phosphoric acid di-tert-butyl ester octadec-9-enyl ester | 849721-41-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机磷酸及其衍生物
• 英文名称: phosphoric acid di-tert-butyl ester octadec-9-enyl ester
• 英文别名: Ditert-butyl octadec-9-enyl phosphate
• CAS: 849721-41-1
• 化学式: C₂₆H₅₃O₄P
• 分子量: 460.678
• InChiKey: YCJKLLDANAQKLU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  9.4
• 重原子数：
  31
• 可旋转键数：
  21
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  phosphoric acid di-tert-butyl ester octadec-9-enyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以86%的产率得到磷酸二氢-9-十八烯-1-醇酯
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Biological Evaluation of Fatty Alcohol Phosphates as Lysophosphatidic Acid Receptor Ligands, Activators of PPARγ, and Inhibitors of Autotaxin

  摘要：

  We previously reported that fatty alcohol phosphates (FAP) represent a minimal pharmacophore required to interact with lysophosphatidic acid (LPA) receptors. To improve the activity of the first-generation saturated FAP series, a structure-activity relationship (SAR) study was carried out that includes modifications to the headgroup and alkyl side chain of the FAP pharmacophore. A series of unsaturated (C-10-C-18) FAP, headgroup-modified hydrolytically stable saturated (C-10-C-18) alkyl phosphonates, and saturated and unsaturated (C-10-C-18) thiophosphate analogues were synthesized and evaluated for activity in RH7777 cells transfected with individual LPA(1-3) receptors, in PC-3 cells and in human platelets that endogenously express all three isoforms. In this series we identified several LPA(1)- and LPA(3)-selective antagonists with IC50 values in the nanomolar range. Oleoyl-thiophosphate (15g) was shown to be a panagonist, whereas tetradecyl-phosphonate (16c) was identified as a pan-antagonist. These compounds were also tested for the ability to activate the transcription factor PPAR gamma, an intracellular receptor for LPA, in CV1 cells transfected with the PPRE-Acox-Rluc reporter gene. All the FA-P tested, along with the previously reported LPA GPCR antagonists dioctanoyl glycerol pyrophosphate (2), Ki16425 (6), and the agonist OMPT (3), were activators of PPAR gamma. The pan-agonist oleoyl-thiophosphate (15g) and pan-antagonist tetradecyl-phosphonate (16c) mimicked LPA in inhibiting autotaxin, a secreted lysophospholipase D that produces LPA in biological fluids.

  DOI：

  10.1021/jm049609r
• 作为产物：
  描述：

  油醇 在 四氮唑 、 双氧水 作用下， 以 二氯甲烷 为溶剂， 反应 1.5h， 生成 phosphoric acid di-tert-butyl ester octadec-9-enyl ester
  参考文献：
  名称：

  Synthesis, Structure−Activity Relationships, and Biological Evaluation of Fatty Alcohol Phosphates as Lysophosphatidic Acid Receptor Ligands, Activators of PPARγ, and Inhibitors of Autotaxin

  摘要：

  We previously reported that fatty alcohol phosphates (FAP) represent a minimal pharmacophore required to interact with lysophosphatidic acid (LPA) receptors. To improve the activity of the first-generation saturated FAP series, a structure-activity relationship (SAR) study was carried out that includes modifications to the headgroup and alkyl side chain of the FAP pharmacophore. A series of unsaturated (C-10-C-18) FAP, headgroup-modified hydrolytically stable saturated (C-10-C-18) alkyl phosphonates, and saturated and unsaturated (C-10-C-18) thiophosphate analogues were synthesized and evaluated for activity in RH7777 cells transfected with individual LPA(1-3) receptors, in PC-3 cells and in human platelets that endogenously express all three isoforms. In this series we identified several LPA(1)- and LPA(3)-selective antagonists with IC50 values in the nanomolar range. Oleoyl-thiophosphate (15g) was shown to be a panagonist, whereas tetradecyl-phosphonate (16c) was identified as a pan-antagonist. These compounds were also tested for the ability to activate the transcription factor PPAR gamma, an intracellular receptor for LPA, in CV1 cells transfected with the PPRE-Acox-Rluc reporter gene. All the FA-P tested, along with the previously reported LPA GPCR antagonists dioctanoyl glycerol pyrophosphate (2), Ki16425 (6), and the agonist OMPT (3), were activators of PPAR gamma. The pan-agonist oleoyl-thiophosphate (15g) and pan-antagonist tetradecyl-phosphonate (16c) mimicked LPA in inhibiting autotaxin, a secreted lysophospholipase D that produces LPA in biological fluids.

  DOI：

  10.1021/jm049609r