4-{4-methyl-2,5-dioxo-4-[1-(toluene-4-sulfonyl)-1H-indol-5-yl]imidazolidin-1-yl}-2-(trifluoromethyl)benzonitrile | 1401224-87-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 英文名称: 4-{4-methyl-2,5-dioxo-4-[1-(toluene-4-sulfonyl)-1H-indol-5-yl]imidazolidin-1-yl}-2-(trifluoromethyl)benzonitrile
• 英文别名: 4-[4-Methyl-4-[1-(4-methylphenyl)sulfonylindol-5-yl]-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
• CAS: 1401224-87-0
• 化学式: C₂₇H₁₉F₃N₄O₄S
• 分子量: 552.533
• InChiKey: SCVBSFQVUMOFNG-UHFFFAOYSA-N

物化性质

• 密度：
  1.45±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  39
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  121
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-{4-methyl-2,5-dioxo-4-[1-(toluene-4-sulfonyl)-1H-indol-5-yl]imidazolidin-1-yl}-2-(trifluoromethyl)benzonitrile 在 sodium hydride 、 caesium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 27.5h， 生成 4-[4-(1H-indol-5-yl)-3,4-dimethyl-2,5-dioxoimidazolidin-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 、 5-methyl-5-[1-(toluene-4-sulfonyl)-1H-indol-5-yl]imidazolidine-2,4-dione 在 copper(I) oxide 作用下， 以 N,N-二甲基乙酰胺 为溶剂， 反应 18.0h， 以0.54 g的产率得到4-{4-methyl-2,5-dioxo-4-[1-(toluene-4-sulfonyl)-1H-indol-5-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