2-(4-oxo-2-thioxothiazolidin-3-yl)pentanedioic acid

• 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-(4-oxo-2-thioxothiazolidin-3-yl)pentanedioic acid
• 英文别名: (2S)-2-(4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl)pentanedioic acid
• 化学式: C₈H₉NO₅S₂
• 分子量: 263.295
• InChiKey: ONCPOKGRSJBOQM-BYPYZUCNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  152
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-oxo-2-thioxothiazolidin-3-yl)pentanedioic acid 、 3-吲哚甲醛 在 ammonium acetate 作用下， 以 乙醇 为溶剂， 以99%的产率得到(Z)-2-[5-(1H-indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl]pentanedioic acid
  参考文献：
  名称：

  5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl) 链烷羧酸作为抗菌剂：合成、生物学评价和分子对接研究

  摘要：

  背景：传染病象征着全球对公共卫生安全造成的后果性压力，并对世界各地的社会经济稳定产生影响。对当前抗菌治疗的耐药性日益增加，迫切需要发现和开发具有不同作用模式的感染治疗新实体，这些实体可以同时针对敏感菌株和耐药菌株。方法：使用有机合成的经典方法合成化合物。结果：所有 20 种合成化合物均显示出对 8 种革兰氏阳性和革兰氏阴性细菌的抗菌活性。应该提到的是，所有化合物对所有测试的细菌都表现出比氨苄青霉素更好的抗菌效力。此外，18 种化合物似乎比链霉素更有效地对抗金黄色葡萄球菌、阴沟肠杆菌、铜绿假单胞菌、单核细胞增生李斯特菌和大肠杆菌。三种最活跃的化合物 4h、5b 和 5g 似乎比氨苄青霉素更有效地对抗 MRSA，而链霉素没有显示任何杀菌活性。与氨苄青霉素相比，所有三种化合物对铜绿假单胞菌和大肠杆菌的耐药菌株也显示出更好的活性。此外，所有化合物都能够比两种参考药物抑制生物膜形成多 2 到 4 倍

  DOI：

  10.3390/molecules25081964
• 作为产物：
  描述：

  在 盐酸 作用下， 以 水 为溶剂， 反应 1.0h， 生成 2-(4-oxo-2-thioxothiazolidin-3-yl)pentanedioic acid
  参考文献：
  名称：

  5-(1H-Indol-3-ylmethylene)-4-oxo-2-thioxothiazolidin-3-yl) 链烷羧酸作为抗菌剂：合成、生物学评价和分子对接研究

  摘要：

  背景：传染病象征着全球对公共卫生安全造成的后果性压力，并对世界各地的社会经济稳定产生影响。对当前抗菌治疗的耐药性日益增加，迫切需要发现和开发具有不同作用模式的感染治疗新实体，这些实体可以同时针对敏感菌株和耐药菌株。方法：使用有机合成的经典方法合成化合物。结果：所有 20 种合成化合物均显示出对 8 种革兰氏阳性和革兰氏阴性细菌的抗菌活性。应该提到的是，所有化合物对所有测试的细菌都表现出比氨苄青霉素更好的抗菌效力。此外，18 种化合物似乎比链霉素更有效地对抗金黄色葡萄球菌、阴沟肠杆菌、铜绿假单胞菌、单核细胞增生李斯特菌和大肠杆菌。三种最活跃的化合物 4h、5b 和 5g 似乎比氨苄青霉素更有效地对抗 MRSA，而链霉素没有显示任何杀菌活性。与氨苄青霉素相比，所有三种化合物对铜绿假单胞菌和大肠杆菌的耐药菌株也显示出更好的活性。此外，所有化合物都能够比两种参考药物抑制生物膜形成多 2 到 4 倍

  DOI：

  10.3390/molecules25081964

文献信息

• Synthesis, antiproliferative activity and docking study of novel rhodanine derivatives as Bcr-Abl T1351 inhibitors
  作者：Sulaiman Ali Muhammad、Subban Ravi、Arumugam Thangamani、Balakumar Chandrasekaran、M. Ramesh

  DOI：10.1007/s11164-017-2968-6

  日期：2017.10

  A series of novel N -substituted rhodanines 6a–g were synthesized by a microwave synthesizer, and evaluated for their anti-proliferative activity. Most of the compounds showed inhibition against K562 cells in a dose-dependent manner and in particular compounds 6a , 6b and 6f exhibited most potent activity with an IC50 value of 19.62, 24.01 and 22.91 µg/ml by MTT assay. Further in silico docking studies

  用微波合成仪合成了一系列新型的 N- 取代的罗丹 酮6a-g ，并评估了它们的抗增殖活性。大多数化合物显示出对K562细胞的抑制作用，呈剂量依赖性，特别是化合物 6a ， 6b 和 6f 表现出最强的活性，通过MTT分析，IC 50值为19.62、24.01和22.91 µg / ml。上述化合物对Bcr-Abl T1351蛋白的进一步计算机对接研究显示出良好的结合亲和力，因此表明该化合物表现为第三代抑制剂。用 6a–g 治疗后，LDH释放的剂量依赖性增加 补充了MTT分析的抗增殖活性。 6a的 流式细胞术 显示它通过指示G1期阻滞然后凋亡来干扰细胞分裂。
• Synthesis and evaluation of some novel N-substituted rhodanines for their anticancer activity
  作者：Sulaiman Ali Muhammad、Subban Ravi、Arumugam Thangamani

  DOI：10.1007/s00044-016-1545-7

  日期：2016.5

  Novel N-substituted rhodanines 2a–g were synthesized by conventional and microwave-assisted methods and tested for their anticancer activity. Structure–activity relationship of the synthesized rhodanine 2a–g as antiproliferative agents was investigated. The results revealed that all the seven compounds showed potent antiproliferative activity in a concentration-dependent manner on leukemic cell line

  通过常规方法和微波辅助方法合成了新型的N-取代的罗丹酮2a - g，并测试了其抗癌活性。研究了合成的若丹宁2a - g作为抗增殖剂的结构-活性关系。结果表明，所有七种化合物对白血病细胞株K562均具有浓度依赖性的有效抗增殖活性。在测试的化合物中，与锥虫蓝和MTT分析相比，发现2b更有效。IC 50值为2b使用锥虫蓝和MTT分析的结果分别为11.1和20.3 µg / ml。用2a - g处理后，还观察到LDH释放的剂量依赖性增加。细胞周期分析表明2b影响DNA复制并导致细胞在G 0中积累，并降低G 2 / M，G 1和S期，这表明细胞凋亡。通过凋亡对人类慢性骨髓细胞系（K562）的选择性细胞毒活性表明，化合物2b是开发新型抗癌药物的有希望的支架。
• Synthesis and Evaluation of Chiral Rhodanine Derivatives Bearing Quinoxalinyl Imidazole Moiety as ALK5 Inhibitors
  作者：Chang Ji Zheng、Cheng Hua Jin、Li-Min Zhao、Fang Yan Guo、Hui Min Wang、Tong Dou、Jun Da Qi、Wen Bo Xu、Lianxun Piao、Xuejun Jin、Fen-Er Chen、Hu-Ri Piao

  DOI：10.2174/1573406417666210628144849

  日期：2022.5

  synthesized and evaluated for their ALK5 inhibitory and antimicrobial activity. The structures were confirmed by their 1H NMR, 13C NMR and HRMS spectra. All the synthesized compounds were screened against Grampositive strains, Gram-negative strains, and fungi. RESULTS Among the synthesized compounds, compound 12h showed the highest activity (IC50 = 0.416 μM) against ALK5 kinase. Compound 12h exhibited

  背景技术抑制TGF-β信号通路被认为是预防多种疾病发展的有效方法。在 TGF-β 抑制剂的设计和合成中，发现含有喹喔啉基咪唑部分的罗丹宁化合物具有很强的抗菌活性。目的 这项工作的目的是研究合成的其他手性罗丹宁 TGF-β 抑制剂的抗菌活性。方法 两个系列的3-取代-5-(5-(6-methylpyridin-2-yl)-4-(quinoxalinyl-6-yl)-1Himidazol-2-yl)methylene)-2-thioxothiazolin-4-ones (合成了 12a-h 和 13a-e) 并评估了它们的 ALK5 抑制和抗菌活性。通过它们的 1H NMR、13C NMR 和 HRMS 光谱证实了这些结构。所有合成的化合物都针对革兰氏阳性菌株、革兰氏阴性菌株和真菌进行了筛选。结果在合成的化合物中，化合物12h对ALK5激酶的活性最高（IC50 = 0.416 μM）。化合物 12h
• Synthesis and antibacterial evaluation of rhodanine-based 5-aryloxy pyrazoles against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA)
  作者：Ming-Xia Song、Chang-Ji Zheng、Xian-Qing Deng、Liang-Peng Sun、Yan Wu、Lan Hong、Ying-Jing Li、Yi Liu、Zhi-Yu Wei、Ming-Jun Jin、Hu-Ri Piao

  DOI：10.1016/j.ejmech.2012.12.007

  日期：2013.2

  With an intention to synergize the anti-bacterial activity of 5-aryloxy pyrazole and rhodanine derivatives, eight series of hybrid compounds have been synthesized and evaluated for their antibacterial activity. The majority of the synthesized compounds showed good inhibitory activity against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA, QRSA) with minimum inhibitory concentration (MIC) values in the range of 1-32 mu g/mL. The cytotoxicity test suggests that these compounds exhibited in vitro antibacterial activity at non-cytotoxic concentrations. These studies therefore suggest that rhodanine-based 5-aryloxy pyrazoles are interesting scaffolds for the development of novel Gram-positive antibacterial agents. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1
  作者：Chengguo Xing、Liangyou Wang、XiaoHu Tang、Yuk Y. Sham

  DOI：10.1016/j.bmc.2006.12.020

  日期：2007.3

  A series of inhibitors for anti-apoptotic Bcl-2 proteins based on BHI-1 were synthesized and their binding interactions with Bcl-2. Bcl-X-L, and Bcl-w were evaluated. It was found that modification of BHI-1 resulted in varied binding profiles among Bcl-2, Bcl-XL, and Bcl-w, and a set of inhibitors with varied selectivity to Bcl-2, Bcl-X-L, and Bcl-w proteins have been identified. Molecular modeling of the interaction of the BHI-1 based analogues with the anti-apoptotic Bcl-2 proteins suggested that the binding site for the BHI-1 based inhibitor was the least conserved section among Bcl-2, Bcl-X-L, and Bcl-w: targeting the non-conserved section may account for the observed selectivity of the BHI-1 based inhibitors among the anti-apoptotic Bcl-2 proteins. The validity of the model was supported by a strong correlation between the model-calculated binding energy and the experimental binding affinity. In summary, our studies suggest that most of the reported inhibitors for anti-apoptotic Bcl-2 proteins are nonselective and BHI-1 is a promising template to distinguish among Bcl-2, Bcl-X-L, and Bcl-w by targeting the non-conserved domain among the anti-apoptotic Bcl-2 proteins. Molecular-modeling-aided rational development of BHI-1 based selective inhibitor for antiapoptotic Bcl-2 proteins is underway. Published by Elsevier Ltd.