowska、Annalisa Romanelli、Manuela Monica Rasile、Ewa Szymańska、Claus Jacob、Clemens Zwergel、Jadwiga Handzlik

  DOI：10.1016/j.ejmech.2020.112435

  日期：2020.8

  terms of design, synthesis, and biological assays, including an insight into cellular mechanisms of anticancer action as well as an ADMET-screening in vitro were performed, followed by in-depth SAR analysis. Among the investigated new phenylselenoether hybrids, four compounds showed significant cytotoxic and anti-proliferative effects, in particular, in resistant cancer cells. Hydantoin derivatives (5–7)

  癌细胞中的多药耐药性（MDR）是成功治疗癌症要考虑的关键方面。P-gp / ABCB1是ABC转运蛋白的成员，参与了主要的肿瘤MDR机制，负责药物和细胞毒性物质的外排。在这里，我们描述了一种具有潜在抗癌活性的有效的含硒ABCB1 MDR外排泵调节剂的发现。对三组硒醚进行了设计，合成和生物学分析方面的全面研究，包括深入了解抗癌作用的细胞机制以及体外ADMET筛选进行了深入的SAR分析。在研究的新的苯基硒醚杂化物中，四种化合物表现出显着的细胞毒性和抗增殖作用，特别是在耐药性癌细胞中。乙内酰脲衍生物（5 – 7）比参考抑制剂维拉帕米（在低10倍的浓度下最高可达2.6倍）调节ABCB1外排泵的效果显着，并且还具有良好的药物相互作用曲线。最好的化合物（6在人的JURKAT T淋巴细胞癌细胞中进一步评估了其对细胞增殖速率的影响。从机制上讲，细胞周期增强剂cyclin D1的表达下降，而单独用化合物6或
• 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.