ethyl 6-[4-[4-[[2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]ethyl-methylamino]methyl]phenyl]triazol-1-yl]hexanoate | 1445868-73-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: ethyl 6-[4-[4-[[2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]ethyl-methylamino]methyl]phenyl]triazol-1-yl]hexanoate
• CAS: 1445868-73-4
• 化学式: C₄₂H₄₈N₄O₃
• 分子量: 656.868
• InChiKey: AVRAATGLYDGUIF-RUUVMHMZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.3
• 重原子数：
  49
• 可旋转键数：
  19
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  69.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 6-[4-[4-[[2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]ethyl-methylamino]methyl]phenyl]triazol-1-yl]hexanoate 在 potassium cyanide 、 羟胺 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 48.0h， 以100%的产率得到6-[4-[4-[[2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]ethyl-methylamino]methyl]phenyl]triazol-1-yl]-N-hydroxyhexanamide
  参考文献：
  名称：

  Histone Deacetylase Inhibitors Equipped with Estrogen Receptor Modulation Activity

  摘要：

  We describe a set of novel histone deacetylase inhibitors (HDACi) equipped with either an antagonist or an agonist of the estrogen receptor (ER) to confer selective activity against breast cancers. These bifunctional compounds potently inhibit HDAC at nanomolar concentrations and either agonize or antagonize ER alpha and ER beta. The ER antagonist activities of tamoxifen-HDACi conjugates (Tam-HDACi) are nearly identical to those of tamoxifen. Conversely, ethynyl-estradiol-HDACi conjugates (EED-HDACi) have attenuated ER agonist activities relative to the parent ethynyl-estradiol. In silico docking analysis provides structural basis for the trends of ER agonism/antagonism and ER subtype selectivity. Excitingly, lead Tam-HDACi conjugates show anticancer activity that is selectively more potent against MCF-7 (ER alpha positive breast cancer) compared to MDA-MB-231 (triple negative breast cancer), DU145 (prostate cancer), or Vero (noncancerous cell line). This dual-targeting approach illustrates the utility of designing small molecules with an emphasis on cell-type selectivity, not merely improved potency, working toward a higher therapeutic index at the earliest stages of drug development.

  DOI：

  10.1021/jm400467w
• 作为产物：
  描述：

  他莫昔芬 在 copper(l) iodide 、 1-氯乙基氯甲酸酯 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 二甲基亚砜 、 1,2-二氯乙烷 为溶剂， 反应 33.15h， 生成 ethyl 6-[4-[4-[[2-[4-[(Z)-1,2-diphenylbut-1-enyl]phenoxy]ethyl-methylamino]methyl]phenyl]triazol-1-yl]hexanoate
  参考文献：
  名称：

  Histone Deacetylase Inhibitors Equipped with Estrogen Receptor Modulation Activity

  摘要：

  We describe a set of novel histone deacetylase inhibitors (HDACi) equipped with either an antagonist or an agonist of the estrogen receptor (ER) to confer selective activity against breast cancers. These bifunctional compounds potently inhibit HDAC at nanomolar concentrations and either agonize or antagonize ER alpha and ER beta. The ER antagonist activities of tamoxifen-HDACi conjugates (Tam-HDACi) are nearly identical to those of tamoxifen. Conversely, ethynyl-estradiol-HDACi conjugates (EED-HDACi) have attenuated ER agonist activities relative to the parent ethynyl-estradiol. In silico docking analysis provides structural basis for the trends of ER agonism/antagonism and ER subtype selectivity. Excitingly, lead Tam-HDACi conjugates show anticancer activity that is selectively more potent against MCF-7 (ER alpha positive breast cancer) compared to MDA-MB-231 (triple negative breast cancer), DU145 (prostate cancer), or Vero (noncancerous cell line). This dual-targeting approach illustrates the utility of designing small molecules with an emphasis on cell-type selectivity, not merely improved potency, working toward a higher therapeutic index at the earliest stages of drug development.

  DOI：

  10.1021/jm400467w