4-[3,4-dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-5-methyl-2-trifluoromethylbenzonitrile | 1401225-66-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 4-[3,4-dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-5-methyl-2-trifluoromethylbenzonitrile
• 英文别名: 4-[4-(4-Hydroxyphenyl)-3,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-5-methyl-2-(trifluoromethyl)benzonitrile；4-[4-(4-hydroxyphenyl)-3,4-dimethyl-2,5-dioxoimidazolidin-1-yl]-5-methyl-2-(trifluoromethyl)benzonitrile
• CAS: 1401225-66-8
• 化学式: C₂₀H₁₆F₃N₃O₃
• 分子量: 403.361
• InChiKey: XSCIIJCWTGDBCE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  84.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  methyl 2-(4-acetoxyphenyl)-2-bromopropionate 以 四氢呋喃 、 乙醇 为溶剂， 反应 0.5h， 生成 4-[3,4-dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-5-methyl-2-trifluoromethylbenzonitrile
  参考文献：
  名称：

  Discovery of Diarylhydantoins as New Selective Androgen Receptor Modulators

  摘要：

  A novel selective androgen receptor modulator scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A(50) = 0.5 mg/kg vs 70 mg/kg). The binding modes of two compounds, including (+)-11b, within the AR ligand-binding domain have been studied by cocrystallization experiments using a coactivator-like peptide. Both compounds bound to the same site, and the overall structures of the AR were very similar.

  DOI：

  10.1021/jm300249m

文献信息

• Discovery of Diarylhydantoins as New Selective Androgen Receptor Modulators
  作者：François Nique、Séverine Hebbe、Christophe Peixoto、Denis Annoot、Jean-Michel Lefrançois、Eric Duval、Laurence Michoux、Nicolas Triballeau、Jean-Michel Lemoullec、Patrick Mollat、Maxime Thauvin、Thierry Prangé、Dominique Minet、Philippe Clément-Lacroix、Catherine Robin-Jagerschmidt、Damien Fleury、Denis Guédin、Pierre Deprez

  DOI：10.1021/jm300249m

  日期：2012.10.11

  A novel selective androgen receptor modulator scaffold has been discovered through structural modifications of hydantoin antiandrogens. Several 4-(4-hydroxyphenyl)-N-arylhydantoins displayed partial agonism with nanomolar in vitro potency in transactivation experiments using androgen receptor (AR) transfected cells. In a standard castrated male rat model, several compounds showed good anabolic activity on levator ani muscle, dissociated from the androgenic activity on ventral prostate, after oral dosing at 30 mg/kg. (+)-4-[3,4-Dimethyl-2,5-dioxo-4-(4-hydroxyphenyl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile ((+)-11b) displayed anabolic potency with a strong dissociation between levator ani muscle and ventral prostate (A(50) = 0.5 mg/kg vs 70 mg/kg). The binding modes of two compounds, including (+)-11b, within the AR ligand-binding domain have been studied by cocrystallization experiments using a coactivator-like peptide. Both compounds bound to the same site, and the overall structures of the AR were very similar.