(5Z)-5-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-3-[(1-methylcyclohexyl)methyl]-1,3-thiazolidine-2,4-dione | 1020066-81-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 酚类
• 英文名称: (5Z)-5-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-3-[(1-methylcyclohexyl)methyl]-1,3-thiazolidine-2,4-dione
• CAS: 1020066-81-2
• 化学式: C₁₈H₁₉Br₂NO₃S
• 分子量: 489.228
• InChiKey: NPEVASITUZUIKK-ZROIWOOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  82.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(3,5-Dibromo-4-hydroxy-benzylidene)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 (5Z)-5-[(3,5-dibromo-4-hydroxyphenyl)methylidene]-3-[(1-methylcyclohexyl)methyl]-1,3-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 DERIVATIVES, PREPARATION THEREOF AND USE THEREOF IN CANCER TREATMENT
  申请人：Boisbrun Michel

  公开号：US20140364465A1

  公开（公告）日：2014-12-11

  The present invention relates to thiazolidinedione derivatives, to the processes for preparing same and to the therapeutic use thereof for preventing or treating cancer, and more specifically breast cancer. These compounds are of formula (I) and exhibit, at a concentration of 100 μM, a hepatocyte viability preferably greater than 60%, preferably greater than 80% and more preferentially greater than 85%.

  本发明涉及噻唑烷二酮衍生物、其制备方法以及预防或治疗癌症（更具体地说是乳腺癌）的治疗用途。这些化合物的化学式为（I），在浓度为100μM时，具有肝细胞存活率优选大于60％，更优选大于80％，最优选大于85％。
• 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。
• ANDROGEN RECEPTOT-ABLATIVE AGENTS
  申请人：The Ohio State University Research Foundation

  公开号：EP2254576A1

  公开（公告）日：2010-12-01
• DÉRIVÉS DE THIAZOLIDINEDIONE, LEUR PRÉPARATION ET LEUR UTILISATION DANS LE TRAITEMENT DES CANCERS
  申请人：Université de Lorraine

  公开号：EP2838899B1

  公开（公告）日：2016-10-05