2-(5-oxo-2-thioxoimidazolidin-1-yl) acetic acid | 119681-50-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(5-oxo-2-thioxoimidazolidin-1-yl) acetic acid
• 英文别名: 2-(5-oxo-2-thioxoimidazolidin-1-yl)acetic acid；2-thiohydantoin-3-acetic acid；(5-oxo-2-thioxo-imidazolidin-1-yl)-acetic acid；(5-Oxo-2-thioxo-imidazolidin-1-yl)-essigsaeure；(5-Oxo-2-thioxo-1-imidazolidinyl)acetic acid；2-(5-oxo-2-sulfanylideneimidazolidin-1-yl)acetic acid
• CAS: 119681-50-4
• 化学式: C₅H₆N₂O₃S
• 分子量: 174.18
• InChiKey: DNSFRCSKVRZADF-UHFFFAOYSA-N

物化性质

• 熔点：
  138 °C (decomp)
• 沸点：
  341.2±44.0 °C(Predicted)
• 密度：
  1.66±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(5-oxo-2-thioxoimidazolidin-1-yl) acetic acid 在 氢氧化钾 、 sodium acetate 、 乙酸酐 作用下， 以 溶剂黄146 为溶剂， 反应 0.25h， 生成 potassium 2-(4-(4-chlorobenzylidene)-2-(methylthio)-5-oxo-4,5-dihydro-1H-imidazol-1-yl)acetate
  参考文献：
  名称：

  Korohoda, Maria Jolanta, Polish Journal of Chemistry, 1981, vol. 55, # 2, p. 359 - 369

  摘要：

  DOI：
• 作为产物：
  描述：

  N,N'-thiocarbonyl-bis-glycine diethyl ester 在 盐酸 作用下， 生成 2-(5-oxo-2-thioxoimidazolidin-1-yl) acetic acid
  参考文献：
  名称：

  Johnson; Renfrew, Journal of the American Chemical Society, 1925, vol. 47, p. 244

  摘要：

  DOI：

文献信息

• Systematic Evaluation of the Metabolism and Toxicity of Thiazolidinone and Imidazolidinone Heterocycles
  作者：Shi Qing Tang、Yong Yang Irvin Lee、David Sheela Packiaraj、Han Kiat Ho、Christina Li Lin Chai

  DOI：10.1021/acs.chemrestox.5b00247

  日期：2015.10.19

  The thiazolidine and imidazolidine heterocyclic scaffolds, i.e., the rhodanines, 2,4-thiazolidinediones, 2-thiohydantoins, and hydantoins have been the subject of debate on their suitability as starting points in drug discovery. This attention arose from the wide variety of biological activities exhibited by these scaffolds and their frequent occurrence as hits in screening campaigns. Studies have been conducted to evaluate their value in drug discovery in terms of their biological activity, chemical reactivity, aggregation-based promiscuity, and electronic properties. However, the metabolic profiles and toxicities have not been systematically assessed. In this study, a series of five-membered multiheterocyclic (FMMH) compounds were selected for a systematic evaluation of their metabolic profiles and toxicities on TAMH cells, a metabolically competent rodent liver cell line and HepG2 cells, a model of human hepatocytes. Our studies showed that generally the rhodanines are the most toxic, followed by the thiazolidinediones, thiohydantoins, and hydantoins. However, not all compounds within the family of heterocycles were toxic. In terms of metabolic stability, 5-substituted rhodanines and 5-benzylidene thiohydantoins were found to have short half-lives in the presence of human liver microsomes (t1/2 < 30 min) suggesting that the presence of the endocyclic sulfur and thiocarbonyl group or a combination of C5 benzylidene substituent and thiocarbonyl group in these heterocycles could be recognition motifs for P450 metabolism. However, the stability of these compounds could be improved by installing hydrophilic functional groups. Therefore, the toxicities and metabolic profiles of FMMH derivatives will ultimately depend on the overall chemical entity, and a blanket statement on the effect of the FMMH scaffold on toxicity or metabolic stability cannot and should not be made.

  噻唑烷和咪唑烷杂环骨架，即罗丹宁、2,4-噻唑烷二酮、2-硫代海因和海因，其作为药物发现的起始点的适宜性一直是争论的主题。这种关注源于这些骨架所展现的多样化的生物活性和它们在筛选活动中频繁出现作为命中物。已经进行了研究来评估它们在药物发现中的价值，包括它们的生物活性、化学反应性、基于聚集的杂乱性以及电子性质。然而，它们的代谢轮廓和毒性尚未被系统地评估。在这项研究中，选择了一系列五元多杂环（FMMH）化合物，对它们在TAMH细胞（一种代谢能力健全的啮齿动物肝细胞系）和HepG2细胞（一种人肝细胞模型）上的代谢轮廓和毒性进行了系统评估。我们的研究表明，一般来说，罗丹宁的毒性最大，其次是噻唑烷二酮、硫代海因和海因。然而，并非所有杂环家族中的化合物都具有毒性。在代谢稳定性方面，发现5-取代的罗丹宁和5-苄叉基硫代海因在人肝微粒体存在下具有较短的半衰期（t1/2 < 30分钟），这表明在这些杂环中的环内硫和硫羰基或5位苄叉基取代和硫羰基的组合可能是P450代谢的识别基序。然而，通过引入亲水性功能基团可以提高这些化合物的稳定性。因此，FMMH衍生物的毒性和代谢轮廓最终将取决于整体化学实体，关于FMMH骨架对毒性或代谢稳定性的影响不能也不应该做出笼统的陈述。
• 含杂环的联芳基噁唑烷酮化合物及其制备方 法
  申请人：沈阳药科大学

  公开号：CN108976222B

  公开（公告）日：2021-09-03

  本发明涉及通式Ⅰ所示的含杂环的联芳基噁唑烷酮类化合物，或其旋光异构体、药学上可接受的盐和/或溶剂化物，它们的制备方法以及含有所述化合物的药物组合物。其中取代基R1、R2、R3、R4及A环具有在说明书中给出的含义。本发明还涉及该类化合物及其药学上可接受的盐、溶剂化物或其前药在治疗中作为抗菌药的用途，特别是在治疗革兰阳性菌感染及结核杆菌感染中的用途。
• Highly efficient microwave synthesis of rhodanine and 2-thiohydantoin derivatives and determination of relationships between their chemical structures and antibacterial activity
  作者：Waldemar Tejchman、Bartosz Orwat、Izabela Korona-Głowniak、Anna Barbasz、Ireneusz Kownacki、Gniewomir Latacz、Jadwiga Handzlik、Ewa Żesławska、Anna Malm

  DOI：10.1039/c9ra08690k

  日期：——

  Here we report studies on the synthesis of 12 new heterocyclic derivatives that differ in three structural motifs and the simultaneous evaluation of the impact of these three variables on the biological properties. The examined compounds are based on rhodanine and 2-thiohydantoin cores equipped with hydrogen or carboxymethyl substituents at the N-3 position and linked to a triphenylamine moiety through

  在这里，我们报告了 12 种在三个结构基元上不同的新杂环衍生物的合成研究，并同时评估了这三个变量对生物学特性的影响。所研究的化合物基于罗丹宁和 2-硫代乙内酰脲核心，在 N-3 位配备氢或羧甲基取代基，并通过 1,4-亚苯基、1,4-亚萘基和 1,9-亚蒽基间隔物连接到三苯胺部分杂环的 C-5 位。根据开发的微波辅助 Knoevenagel 缩合方案，所有化合物都非常快速、选择性和高产率地合成，并使用 NMR、FT-IR 和 ESI-HRMS 技术对其进行了彻底的表征。测试了这些衍生物对选定的革兰氏阳性和革兰氏阴性细菌和酵母菌株的活性。两种化合物对革兰氏阳性菌表现出良好的活性，对三种人体免疫系统细胞系均表现出低细胞毒性。基于膜渗透性测定，证明活性化合物不会穿透细胞膜，因此它们必须作用于细菌细胞表面。最后，我们证明了所评估的结构修饰具有协同作用，并且在 N-3 处同时存在 1,4-亚苯基间隔
• AMINO ACIDS: IV. THE REACTION OF GLYCINE AND β-ALANINE WITH CARBON DISULPHIDE
  作者：E. J. Tarlton、A. F. McKay

  DOI：10.1139/v58-071

  日期：1958.3.1

  Glycine and β-alanine on condensation with carbon disulphide gave the corresponding l,3-di-(carboxyalkyl) thioureas. l,3-Di-(carboxymethyl) thiourea is rearranged to 2-thio-3-(carboxymethyl) hydant...

  甘氨酸和β-丙氨酸与二硫化碳缩合得到相应的1,3-二-(羧烷基)硫脲。l,3-Di-(carboxymethyl) thiourea 重排为 2-thio-3-(carboxymethyl) hydrant...
• Preliminary Studies of Antimicrobial Activity of New Synthesized Hybrids of 2-Thiohydantoin and 2-Quinolone Derivatives Activated with Blue Light
  作者：Agnieszka Kania、Waldemar Tejchman、Anna M. Pawlak、Krystian Mokrzyński、Bartosz Różanowski、Bogdan M. Musielak、Magdalena Greczek-Stachura

  DOI：10.3390/molecules27031069

  日期：——

  Thiohydantoin and quinolone derivatives have attracted researchers’ attention because of a broad spectrum of their medical applications. The aim of our research was to synthesize and analyze the antimicrobial properties of novel 2-thiohydantoin and 2-quinolone derivatives. For this purpose, two series of hybrid compounds were synthesized. Both series consisted of 2-thiohydantoin core and 2-quinolone derivative ring, however one of them was enriched with an acetic acid group at N3 atom in 2-thiohydantoin core. Antibacterial properties of these compounds were examined against bacteria: Staphylococcus aureus, Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae. The antimicrobial assay was carried out using a serial dilution method to obtain the MIC. The influence of blue light irradiation on the tested compounds was investigated. The relative yield of singlet oxygen (1O2*, 1Δg) generation upon excitation with 420 nm was determined by a comparative method, employing perinaphthenone (PN) as a standard. Antimicrobial properties were also investigated after blue light irradiation of the suspensions of the hybrids and bacteria placed in microtitrate plates. Preliminary results confirmed that some of the hybrid compounds showed bacteriostatic activity to the reference Gram-positive bacterial strains and a few of them were bacteriostatic towards Gram-negative bacteria, as well. Blue light activation enhanced bacteriostatic effect of the tested compounds.

  硫代异噻唑酮和喹诺酮衍生物因其广泛的医学应用而吸引了研究人员的关注。我们研究的目的是合成和分析新型2-硫代异噻唑酮和2-喹诺酮衍生物的抗菌性能。为此，我们合成了两系列混合化合物。两个系列都由2-硫代异噻唑酮核心和2-喹诺酮衍生物环组成，但其中一个在2-硫代异噻唑酮核心的N3原子上富集了乙酸基团。这些化合物的抗菌性能被检测了对抗细菌：金黄色葡萄球菌、枯草杆菌、肠球菌、大肠杆菌、铜绿假单胞菌和肺炎克雷伯菌。采用连续稀释法进行抗菌试验以获得最小抑菌浓度（MIC）。研究了蓝光照射对测试化合物的影响。比较法测定了在420 nm激发下产生单线态氧（1O2*，1Δg）的相对产率，采用过氧化萘酮（PN）作为标准。在微孔板中放置混合物和细菌的悬浮液后，还研究了蓝光照射后的抗菌性能。初步结果证实，一些混合物对参考的革兰氏阳性细菌菌株表现出细菌抑制活性，其中有一些对革兰氏阴性细菌也具有细菌抑制作用。蓝光激活增强了测试化合物的细菌抑制效果。