1-[(2S)-3-(2,4-dichlorophenoxy)-2-hydroxy-2-methylpropanoyl]-2,3-dihydroindole-4-carbonitrile | 1578263-73-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 1-[(2S)-3-(2,4-dichlorophenoxy)-2-hydroxy-2-methylpropanoyl]-2,3-dihydroindole-4-carbonitrile
• CAS: 1578263-73-6
• 化学式: C₁₉H₁₆Cl₂N₂O₃
• 分子量: 391.254
• InChiKey: OPSKHUQVAQWGKY-IBGZPJMESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  73.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  4-溴吲哚 在 sodium cyanoborohydride 、 potassium carbonate 、 溶剂黄146 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基乙酰胺 、 N,N-二甲基甲酰胺 、 丁酮 为溶剂， 反应 93.0h， 生成 1-[(2S)-3-(2,4-dichlorophenoxy)-2-hydroxy-2-methylpropanoyl]-2,3-dihydroindole-4-carbonitrile
  参考文献：
  名称：

  1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators

  摘要：

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.

  DOI：

  10.1021/jm401625b

文献信息

• 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)indoline-4-carbonitrile Derivatives as Potent and Tissue Selective Androgen Receptor Modulators
  作者：Eugene L. Piatnitski Chekler、Rayomond Unwalla、Taukeer A. Khan、Raghuram S. Tangirala、Mark Johnson、Michael St. Andre、James T. Anderson、Thomas Kenney、Sue Chiparri、Chris McNally、Edward Kilbourne、Catherine Thompson、Sunil Nagpal、Gregory Weber、Scott Schelling、Jane Owens、Carl A. Morris、Dennis Powell、Patrick R. Verhoest、Adam M. Gilbert

  DOI：10.1021/jm401625b

  日期：2014.3.27

  We present a novel series of selective androgen receptor modulators (SARMs) which shows excellent biological activity and physical properties. 1-(2-Hydroxy-2-methyl-3-phenoxypropanoyl)-indoline-4-carbonitriles showed potent binding to the androgen receptor (AR) and activated AR-mediated transcription in vitro. Representative compounds demonstrated diminished activity in promoting the intramolecular interaction between the AR carboxyl (C) and amino (N) termini. This N/C-termini interaction is a biomarker assay for the undesired androgenic responses in vivo. In orchidectomized rats, daily administration of a lead compound from this series showed anabolic activity by increasing levator ani muscle weight. Importantly, minimal androgenic effects (increased tissue weights) were observed in the prostate and seminal vesicles, along with minimal repression of circulating luteinizing hormone (LH) levels and no change in the lipid and triglyceride levels. This lead compound completed a two week rat toxicology study, and was well tolerated at doses up to 100 mg/kg/day, the highest dose tested, for 14 consecutive days.