(5Z)-5-[(4-hydroxy-3,5-dimethylphenyl)methylidene]-1,3-thiazolidine-2,4-dione | 741712-14-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (5Z)-5-[(4-hydroxy-3,5-dimethylphenyl)methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 741712-14-1
• 化学式: C₁₂H₁₁NO₃S
• 分子量: 249.29
• InChiKey: ZOJCQUMIKFJCPG-UITAMQMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  91.7
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  trifluoromethanesulfonic acid 1-methyl-cyclohexylmethyl ester 、 (5Z)-5-[(4-hydroxy-3,5-dimethylphenyl)methylidene]-1,3-thiazolidine-2,4-dione 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 (Z)-5-(4-hydroxy-3,5-dimethylbenzylidene)-3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione
  参考文献：
  名称：

  Pharmacological Exploitation of the Peroxisome Proliferator-Activated Receptor γ Agonist Ciglitazone To Develop a Novel Class of Androgen Receptor-Ablative Agents

  摘要：

  On the basis of our finding that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist ciglitazone at high doses was able to mediate PPAR gamma-independent transcriptional repression of androgen receptor (AR) in a tumor cell-specific manner, we used Delta 2CG, a PPAR gamma-inactive analogue of ciglitazone, to conduct lead optimization to develop a novel class of AR-ablative agents. Structure-activity analysis indicates a high degree of flexibility in realigning Delta 2CG's structural moieties without compromising potency in AR repression, as evidenced by the higher AR-ablative activity of the permuted isomer 9 [(Z)-5-(4-hydroxybenzylidene)3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione]. Further modificiations of 9 gave rise to 12 [(Z)-5-(4-hydroxy-3-trifluoromethylbenzylidene)-3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione], which completely inhibited AR expression in LNCaP cells at low micromolar concentrations. This AR down-regulation led to growth inhibition in LNCaP cells through apoptosis induction. Moreover, the role of AR repression in the antiproliferative effect of compound 12 was validated by the differential inhibition of cell viability between androgen-responsive and androgen-nonresponsive cells.

  DOI：

  10.1021/jm701212m
• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 3,5-二甲基-4-羟基苯甲醛 在 哌啶 作用下， 以 乙醇 为溶剂， 以80%的产率得到(5Z)-5-[(4-hydroxy-3,5-dimethylphenyl)methylidene]-1,3-thiazolidine-2,4-dione
  参考文献：
  名称：

  Inhibitory effects of multi-substituted benzylidenethiazolidine-2,4-diones on LDL oxidation

  摘要：

  Multi-substituted benzylidenethiazolidine-2,4-diones 3a-h were synthesized by Knoevenagel condensation of di- or tri-substituted 4-hydroxybenzaldehydes [or 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone] 1 with thiazolidine-2,4-dione (2) and evaluated for antioxidant activities of Cu2+-induced oxidation of human low-density lipoproteins (LDL). Among compounds 3a-h, 3a was superior to probucol in LDL-antioxidant activities and found to be ninefold more active than probucol. Due to its potency, compound 3a was tested for complementary in vitro investigations, such as TBARS assay (IC50 = 0.1 muM), lag time (240 min at 1.5 muM), relative electrophoretic mobility (REM) of ox-LDL (inhibition of 83% at 10 muM), fragmentation of apoB-100 (inhibition of 61% at 5 muM), and radical DPPH scavenging activity on copper-mediated LDL oxidation. In macro phage-mediated LDL oxidation, the TBARS formation was also inhibited by compound 3a. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.001

文献信息

• Inhibitory effects of multi-substituted benzylidenethiazolidine-2,4-diones on LDL oxidation
  作者：Tae-Sook Jeong、Ju-Ryoung Kim、Kyung Soon Kim、Kyung-Hyun Cho、Ki-Hwan Bae、Woo Song Lee

  DOI：10.1016/j.bmc.2004.06.001

  日期：2004.8.1

  Multi-substituted benzylidenethiazolidine-2,4-diones 3a-h were synthesized by Knoevenagel condensation of di- or tri-substituted 4-hydroxybenzaldehydes [or 1-(3,5-di-tert-butyl-4-hydroxyphenyl)ethanone] 1 with thiazolidine-2,4-dione (2) and evaluated for antioxidant activities of Cu2+-induced oxidation of human low-density lipoproteins (LDL). Among compounds 3a-h, 3a was superior to probucol in LDL-antioxidant activities and found to be ninefold more active than probucol. Due to its potency, compound 3a was tested for complementary in vitro investigations, such as TBARS assay (IC50 = 0.1 muM), lag time (240 min at 1.5 muM), relative electrophoretic mobility (REM) of ox-LDL (inhibition of 83% at 10 muM), fragmentation of apoB-100 (inhibition of 61% at 5 muM), and radical DPPH scavenging activity on copper-mediated LDL oxidation. In macro phage-mediated LDL oxidation, the TBARS formation was also inhibited by compound 3a. (C) 2004 Elsevier Ltd. All rights reserved.
• Pharmacological Exploitation of the Peroxisome Proliferator-Activated Receptor γ Agonist Ciglitazone To Develop a Novel Class of Androgen Receptor-Ablative Agents
  作者：Jian Yang、Shuo Wei、Da-Sheng Wang、Yu-Chieh Wang、Samuel K. Kulp、Ching-Shih Chen

  DOI：10.1021/jm701212m

  日期：2008.4.1

  On the basis of our finding that the peroxisome proliferator-activated receptor gamma (PPAR gamma) agonist ciglitazone at high doses was able to mediate PPAR gamma-independent transcriptional repression of androgen receptor (AR) in a tumor cell-specific manner, we used Delta 2CG, a PPAR gamma-inactive analogue of ciglitazone, to conduct lead optimization to develop a novel class of AR-ablative agents. Structure-activity analysis indicates a high degree of flexibility in realigning Delta 2CG's structural moieties without compromising potency in AR repression, as evidenced by the higher AR-ablative activity of the permuted isomer 9 [(Z)-5-(4-hydroxybenzylidene)3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione]. Further modificiations of 9 gave rise to 12 [(Z)-5-(4-hydroxy-3-trifluoromethylbenzylidene)-3-(1-methylcyclohexylmethyl)thiazolidine-2,4-dione], which completely inhibited AR expression in LNCaP cells at low micromolar concentrations. This AR down-regulation led to growth inhibition in LNCaP cells through apoptosis induction. Moreover, the role of AR repression in the antiproliferative effect of compound 12 was validated by the differential inhibition of cell viability between androgen-responsive and androgen-nonresponsive cells.