niphatenone B | 1354382-50-5

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 甘油脂
• 英文名称: niphatenone B
• 英文别名: (E)-1-[(2S)-2,3-dihydroxypropoxy]octadec-4-en-6-one
• CAS: 1354382-50-5
• 化学式: C₂₁H₄₀O₄
• 分子量: 356.546
• InChiKey: UJRKZHMKHFVGBP-WMJZSHNHSA-N

物化性质

• 沸点：
  511.5±50.0 °C(Predicted)
• 密度：
  0.969±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  25
• 可旋转键数：
  19
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  66.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,2-环氧十四烷 在 盐酸 、 cerium(III) chloride heptahydrate 、 水 、 戴斯-马丁氧化剂 、 sodium bromide 、 barium(II) hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 51.0h， 生成 niphatenone B
  参考文献：
  名称：

  Niphatenones, Glycerol Ethers from the Sponge Niphates digitalis Block Androgen Receptor Transcriptional Activity in Prostate Cancer Cells: Structure Elucidation, Synthesis, and Biological Activity

  摘要：

  Extracts of the marine sponge Niphates digitalis collected in Dominica showed strong activity in a cell-based assay designed to detect antagonists of the androgen receptor (AR) that could act as lead compounds for the development of a new class of drugs to treat castration recurrent prostate cancer (CRPC). Assay-guided fractionation showed that niphatenones A (3) and B (4), two new glycerol ether lipids, were the active components of the extracts. The structures of 3 and 4 were elucidated by analysis of NMR and MS data and confimed via total synthesis. Biological evaluation of synthetic analogues of the niphatenones has shown that the enantiomers 7 and 8 are more potent than the natural products in the screening assay and defined preliminary SAR for the new AR antagonist pharmacophore, including the finding that the Michael acceptor enone functionality is not required for activity. Niphatenone B (4) and its enantiomer 8 blocked androgen-induced proliferation of LNCaP prostate cancer cells but had no effect on the proliferation of PC3 prostate cancer cells that do not express functional AR, consistent with activity as AR antagonists. Use of the propargyl ether 44 and Click chemistry showed that niphatenone B binds covalently to the activation function-1 (AF1) region of the AR N-terminus domain (NTD).

  DOI：

  10.1021/jm2014056

文献信息

• Niphatenones, Glycerol Ethers from the Sponge <i>Niphates digitalis</i> Block Androgen Receptor Transcriptional Activity in Prostate Cancer Cells: Structure Elucidation, Synthesis, and Biological Activity
  作者：Labros G. Meimetis、David E. Williams、Nasrin R. Mawji、Carmen A. Banuelos、Aaron A. Lal、Jacob J. Park、Amy H. Tien、Javier Garcia Fernandez、Nicole J. de Voogd、Marianne D. Sadar、Raymond J. Andersen

  DOI：10.1021/jm2014056

  日期：2012.1.12

  Extracts of the marine sponge Niphates digitalis collected in Dominica showed strong activity in a cell-based assay designed to detect antagonists of the androgen receptor (AR) that could act as lead compounds for the development of a new class of drugs to treat castration recurrent prostate cancer (CRPC). Assay-guided fractionation showed that niphatenones A (3) and B (4), two new glycerol ether lipids, were the active components of the extracts. The structures of 3 and 4 were elucidated by analysis of NMR and MS data and confimed via total synthesis. Biological evaluation of synthetic analogues of the niphatenones has shown that the enantiomers 7 and 8 are more potent than the natural products in the screening assay and defined preliminary SAR for the new AR antagonist pharmacophore, including the finding that the Michael acceptor enone functionality is not required for activity. Niphatenone B (4) and its enantiomer 8 blocked androgen-induced proliferation of LNCaP prostate cancer cells but had no effect on the proliferation of PC3 prostate cancer cells that do not express functional AR, consistent with activity as AR antagonists. Use of the propargyl ether 44 and Click chemistry showed that niphatenone B binds covalently to the activation function-1 (AF1) region of the AR N-terminus domain (NTD).