3-(2-(4-fluorophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione

• 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-(2-(4-fluorophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione
• 英文别名: 3-[2-(4-Fluorophenyl)-2-oxoethyl]-5,5-diphenylimidazolidine-2,4-dione
• 化学式: C₂₃H₁₇FN₂O₃
• 分子量: 388.398
• InChiKey: CUQSBYJYIVHHFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  29.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  66.48
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(2-乙氧基苯基)哌嗪 、 3-(2-(4-fluorophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 6.0h， 以55%的产率得到3-(2-(4-(4-(2-ethoxyphenyl)piperazin-1-yl)phenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione
  参考文献：
  名称：

  Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives

  摘要：

  Series of 3-alkyl, 3-aryl-5,5-diphenylimidazolidine-2,4-diones (2-8) and 3-phenacyl-5,5-diphenylimidazolidine-2,4-diones (9-20) were designed, synthesized, and tested for their antitumor activity. The 13 compounds (3-8, 10-15 and 20) were selected by National Cancer Institute (USA) on the basis of degree of the structure variation and computer modeling techniques for evaluation of their antineoplastic activity. A single dose (10 mu M) of the tested compounds was used in the National Cancer Institute (NCI) 60 cell lines panel assay selected from different nine organs. The tested compounds possessed selective activity against the renal cancer (A498 and UO-31) cell lines. Interestingly, compound 13 showed moderate selective activities towards A498 and UO-31 cell lines, in addition to strong activity against melanoma (MDA-MB-435) cell line and breast cancer cell lines (MCF7) in 114 and 70 %, respectively. Molecular docking study was performed for the most active compound 13 to identify the structural features required for the antitumor activity. The results achieved can be used as a useful template for future development and further derivatization or modification to obtain more potent and selective antitumor agents.The development of novel molecules containing imidazolidine-2,4-dione pharmacophore have shown promising antitumor activities. Compound 13 exploited broad spectrum and potent antitumor activity with the percentages of inhibition range of 28-114 %.

  DOI：

  10.1007/s00044-013-0597-1
• 作为产物：
  描述：

  苯妥英 、 2-氯代-4'-氟苯乙酮 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 24.0h， 生成 3-(2-(4-fluorophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione
  参考文献：
  名称：

  基于5,5-二苯基咪唑烷-2,4-二酮骨架的苯甲酸酯的合成，抗炎，镇痛和COX-1 / 2抑制活性：分子对接研究。

  摘要：

  报道了一组5,5-二苯基咪唑烷-2,4-二酮带有苯胺，苯甲酰基和亚苄基片段2-27的设计，合成和药理活性。体内评估了制备的5,5-二苯基咪唑烷-2,4-二酮衍生物的抗炎，镇痛活性，体外评估了COX-1 / 2抑制作用。在所测试的化合物中，衍生物5、9、10、13和14表现出显着和有效的抗炎和镇痛活性，几乎等同于参考药物塞来昔布。在COX-1 / 2抑制试验中，化合物5、9、10和14表现出较高的COX-2抑制活性（IC50分别为0.70μM，0.44μM，0.61μM和0.41μM），选择性指数（SI）范围为142 -243可比塞来昔布[COX-2（SI）> 333]。这些有效的COX-2抑制剂9、10、13

  DOI：

  10.1016/j.ejmech.2016.03.011

文献信息

• Synthesis, anti-inflammatory, analgesic and COX-1/2 inhibition activities of anilides based on 5,5-diphenylimidazolidine-2,4-dione scaffold: Molecular docking studies
  作者：Alaa A.-M. Abdel-Aziz、Adel S. El-Azab、Laila A. Abou-Zeid、Kamal Eldin H. ElTahir、Naglaa I. Abdel-Aziz、Rezk R. Ayyad、Abdulrahman M. Al-Obaid

  DOI：10.1016/j.ejmech.2016.03.011

  日期：2016.6

  The design, synthesis and pharmacological activities of a group of 5,5-diphenylimidazolidine-2,4-dione bearing anilide, phenacyl and benzylidene fragments 2-27 were reported. The prepared 5,5-diphenylimidazolidine-2,4-dione derivatives were evaluated in vivo for anti-inflammatory, analgesic activities and in vitro for COX-1/2 inhibition assay. Among the tested compounds, derivatives 5, 9, 10, 13, and

  报道了一组5,5-二苯基咪唑烷-2,4-二酮带有苯胺，苯甲酰基和亚苄基片段2-27的设计，合成和药理活性。体内评估了制备的5,5-二苯基咪唑烷-2,4-二酮衍生物的抗炎，镇痛活性，体外评估了COX-1 / 2抑制作用。在所测试的化合物中，衍生物5、9、10、13和14表现出显着和有效的抗炎和镇痛活性，几乎等同于参考药物塞来昔布。在COX-1 / 2抑制试验中，化合物5、9、10和14表现出较高的COX-2抑制活性（IC50分别为0.70μM，0.44μM，0.61μM和0.41μM），选择性指数（SI）范围为142 -243可比塞来昔布[COX-2（SI）> 333]。这些有效的COX-2抑制剂9、10、13
• Crystal, molecular structure, and conformational preferences of 3-(2-(4-morpholinophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione
  作者：Alaa A.-M. Abdel-Aziz、Hazem A. Ghabbour、Adel S. El-Azab、Nasr Y. Khalil、Hoong-Kun Fun、Magda A. El-Sherbeny

  DOI：10.1080/15421406.2016.1149027

  日期：2016.5.23

  The X-ray crystal structure of 3-(2-(4-morpholinophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione (2) [C27H25N3O4: MF = 455.50, monoclinic, P21/c, a = 6.2038 (2) Å, b = 20.8905 (6) Å, c = 18.3361 (6) Å, b = 97.594 (2)ο, V = 2355.53 Å3, Z = 4, Dcalc = 1.284 Mg m−3, λ = 1.54178 Å] was determined. The crystal packing confirmed the occurrence of two conformers of opposite conformation. Conformational

  摘要 3-(2-(4-morpholinophenyl)-2-oxoethyl)-5,5-diphenylimidazolidine-2,4-dione (2) [C27H25N3O4: MF = 455.50, 单斜晶系, P21/c 的 X 射线晶体结构, a = 6.2038 (2) Å, b = 20.8905 (6) Å, c = 18.3361 (6) Å, b = 97.594 (2)ο, V = 2355.53 Å3, Z = 4, Dcalc = 1.284 Mg m−3, λ = 1.54178 Å] 已确定。晶体堆积证实了两种相反构象的构象异构体的出现。化合物2的构象方面指出了决定所研究系统构象的两个因素：第一，晶体堆积的分子间氢键，稳定并有利于两个独立分子的出现，第二个因素是空间位阻取代基之间。
• Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives
  作者：Amer M. Alanazi、Adel S. El-Azab、Ibrahim A. Al-Swaidan、Azza R. Maarouf、Eman R. El-Bendary、Mohamed A. Abu El-Enin、Alaa A.-M. Abdel-Aziz

  DOI：10.1007/s00044-013-0597-1

  日期：2013.12

  Series of 3-alkyl, 3-aryl-5,5-diphenylimidazolidine-2,4-diones (2-8) and 3-phenacyl-5,5-diphenylimidazolidine-2,4-diones (9-20) were designed, synthesized, and tested for their antitumor activity. The 13 compounds (3-8, 10-15 and 20) were selected by National Cancer Institute (USA) on the basis of degree of the structure variation and computer modeling techniques for evaluation of their antineoplastic activity. A single dose (10 mu M) of the tested compounds was used in the National Cancer Institute (NCI) 60 cell lines panel assay selected from different nine organs. The tested compounds possessed selective activity against the renal cancer (A498 and UO-31) cell lines. Interestingly, compound 13 showed moderate selective activities towards A498 and UO-31 cell lines, in addition to strong activity against melanoma (MDA-MB-435) cell line and breast cancer cell lines (MCF7) in 114 and 70 %, respectively. Molecular docking study was performed for the most active compound 13 to identify the structural features required for the antitumor activity. The results achieved can be used as a useful template for future development and further derivatization or modification to obtain more potent and selective antitumor agents.The development of novel molecules containing imidazolidine-2,4-dione pharmacophore have shown promising antitumor activities. Compound 13 exploited broad spectrum and potent antitumor activity with the percentages of inhibition range of 28-114 %.
• Synthesis, structural characterization, DFT calculations and antiproliferative evaluation of novel spirohydantoin derivatives containing a substituted benzyl moiety
  作者：Anita M. Lazić、Lidija D. Radovanović、Bojan Đ. Božić、Biljana Đ. Božić Nedeljković、Vesna D. Vitnik、Željko J. Vitnik、Jelena R. Rogan、Nataša V. Valentić、Gordana S. Ušćumlić、Nemanja P. Trišović

  DOI：10.1016/j.molstruc.2018.11.071

  日期：2019.3

  of Lipinski demonstrated that all investigated compounds obeyed the rule of five. To further understand their geometry and electronic structure, DFT calculations with B3LYP method using 6-311++G(d,p) basic set were performed. In this context, the UV–Vis spectra of the investigated compounds were analyzed in detail, whereby the predicted absorption spectra from DFT calculation matched the experimentally

  摘要 合成了两个系列的环烷螺-5-乙内酰脲，即环己烷螺-5-乙内酰脲和环庚烷螺-5-乙内酰脲在N3位具有4-取代的苄基或2-(4-取代的苯基)-2-氧乙基，并测试了它们对人结肠 (HCT-116)、白血病 (K562) 和乳腺癌 (MDA-MB-231) 癌细胞系增殖的影响。为了进行比较，我们还描述了 5,5-二苯基乙内酰脲类似物。所研究化合物的结构特征通过元素分析、FT-IR、UV-Vis、1H 和 13C NMR 光谱和 X 射线晶体学进行表征。关于它们的结构-活性关系，表明苄基部分被甲氧基、氯或溴基团取代增强了相对于母体化合物的抗增殖活性，而环烷基大小的增加主要导致抗增殖活性的降低。单晶X射线分析显示存在由NH⋯O氢键形成的二聚体和链。Lipinski 的分子描述符分析表明，所有研究的化合物都遵循五法则。为了进一步了解它们的几何形状和电子结构，使用 B3LYP 方法使用 6-311++G(d