4-[3-methyl-4-benzyloxymethyl-2,5-dioxo-4-(thiophen-3-yl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile | 1401225-99-7

• 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-methyl-4-benzyloxymethyl-2,5-dioxo-4-(thiophen-3-yl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
• 英文别名: 4-[3-Methyl-2,5-dioxo-4-(phenylmethoxymethyl)-4-thiophen-3-ylimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
• CAS: 1401225-99-7
• 化学式: C₂₄H₁₈F₃N₃O₃S
• 分子量: 485.486
• InChiKey: NEOLGPMOAHCBOP-UHFFFAOYSA-N

物化性质

• 沸点：
  601.9±65.0 °C(predicted)
• 密度：
  1.46±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  34
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  102
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-[3-methyl-4-benzyloxymethyl-2,5-dioxo-4-(thiophen-3-yl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile 在 10 wt% Pd(OH)2 on carbon 作用下， 以 乙醇 、 环己烯 为溶剂， 反应 3.0h， 以71%的产率得到4-(4-hydroxymethyl-3-methyl-2,5-dioxo-4-thiophen-3-yl-imidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Identification of a 4-(Hydroxymethyl)diarylhydantoin as a Selective Androgen Receptor Modulator

  摘要：

  Structural modification performed on a 4-methyl-4-(4-hydroxyphenyphyl)hydantoin series is described which resulted in the development of a new series of 4-(hydroxymethyl)diarylhydantoin analogues as potent, partial agonists of the human androgen receptor. This led to the identification of (S)-(-)-4-(4-(hydroxymethyl)-3-methyl-2,5-dioxo-4-phenylimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile ((S)-(-)-18a, GLPG0492) evaluated in vivo in a classical model of orchidectomized rat. In this model, (-)-18a exhibited anabolic activity on muscle, strongly dissociated from the androgenic activity on prostate after oral dosing. (-)-18a has very good pharmacokinetic properties, including bioavailability in rat (F > 50%), and is currently under evaluation in phase I clinical trials.

  DOI：

  10.1021/jm300281x
• 作为产物：
  描述：

  4-溴-2-(三氟甲基)苯甲腈 在 copper(I) oxide 、 potassium carbonate 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成 4-[3-methyl-4-benzyloxymethyl-2,5-dioxo-4-(thiophen-3-yl)imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
  参考文献：
  名称：

  Identification of a 4-(Hydroxymethyl)diarylhydantoin as a Selective Androgen Receptor Modulator

  摘要：

  Structural modification performed on a 4-methyl-4-(4-hydroxyphenyphyl)hydantoin series is described which resulted in the development of a new series of 4-(hydroxymethyl)diarylhydantoin analogues as potent, partial agonists of the human androgen receptor. This led to the identification of (S)-(-)-4-(4-(hydroxymethyl)-3-methyl-2,5-dioxo-4-phenylimidazolidin-1-yl)-2-(trifluoromethyl)benzonitrile ((S)-(-)-18a, GLPG0492) evaluated in vivo in a classical model of orchidectomized rat. In this model, (-)-18a exhibited anabolic activity on muscle, strongly dissociated from the androgenic activity on prostate after oral dosing. (-)-18a has very good pharmacokinetic properties, including bioavailability in rat (F > 50%), and is currently under evaluation in phase I clinical trials.

  DOI：

  10.1021/jm300281x