(S)-3-methyl-2-(4-oxo-2-thioxothiazolidin-3-yl)butanoic 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: (S)-3-methyl-2-(4-oxo-2-thioxothiazolidin-3-yl)butanoic acid
• 英文别名: (2S)-3-methyl-2-(4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl)butanoic acid
• 化学式: C₈H₁₁NO₃S₂
• mdl: MFCD00457542
• 分子量: 233.312
• InChiKey: CAFMKIQOSYUXLI-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  115
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-3-methyl-2-(4-oxo-2-thioxothiazolidin-3-yl)butanoic acid 、 3-Methyl-1-phenyl-5-[3-(trifluoromethyl)phenoxy]pyrazole-4-carbaldehyde 在 哌啶 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 (2S)-3-methyl-2-[(5Z)-5-[[3-methyl-1-phenyl-5-[3-(trifluoromethyl)phenoxy]pyrazol-4-yl]methylidene]-4-oxo-2-sulfanylidene-1,3-thiazolidin-3-yl]butanoic acid
  参考文献：
  名称：

  Synthesis and antibacterial evaluation of rhodanine-based 5-aryloxy pyrazoles against selected methicillin resistant and quinolone-resistant Staphylococcus aureus (MRSA and QRSA)

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2012.12.007
• 作为产物：
  描述：

  二硫化碳 、 L-缬氨酸 、 sodium monochloroacetic acid 在 sodium hydroxide 、 盐酸 作用下， 以 水 为溶剂， 反应 15.0h， 生成 (S)-3-methyl-2-(4-oxo-2-thioxothiazolidin-3-yl)butanoic acid
  参考文献：
  名称：

  Development of selective inhibitors for anti-apoptotic Bcl-2 proteins from BHI-1

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.12.020

文献信息

• [EN] BIARYLRHODANINE AND PYRIDYLRHODANINE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS DE BIARYLRHODANINE ET DE PYRIDYLRHODANINE ET LEUR UTILISATION
  申请人：AGENCY SCIENCE TECH & RES

  公开号：WO2010024783A1

  公开（公告）日：2010-03-04

  The present invention pertains generally to the field of therapeutic compounds, and more specifically to compounds related to rhodanine, which compounds are inter alia inhibitors and/or binders of antiapoptotic/pro-survival Bcl-2 proteins such as Bcl-XL and/or Mcl-1. More specifically, the present invention is concerned with Rhodanine- based Pan-Bcl-2 inhibitors and Mcl-1 -specific inhibitors as anti-cancer compounds. The present invention also pertains to pharmaceutical compositions comprising such compounds, and the use of such compounds and compositions, both in vitro and in vivo, to inhibit and/or bind Bcl-2 proteins such as Bcl-XL and/or Mcl-1, and in the treatment of diseases and conditions that are mediated by Bcl-2 proteins, that are ameliorated by the inhibition of Bcl-2 protein function (such as Bcl-XL and/or Mcl-1 ) including proliferative conditions such as cancer, optionally in combination with another agent.

  本发明一般涉及治疗化合物领域，更具体地涉及与罗丹宁相关的化合物，这些化合物是抑制剂和/或结合剂，用于抑制和/或结合抗凋亡/促存活的Bcl-2蛋白，如Bcl-XL和/或Mcl-1。更具体地，本发明涉及基于罗丹宁的Pan-Bcl-2抑制剂和Mcl-1特异性抑制剂作为抗癌化合物。本发明还涉及包括这些化合物的药物组合物，以及在体外和体内使用这些化合物和组合物来抑制和/或结合Bcl-2蛋白，如Bcl-XL和/或Mcl-1，并用于治疗由Bcl-2蛋白介导的疾病和症状，通过抑制Bcl-2蛋白功能（如Bcl-XL和/或Mcl-1）改善的疾病和症状，包括增殖性疾病如癌症，可选择地与另一药剂联合使用。
• 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
• 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.
• 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.
• Synthesis and biological evaluation of (<i>E</i>)-1-(substituted)-3-phenylprop-2-en-1-ones bearing rhodanines as potent anti-microbial agents
  作者：Ming-Xia Song、Xian-Qing Deng、Ya-Ru Li、Chang-Ji Zheng、Lan Hong、Hu-Ri Piao

  DOI：10.3109/14756366.2013.837899

  日期：2014.10.1

  Herein, we report the design, syntheses and in vitro anti-microbial activity of two series of rhodanines with chalcone moiety. Anti-microbial tests showed that some of the synthesized compounds exhibited good inhibition (MIC = 1-8 µg/mL) against multi-drug-resistant Gram-positive organisms, including methicillin resistant and quinolone-resistant Staphylococcus aureus, in which the compound 4g was found to be the most potent with minimum inhibitory concentration (MIC) value of 1 µg/mL against two methicillin-resistant S. aureus.