5 - ( 4 - ( ( 1 3 S , 1 7 S ) - 3 , 1 7 - d i h y d r o x y - 1 3 - m e t h y l-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]-phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-N-(trityloxy)pentanamide | 1445868-61-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 5 - ( 4 - ( ( 1 3 S , 1 7 S ) - 3 , 1 7 - d i h y d r o x y - 1 3 - m e t h y l-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]-phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-N-(trityloxy)pentanamide
• 英文别名: 5-[4-[(8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,14,15,16-octahydro-6H-cyclopenta[a]phenanthren-17-yl]triazol-1-yl]-N-trityloxypentanamide
• CAS: 1445868-61-0
• 化学式: C₄₄H₄₈N₄O₄
• 分子量: 696.89
• InChiKey: XZHMBMPDNOLQCH-SRKGDLNLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  52
• 可旋转键数：
  11
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5 - ( 4 - ( ( 1 3 S , 1 7 S ) - 3 , 1 7 - d i h y d r o x y - 1 3 - m e t h y l-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]-phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-N-(trityloxy)pentanamide 在 三异丙基硅烷 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.34h， 以53.4%的产率得到5-(4-((8R,9S,13S,14S,17S)-3,17-dihydroxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-N-hydroxypentanamide
  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：

  5-azido-O-tritylpentahydroxamate 、 炔雌醇 在 copper(l) iodide 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 0.17h， 以90.8%的产率得到5 - ( 4 - ( ( 1 3 S , 1 7 S ) - 3 , 1 7 - d i h y d r o x y - 1 3 - m e t h y l-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]-phenanthren-17-yl)-1H-1,2,3-triazol-1-yl)-N-(trityloxy)pentanamide
  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