(Z)-5-[4-(1-methylcyclohexylmethoxy)-3-nitrobenzylidene]thiazolidine-2,4-dione | 1020066-67-4

• 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-(1-methylcyclohexylmethoxy)-3-nitrobenzylidene]thiazolidine-2,4-dione
• 英文别名: (5Z)-5-[[4-[(1-methylcyclohexyl)methoxy]-3-nitrophenyl]methylidene]-1,3-thiazolidine-2,4-dione
• CAS: 1020066-67-4
• 化学式: C₁₈H₂₀N₂O₅S
• 分子量: 376.433
• InChiKey: SVDOFUZAXYHSGF-GDNBJRDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  2,4-噻唑烷二酮 、 C₁₅H₁₉NO₄ 在 哌啶 作用下， 以 乙醇 为溶剂， 生成 (Z)-5-[4-(1-methylcyclohexylmethoxy)-3-nitrobenzylidene]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

• ANDROGEN RECEPTOR-ABLATIVE AGENTS
  申请人：The Ohio State University Research Foundation

  公开号：EP2254576B1

  公开（公告）日：2013-08-28