(Z)-5-(4-bromobenzylidene)imidazolidine-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: (Z)-5-(4-bromobenzylidene)imidazolidine-2,4-dione
• 英文别名: 5-(4-Bromobenzylidene)imidazolidine-2,4-dione；(5Z)-5-(4-bromobenzylidene)imidazolidine-2,4-dione；(5Z)-5-[(4-bromophenyl)methylidene]imidazolidine-2,4-dione
• 化学式: C₁₀H₇BrN₂O₂
• 分子量: 267.082
• InChiKey: CNYDLUVFKSOJMY-YVMONPNESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  58.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (Z)-5-(4-bromobenzylidene)imidazolidine-2,4-dione 在 三苯基膦 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 (5Z)-5-[(4-bromophenyl)methylidene]-3-[2-hydroxy-3-(propan-2-ylamino)propyl]imidazolidine-2,4-dione
  参考文献：
  名称：

  Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin

  摘要：

  A series of amine-alkyl derivatives of 5-arylidenehydantoin 3-21 was evaluated for their ability to improve antibiotic effectiveness in two strains of Gram-negative Enterobacter aerogenes: the reference strain (ATCC-13048) and the chloramphenicol-resistant derivative over-producing the AcrAB-TolC efflux pump (CM-64). Three antibiotics, chloramphenicol, nalidixic acid and sparfloxacin were used as markers of efflux pump activity. New compounds (5-16) were obtained within 3-4 step synthesis using Knoevenagel condensation, Mitsunobu reaction and microwave aided N-alkylation. Molecular modeling based structure-activity relationship (SAR) studies were performed. The most active compounds: (Z)-5-(4-(diethylamino) benzylidene)-3-(2-hydroxy-3-(4-(2-hydroxyethyl)piperazin-1-yl)propyl)imidazolidine-2,4-dione (14) and (Z)-5-(2,4-dimethoxybenzylidene)-3-(2-hydroxy-3-(isopropylamino)propyl)imidazolidine-2,4-dione (15) induced fourfold decrease of minimal inhibition concentration (MIC) of all tested antibiotics in the strain CM-64 overexpressing the AcrAB-TolC pump. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.10.053
• 作为产物：
  描述：

  海因 、 对溴苯甲醛 在 sodium acetate 作用下， 以 溶剂黄146 为溶剂， 反应 5.0h， 以50%的产率得到(Z)-5-(4-bromobenzylidene)imidazolidine-2,4-dione
  参考文献：
  名称：

  取代的咪唑烷二酮和硫代氧杂咪唑烷酮的合成及其抗菌活性。

  摘要：

  描述了新的3-苄基-4-硫代-5-芳基亚氨基咪唑烷-2-酮和3-苄基-5-芳基亚甲基咪唑烷-2,4-二酮的合成及其理化性质。这些化合物由芳族醛与3-取代的咪唑烷-2,4-二酮或4-硫代氧杂咪唑烷-2-酮缩合反应合成。5-亚苄基亚咪唑烷-2，4-二酮的N-烷基化同时导致单和二烷基化的衍生物。1-甲基-3-苄基咪唑烷-2，4-二酮与2-氰基-3-（3，4-二氯苯基）丙烯酸酯的亲核加成反应也产生了3-取代的5-芳基亚咪唑烷-2，4-二酮衍生物。对某些化合物测定了体外抗菌活性。

  DOI：

  10.1016/s0014-827x(98)00105-0

文献信息

• Synthesis and antimicrobial activity of substituted imidazolidinediones and thioxoimidazolidinones
  作者：J.F.C Albuquerque、J.A Rocha Filho、S.S.F Brandao、M.C.A Lima、E.A Ximenes、S.L Galdino、I.R Pitta、J Chantegrel、M Perrissin、C Luu-Duc

  DOI：10.1016/s0014-827x(98)00105-0

  日期：1999.1

  Synthesis and physico-chemical properties of new 3-benzyl-4-thioxo-5-arylideneimidazolidine-2-ones and 3-benzyl-5-arylideneimidazolidine-2,4-dione are described. These compounds were synthesized by condensation reaction from aromatic aldehydes and 3-substituted imidazolidine-2,4-diones or 4-thioxoimidazolidine-2-ones. The N-alkylation of 5-benzylideneimidazolidine-2,4-dione led simultaneously to mono-

  描述了新的3-苄基-4-硫代-5-芳基亚氨基咪唑烷-2-酮和3-苄基-5-芳基亚甲基咪唑烷-2,4-二酮的合成及其理化性质。这些化合物由芳族醛与3-取代的咪唑烷-2,4-二酮或4-硫代氧杂咪唑烷-2-酮缩合反应合成。5-亚苄基亚咪唑烷-2，4-二酮的N-烷基化同时导致单和二烷基化的衍生物。1-甲基-3-苄基咪唑烷-2，4-二酮与2-氰基-3-（3，4-二氯苯基）丙烯酸酯的亲核加成反应也产生了3-取代的5-芳基亚咪唑烷-2，4-二酮衍生物。对某些化合物测定了体外抗菌活性。
• Discovery of (<i>Z</i>)-5-(4-Methoxybenzylidene)thiazolidine-2,4-dione, a Readily Available and Orally Active Glitazone for the Treatment of Concanavalin A-Induced Acute Liver Injury of BALB/c Mice
  作者：Youfu Luo、Liang Ma、Hao Zheng、Lijuan Chen、Rui Li、Chunmei He、Shengyong Yang、Xia Ye、Zhizhi Chen、Zicheng Li、Yan Gao、Jing Han、Gu He、Li Yang、Yuquan Wei

  DOI：10.1021/jm901183d

  日期：2010.1.14

  that oral administration of 2g, 2h, 4f, or 6h decreases, most significantly for 4f, the serum levels of alanine aminotransaminase (ALT) and asparate aminotransaminase (AST) in ConA-induced acute livery injury BALB/c mice. Histopathological evaluation liver sections confirmed 4f as a potent, orally active compound for hepatoprotective effects against ConA-induced acute liver injury in BALB/c mice.

  大量证据表明，单核细胞/巨噬细胞浸润与多种炎性疾病有关，包括急性肝损伤。单核细胞趋化蛋白1（MCP-1）在巨噬细胞募集过程中起着至关重要的作用。我们在此提出了一种小分子文库和一种可行的快速筛选方法，用于评估抑制MCP-1刺激的RAW264.7细胞趋化性的能力。合成和筛选了53个小分子，四种化合物（2g，2h，4f和6h）显示出抑制作用，IC 50值范围为0.72至20.47μM，使用化合物4f是最有效的。进一步的体内研究表明，口服2g，2h，4f或6h可降低ConA诱导的急性肝损伤BALB / c小鼠的丙氨酸氨基转氨酶（ALT）和天冬酰胺转氨酶（AST）的血清水平，尤其是在4f时。组织病理学评估肝脏切片证实4f是一种有效的口服活性化合物，具有抗ConA诱导的BALB / c小鼠急性肝损伤的肝保护作用。
• Synthesis of Tetracyclic Spirooxindolepyrrolidine-Engrafted Hydantoin Scaffolds: Crystallographic Analysis, Molecular Docking Studies and Evaluation of Their Antimicrobial, Anti-Inflammatory and Analgesic Activities
  作者：Amani Toumi、Faiza I.A. Abdella、Sarra Boudriga、Tahani Y. A. Alanazi、Asma K. Alshamari、Ahlam Abdulrahman Alrashdi、Amal Dbeibia、Khaled Hamden、Ismail Daoud、Michael Knorr、Jan-Lukas Kirchhoff、Carsten Strohmann

  DOI：10.3390/molecules28217443

  日期：——

  µg/mL). Compound 4e bearing a p-chlorophenyl group on the pyrrolidine ring exhibited the greatest antifungal potential toward Candida albicans and Candida krusei (MIC values of 23.43 µg/mL and 46.87 µg/mL, respectively) as compared to Amphotericin B (MIC = 31.25 and 62.50 µg/mL, respectively). The target compounds were also tested in vitro against the lipoxygenase-5 (LOX-5) enzyme. Compounds 4i and

  在持续寻找具有多谱治疗应用的新型潜在候选药物的过程中，通过靛红衍生物、2-苯基甘氨酸和多种亚芳基-咪唑烷-2,4-二酮（乙内酰脲）之间的区域选择性三组分反应，设计并合成了一系列新型螺吲哚。 。通过 X 射线衍射研究和 NMR 光谱法确定了建议的立体化学。筛选所得四环杂环化合物的体外和体内抗炎和镇痛活性及其体外抗菌效力。体外抗菌筛选表明，几种衍生物对不同目标微生物表现出显着的生长抑制作用。与参比药物四环素 (MIC = 500 µg/mL) 相比，所有测试化合物均表现出优异的抗藤黄微球菌菌株活性 (93.75 µg/mL ≤ MIC ≤ 375 µg/mL)。与两性霉素 B（MIC = 31.25 和 62.50）相比，吡咯烷环上带有对氯苯基的化合物 4e 对白色念珠菌和克柔念珠菌表现出最大的抗真菌潜力（MIC 值分别为 23.43 µg/mL 和 46.87 µg/mL）分别为 µg/mL）。目标化合物还针对脂氧合酶
• Anticonvulsant Activity of Phenylmethylenehydantoins:  A Structure−Activity Relationship Study
  作者：Jeyanthi Chinnappa Thenmozhiyal、Peter Tsun-Hon Wong、Wai-Keung Chui

  DOI：10.1021/jm030450c

  日期：2004.3.1

  Phenylmethylenehydantoins (PMHs) and their des-phenyl analogues were synthesized and evaluated for anticonvulsant activity using the maximal electroshock seizure (MES) assay. The phenyl rings of PMHs were substituted with a wide spectrum of groups, and the selection of substituents was guided by Craig's plot. Phenylmethylenehydantoins substituted with alkyl (2, 3, 5, 6, 12, 14), halogeno (35, 38, 41), trifluoromethyl (11), and alkoxyl (23) groups at the phenyl ring were found to exhibit good anticonvulsant activity with EDMES(2.5) ranging from 28 to 90 mg/kg. Substitution of polar groups such as -NO2, -CN, and -OH was found to be less active or inactive on PMHs. Replacement of the phenyl ring with heteroaromatic rings reduced or caused the loss of anticonvulsant activity. The study identified two PMHs, 14 (EDMES(2.5) = 28 +/- 2 mg/kg) and 12 (EDMES(2.5) = 39 4 mg/kg), to be the most active candidates of the series, which are comparable to phenytoin (55, EDMES(2.5) = 30 +/- 2 mg/kg) in their protection against seizure. Multivariate analysis performed on the whole series of 54 PMHs further supported the finding that the alkylated phenylmethylenehydantoins are the best acting compounds. The SAR model derived on the basis of 12 of the most active phenylmethylenehydantoins demonstrated good predicting ability (root-mean-square error of prediction (RMSEP) = 0.134; RMSEE = 0.057) and identified LUMO energy and the log P as critical parameters for their anticonvulsant activity.
• Synthesis and antitumor evaluation of novel cyclic arylsulfonylureas: ADME-T and pharmacophore prediction
  作者：Ibrahim M. El-Deeb、Said M. Bayoumi、Magda A. El-Sherbeny、Alaa A.-M. Abdel-Aziz

  DOI：10.1016/j.ejmech.2010.02.038

  日期：2010.6

  Novel derivatives of 5-(substituted)benzylidene-3-(4-substituted)phenylsulfonylimidazolidine-2,4-diones (3a-r), 1-(4-substituted)phenylsulfonyl-3-(4-substituted)phenylpyrimidine-2,4,6-(1H,3H,5H)-triones (6a-l), and 3-(4-substituted)phenyl-1-(4-substituted)phenylsulfonylquinazoline-2,4(1H,3H)-diones (8a-l) have been synthesized and tested for their antitumor activity against 60 tumor cell lines taken from 9 different organs. The tested compounds have showed good inhibitory effect at the ovarian cancer (IGROV1) cell line. A significant inhibition for (RXF393) renal cancer cells was observed with series 3 compounds, while in the other two series 6 and 8, there was a significant inhibition of ovarian cancer cells (OVCAR-8) and melanoma cells (SK-MEL-2). Interestingly, beside the strong inhibition of compound 3q to IGROV1 and RXF393 cells, a great inhibition (199 62%) for (M14) Melanoma cells was observed at the tested concentration (10 mu M) ADME-T and pharmacophore prediction methodology were used to study the antitumor activity of the most active compounds and to identify the structural features required for antitumor activity.