(Z)-5-[4-hydroxy-3-(trifluoromethyl)benzylidene]-3-[(1-methylcyclohexyl)methyl]thiazolidine-2,4-dione | 1020066-77-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (Z)-5-[4-hydroxy-3-(trifluoromethyl)benzylidene]-3-[(1-methylcyclohexyl)methyl]thiazolidine-2,4-dione
• 英文别名: Osu-CG12；(5Z)-5-[[4-hydroxy-3-(trifluoromethyl)phenyl]methylidene]-3-[(1-methylcyclohexyl)methyl]-1,3-thiazolidine-2,4-dione
• CAS: 1020066-77-6
• 化学式: C₁₉H₂₀F₃NO₃S
• 分子量: 399.434
• InChiKey: MADFJWDIMPOGOZ-GDNBJRDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (Z)-5-[4-hydroxy-3-(trifluoromethyl)benzylidene]-3-[(1-methylcyclohexyl)methyl]thiazolidine-2,4-dione 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 以14 mg的产率得到5-(4-hydroxy-3-trifluoromethylbenzyl)-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：

  (5Z)-5-[[4-hydroxy-3-(trifluoromethyl)phenyl]methylidene]-1,3-thiazolidine-2,4-dione 、 trifluoromethanesulfonic acid 1-methyl-cyclohexylmethyl ester 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-(trifluoromethyl)benzylidene]-3-[(1-methylcyclohexyl)methyl]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

文献信息

• [EN] ANDROGEN RECEPTOT-ABLATIVE AGENTS<br/>[FR] AGENTS ABLATIFS DU RÉCEPTEUR ANDROGÈNE
  申请人：UNIV OHIO STATE RES FOUND

  公开号：WO2009105621A1

  公开（公告）日：2009-08-27

  Compounds of the thiazolidinedione family are provided and shown to be effective androgen receptor ablative agents that can be used in methods of treating or preventing cancer or precancer, including prostate cancer. Also provided are methods of treating or preventing cancer by administering a therapeutically effective amount of one of the androgen receptor ablative agents to a subject in need of such treatment.

  提供了噻唑烷二酮家族的化合物，并证明其是有效的雄激素受体消融剂，可用于治疗或预防癌症或癌前病变，包括前列腺癌的方法。还提供了通过向需要此类治疗的受试者施用治疗有效量的雄激素受体消融剂的方法，用于治疗或预防癌症的方法。
• THIAZOLIDINEDIONE ENERGY RESTRICTION-MIMETIC AGENTS
  申请人：Chen Ching-Shih

  公开号：US20110086895A1

  公开（公告）日：2011-04-14

  A method of inhibiting glycolysis in a subject by administering a pharmaceutical composition including a thiazolidinedione derivative to the subject is described. The thiazolidinedione derivatives are effective energy restriction mimetic agents, and can therefore be used to treat or prevent cancer in a subject, treat metabolic disorder, or increase the longevity of a subject. Various thiazolidinedione derivatives are also suitable for activating adenosine phosphate-activated protein kinase or inhibiting IL-6 expression.

  本发明涉及一种通过向受体给予包含噻唑烷二酮衍生物的药物组合物来抑制其糖酵解的方法。噻唑烷二酮衍生物是有效的能量限制模拟剂，因此可用于治疗或预防受体的癌症，治疗代谢性疾病或延长受体的寿命。各种噻唑烷二酮衍生物也适用于激活腺苷酸磷酸激活的蛋白激酶或抑制IL-6表达。
• ANDROGEN RECEPTOR-ABLATIVE AGENTS
  申请人：Chen Ching-Shih

  公开号：US20090291992A1

  公开（公告）日：2009-11-26

  Compounds of the thiazolidinedione family are provided and shown to be effective androgen receptor ablative agents that can be used in methods of treating or preventing cancer or precancer, including prostate cancer. Also provided are methods of treating or preventing cancer by administering a therapeutically effective amount of one of the androgen receptor ablative agents to a subject in need of such treatment.

  提供了噻唑烷二酮家族的化合物，并证明其是有效的雄激素受体抑制剂，可用于治疗或预防癌症或癌前状态，包括前列腺癌的方法。还提供了通过向需要此类治疗的受试者施用治疗剂量的雄激素受体抑制剂之一来治疗或预防癌症的方法。
• Thiazolidinedione energy restriction-mimetic agents
  申请人：Chen Ching-Shih

  公开号：US08383656B2

  公开（公告）日：2013-02-26

  A method of inhibiting glycolysis in a subject by administering a pharmaceutical composition including a thiazolidinedione derivative to the subject is described. The thiazolidinedione derivatives are effective energy restriction mimetic agents, and can therefore be used to treat or prevent cancer in a subject, treat metabolic disorder, or increase the longevity of a subject. Various thiazolidinedione derivatives are also suitable for activating adenosine phosphate-activated protein kinase or inhibiting IL-6 expression.

  本文描述了一种通过向主体施用包含噻唑烷二酮衍生物的药物组合物来抑制糖酵解的方法。噻唑烷二酮衍生物是有效的能量限制模拟剂，因此可用于治疗或预防主体的癌症，治疗代谢紊乱或延长主体的寿命。各种噻唑烷二酮衍生物也适用于激活腺苷酸磷酸激活蛋白激酶或抑制IL-6表达。
• GLUCOSE TRANSPORTER INHIBITORS
  申请人：The Ohio State University Research Foundation

  公开号：US20150051255A1

  公开（公告）日：2015-02-19

  Thiazolidinedione compounds and pharmaceutically acceptable salts thereof are described. The compounds can be used in methods of treating cancer in a subject by administering to the subject a therapeutically effective amount of the compound. The compounds can also be used in methods of inhibiting glucose uptake in a cell by contacting the cell with the compound.