4-[[(2S,4S)-4-benzyl-2-tert-butyl-5-oxo-1,3-dioxolan-4-yl]methoxy]benzonitrile | 1250441-07-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 4-[[(2S,4S)-4-benzyl-2-tert-butyl-5-oxo-1,3-dioxolan-4-yl]methoxy]benzonitrile
• CAS: 1250441-07-6
• 化学式: C₂₂H₂₃NO₄
• 分子量: 365.429
• InChiKey: PQFSBEOCMPFOSA-IRLDBZIGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4-[[(2S,4S)-4-benzyl-2-tert-butyl-5-oxo-1,3-dioxolan-4-yl]methoxy]benzonitrile 在 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 生成 (2S)-2-benzyl-3-(4-cyanophenoxy)-N-[4-cyano-3-(trifluoromethyl)phenyl]-2-hydroxypropanamide
  参考文献：
  名称：

  A New Avenue toward Androgen Receptor Pan-antagonists: C2 Sterically Hindered Substitution of Hydroxy-propanamides

  摘要：

  The androgen receptor (AR) represents the primary target for prostate cancer (PC) treatment even when the disease progresses toward androgen-independent (AIPC) or castration-resistant (CRPC) forms. Because small chemical changes in the structure of nonsteroidal AR ligands determine the pharmacological responses of AR, we developed a novel stereoselective synthetic strategy that allows sterically hindered C2-substituted bicalutamide analogues to be obtained. Biological and theoretical evaluations demonstrate that C2-substitution with benzyl and phenyl moieties is a new, valuable option toward improving pan-antagonist behavior. Among the synthesized compounds, (R)-16m, when compared to casodex, (R)-bicalutamide, and enzalutamide, displayed very promising in vitro activity toward five different prostate cancer cell lines, all representative of CPRC and AIPC typical mutations. Despite being less active than (R)-bicalutamide, (R)-16m also displayed marked in vivo antitumor activity on VCaP xenografts and thus it may serve as starting point for developing novel AR pan-antagonists.

  DOI：

  10.1021/jm5005122
• 作为产物：
  描述：

  溴甲苯 在 三氯溴甲烷 、 potassium carbonate 、 N,N'-二环己基碳二亚胺 、 lithium hexamethyldisilazane 、 2-巯基吡啶-N-氧化物 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.5h， 生成 4-[[(2S,4S)-4-benzyl-2-tert-butyl-5-oxo-1,3-dioxolan-4-yl]methoxy]benzonitrile
  参考文献：
  名称：

  A New Avenue toward Androgen Receptor Pan-antagonists: C2 Sterically Hindered Substitution of Hydroxy-propanamides

  摘要：

  The androgen receptor (AR) represents the primary target for prostate cancer (PC) treatment even when the disease progresses toward androgen-independent (AIPC) or castration-resistant (CRPC) forms. Because small chemical changes in the structure of nonsteroidal AR ligands determine the pharmacological responses of AR, we developed a novel stereoselective synthetic strategy that allows sterically hindered C2-substituted bicalutamide analogues to be obtained. Biological and theoretical evaluations demonstrate that C2-substitution with benzyl and phenyl moieties is a new, valuable option toward improving pan-antagonist behavior. Among the synthesized compounds, (R)-16m, when compared to casodex, (R)-bicalutamide, and enzalutamide, displayed very promising in vitro activity toward five different prostate cancer cell lines, all representative of CPRC and AIPC typical mutations. Despite being less active than (R)-bicalutamide, (R)-16m also displayed marked in vivo antitumor activity on VCaP xenografts and thus it may serve as starting point for developing novel AR pan-antagonists.

  DOI：

  10.1021/jm5005122

文献信息

• NON-STEROIDAL COMPOUNDS FOR ANDROGEN RECEPTOR MODULATION
  申请人：Varchi Greta

  公开号：US20120041046A1

  公开（公告）日：2012-02-16

  The present invention concerns compounds of general Formula (I): method of preparation and uses thereof.
• US8741951B2
  申请人：——

  公开号：US8741951B2

  公开（公告）日：2014-06-03