4-[4-hydroxymethyl-4-(4-methoxyphenyl)-3-methyl-2,5-dioxo-imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile | 1401226-04-7

• 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-[4-hydroxymethyl-4-(4-methoxyphenyl)-3-methyl-2,5-dioxo-imidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
• 英文别名: 4-[4-(Hydroxymethyl)-4-(4-methoxyphenyl)-3-methyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile；4-[4-(hydroxymethyl)-4-(4-methoxyphenyl)-3-methyl-2,5-dioxoimidazolidin-1-yl]-2-(trifluoromethyl)benzonitrile
• CAS: 1401226-04-7
• 化学式: C₂₀H₁₆F₃N₃O₄
• 分子量: 419.36
• InChiKey: IRDRROXMWMWUSU-UHFFFAOYSA-N

物化性质

• 沸点：
  570.6±60.0 °C(predicted)
• 密度：
  1.49±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  93.9
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  4-溴-2-(三氟甲基)苯甲腈 在 copper(I) oxide 、 四(三苯基膦)钯 、 三正丁基氢锡 、 potassium carbonate 、 溶剂黄146 作用下， 以 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 23.5h， 生成 4-[4-hydroxymethyl-4-(4-methoxyphenyl)-3-methyl-2,5-dioxo-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

文献信息

• Identification of a 4-(Hydroxymethyl)diarylhydantoin as a Selective Androgen Receptor Modulator
  作者：François Nique、Séverine Hebbe、Nicolas Triballeau、Christophe Peixoto、Jean-Michel Lefrançois、Hélène Jary、Luke Alvey、Murielle Manioc、Christopher Housseman、Hugo Klaassen、Kris Van Beeck、Denis Guédin、Florence Namour、Dominque Minet、Ellen Van der Aar、Jean Feyen、Stephen Fletcher、Roland Blanqué、Catherine Robin-Jagerschmidt、Pierre Deprez

  DOI：10.1021/jm300281x

  日期：2012.10.11

  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.