(5Z)-5-(4-(dimethylamino)benzylidene)imidazolidine-2,4-dione | 10040-87-6

• 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: (5Z)-5-(4-(dimethylamino)benzylidene)imidazolidine-2,4-dione
• 英文别名: (Z)-5-(4-dimethylaminobenzylidene)imidazolidine-2,4-dione；(Z)-5-(4-dimethylaminobenzylidene)hydantoin；5-(4-Dimethylamino-benzylidene)-imidazolidine-2,4-dione；(5Z)-5-[[4-(dimethylamino)phenyl]methylidene]imidazolidine-2,4-dione
• CAS: 10040-87-6；137920-43-5；137920-44-6
• 化学式: C₁₂H₁₃N₃O₂
• 分子量: 231.254
• InChiKey: KLVRHZIOWMWJOC-YFHOEESVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  61.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (5Z)-5-(4-(dimethylamino)benzylidene)imidazolidine-2,4-dione 在 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (Z)-5-(4-(dimethylamino)benzylidene)-3-(3-(4-(2-ethoxyphenyl)piperazin-1-yl)-2-hydroxypropyl)imidazolidine-2,4-dione
  参考文献：
  名称：

  合成和SAR-研究5-arylidenehydantoin的芳基哌嗪新颖衍生物与α 1肾上腺素能受体拮抗性质

  摘要：

  该研究集中在一系列5-乙叉基乙内酰脲衍生物上，该衍生物在乙内酰脲环的N3处有一个苯基哌嗪-羟丙基片段。这些化合物进行了评估他们对α亲和力1 -肾上腺素受体和它们的拮抗性质官能生物测定法进行评价。（Z）-5-（4-氯亚苄基）-3-（3-（4-（2-乙氧基苯基）哌嗪-1-基）-2-羟丙基）咪唑烷-2,4-二酮的晶体结构（7）和（Z）-5-（4-氯亚苄基）-3-（2-羟基-3-（4-（2-甲氧基苯基）哌嗪-1-基）丙基）咪唑烷-2,4-二酮的盐酸盐（10a使用X射线衍射法求解。经典的分子力学（MMFFs力场，MCMM，MacroModel）被用于使用7的晶体结构预测化合物5a – 18a的3D结构。被巴尔巴罗的药效团模型和先前研究α结构特性的基础上执行SAR分析1具有乙内酰脲片段-肾上腺素受体拮抗剂。大多数化合物表现出显著亲和力α 1个在纳摩尔范围内（40-290纳米）-ARs。最高活动（K i

  DOI：

  10.1016/j.bmc.2012.05.064
• 作为产物：
  描述：

  5-(4-二甲基氨基-苄亚基)-2-硫代-咪唑烷-4-酮 在 盐酸 、 乙醇 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 (5Z)-5-(4-(dimethylamino)benzylidene)imidazolidine-2,4-dione
  参考文献：
  名称：

  作为潜在抗病毒剂的 5-亚芳基-2-乙内酰脲的合成、反应和构象分析

  摘要：

  摘要 (Z)-5-Arylidene-1-(4-methylphenylsulfonyl)-2-thiohydantoins 5a,b 由芳香醛 4a,b 与 1-(4-methylphenylsulfonyl)-2-thiohydantoins 3a 直接缩合合成，湾 化合物 5a,b 在碱性条件下与 2'-脱氧-3',5'-二(4-甲基-苯甲酰基)-α-D-赤型-戊呋喃酰氯 6 偶联得到 N3 保护的核苷 7a,b。5a,b 与氯甲基甲硫醚和/或2-溴乙醛二乙缩醛在碱性介质中反应得到N3-烷基衍生物8a-c。5a 与 1,2-二氯乙烷在碱性条件下反应得到双硫代乙内酰乙烷 9a,b。化合物5a、b与甲醛和仲胺缩合，得到3-氨基甲基-2-硫代乙内酰脲衍生物10a-d。另一方面，未取代的 2-硫代乙内酰脲衍生物 11b 的反应，c 与氯甲基甲基硫醚分别得到单甲硫基和双甲硫基衍生物 12a,b

  DOI：

  10.1080/10426500108040603

文献信息

• Privileged Scaffolds or Promiscuous Binders: A Comparative Study on Rhodanines and Related Heterocycles in Medicinal Chemistry
  作者：Thomas Mendgen、Christian Steuer、Christian D. Klein

  DOI：10.1021/jm201243p

  日期：2012.1.26

  campaigns, we decided to perform a systematic study on their promiscuity. An amount of 163 rhodanines, hydantoins, thiohydantoins, and thiazolidinediones were synthesized and tested against several targets. The compounds were also characterized with respect to aggregation and electrophilic reactivity, and the binding modes of rhodanines and related compounds in published X-ray cocrystal structures were analyzed

  罗丹宁和具有多个杂原子的相关五元杂环最近因在筛选活动中表现为“频繁的杀手”而成为非选择性化合物，因此在药物发现中几乎没有价值。但是，这种判断似乎主要是基于轶事证据。在筛选活动中鉴定出多种罗丹宁和相关化合物后，我们决定对它们的滥交进行系统的研究。合成了163种罗丹宁，乙内酰脲，硫代乙内酰脲和噻唑烷二酮，并针对几个目标进行了测试。还针对聚集和亲电反应性对化合物进行了表征，并分析了罗丹宁与相关化合物在已发表的X射线共晶结构中的结合模式。结果表明，环外，若丹宁和硫代乙内酰脲中的双键硫原子除具有其他结构特征外，还为极性相互作用和氢键提供了特别高的相互作用位点密度。这会导致“筛选范围”内浓度的混杂行为，但不应视为将此类筛选命中排除在进一步开发之外的一般剔除标准。建议将针对靶标亲和力和选择性的特殊标准应用于这些类型的化合物，并因此以有用的方式利用其特殊和潜在有价值的生物分子结合特性。这会导致“筛选范围”
• 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。
• Optimization of (Phenylmethylidene)-hydantoins as Prostate Cancer Migration Inhibitors: SAR-Directed Design, Synthesis, and Pharmacophore Modeling
  作者：Mudit Mudit、Khalid A. El Sayed

  DOI：10.1002/cbdv.201000248

  日期：2011.8

  properties against the highly invasive prostate cancer. To further optimize the activity of PMHs, various ligand‐based strategies were used including the extension of the structure, structural simplification, linker extension, and computer‐assisted CoMFA (Comparative Molecular Field Analysis) results. These strategies yielded thirty 2nd‐generation PMHs, designed based on the 1st‐generation PMHs, such

  前列腺癌是西方国家男性中最常见的癌症形式之一。天然产物被证明是分子多样性的无与伦比的来源。4-(羟基苯亚甲基)乙内酰脲 (PMH; 1), (5Z)-5-(4-hydroxybenzylidene)imidazolidine-2,4-dione，从红海海绵半真菌阿拉比卡中分离出来，最近显示出连接复合物的稳定性，抗-体外和体内的侵入性和抗转移活性。相关的合成类似物，(5Z)-5-[4-(乙基硫烷基)苯亚甲基]咪唑烷-2,4-二酮 (2)，显示出对高侵袭性前列腺癌的体内抗转移特性提高了数倍。为了进一步优化 PMH 的活性，使用了各种基于配体的策略，包括结构扩展、结构简化、接头扩展、和计算机辅助的 CoMFA（比较分子场分析）结果。这些策略产生了 30 种基于第一代 PMH 设计的第二代 PMH，例如 1 和 2。选择伤口愈合试验来评估这些新 PMH 对 PC-3 细胞系的体外抗迁移潜力. 确定了几种活性
• Search for new tools to combat Gram-negative resistant bacteria among amine derivatives of 5-arylidenehydantoin
  作者：Jadwiga Handzlik、Ewa Szymańska、Sandrine Alibert、Jacqueline Chevalier、Ewa Otrębska、Elżbieta Pękala、Jean-Marie Pagès、Katarzyna Kieć-Kononowicz

  DOI：10.1016/j.bmc.2012.10.053

  日期：2013.1

  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.
• 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.