thiophosphoric acid O-tetradecyl ester

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫代磷酸及其衍生物
• 英文名称: thiophosphoric acid O-tetradecyl ester
• 英文别名: Thiophosphoric acid tetradecyl ester；dihydroxy-sulfanylidene-tetradecoxy-λ5-phosphane
• 化学式: C₁₄H₃₁O₃PS
• 分子量: 310.438
• InChiKey: BKCMZDGTQVOTOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  19
• 可旋转键数：
  14
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  十四醇 在 四氮唑 、 氢氧化钾 、 sulfur 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.5h， 生成 thiophosphoric acid O-tetradecyl 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

文献信息

• [EN] LPA RECEPTOR AGONISTS AND ANTAGONISTS<br/>[FR] AGONISTES DES RÉCEPTEURS DE LPA ET ANTAGONISTES
  申请人：RXBIO INC

  公开号：WO2010051053A1

  公开（公告）日：2010-05-06

  Disclosed are compounds according to formula (I) as well as pharmaceutical compositions which include those compounds. Also disclosed are methods of using such compounds, which have activity as agonists or as antagonists of LPA receptors; such methods including treating cancer, producing radioprotection and/or radiomitigation, enhancing cell proliferation, treating a wound, treating apoptosis or preserving or restoring function in a cell, tissue, or organ, culturing cells, preserving organ or tissue function, and treating a dermato logical condition.

  揭示了按照式(I)的化合物，以及包括这些化合物的药物组合物。还揭示了使用这些化合物的方法，这些方法具有作为LPA受体激动剂或拮抗剂的活性；这些方法包括治疗癌症、产生放射保护和/或减轻放射损伤、增强细胞增殖、治疗伤口、治疗凋亡或在细胞、组织或器官中保护或恢复功能、培养细胞、保护器官或组织功能，以及治疗皮肤病理条件。
• LPA receptor agonists and antagonists and methods of use
  申请人：Miller D. Duane

  公开号：US20060009507A1

  公开（公告）日：2006-01-12

  The present invention relates to compounds according to formula (I) as disclosed herein as well as pharmaceutical compositions which include those compounds. Also disclosed are methods of using such compounds, which have activity as agonists or as antagonists of LPA receptors; such methods including inhibiting LPA activity on an LPA receptor, modulating LPA receptor activity, treating cancer, enhancing cell proliferation, treating a wound, treating apoptosis or preserving or restoring function in a cell, tissue, or organ, culturing cells, preserving organ or tissue function, and treating a dermatological condition.

  本发明涉及公式（I）所示的化合物，以及包括这些化合物的制药组合物。还公开了使用这些化合物的方法，这些化合物具有作为LPA受体的激动剂或拮抗剂的活性；这些方法包括抑制LPA受体上的LPA活性，调节LPA受体活性，治疗癌症，增强细胞增殖，治疗伤口，治疗凋亡或在细胞、组织或器官中保持或恢复功能，培养细胞，保护器官或组织功能，以及治疗皮肤病症。
• LPA Receptor Agonists and Antagonists and Methods of Use
  申请人：Miller D. Duane

  公开号：US20080090783A1

  公开（公告）日：2008-04-17

  Disclosed are compounds according to formula (I) as well as pharmaceutical compositions which include those compounds. Also disclosed are methods of using such compounds, which have activity as agonists or as antagonists of LPA receptors; such methods including inhibiting LPA activity on an LPA receptor, modulating LPA receptor activity, treating cancer, enhancing cell proliferation, treating a wound, treating apoptosis or preserving or restoring function in a cell, tissue, or organ, culturing cells, preserving organ or tissue function, and treating a dermatological condition.

  本发明涉及化合物(I)及包含该化合物的药物组合物。还揭示了使用这些化合物的方法，这些方法具有作为LPA受体激动剂或拮抗剂的活性；这些方法包括抑制LPA受体上的LPA活性，调节LPA受体活性，治疗癌症，增强细胞增殖，治疗创伤，治疗凋亡或保护或恢复细胞、组织或器官的功能，培养细胞，保护器官或组织功能，以及治疗皮肤病症。
• LPA Receptor Agonists and Antagonists
  申请人：Gududuru Veeresh

  公开号：US20120010424A1

  公开（公告）日：2012-01-12

  Disclosed are compounds according to formula (I) as well as pharmaceutical compositions which include those compounds. Also disclosed are methods of using such compounds, which have activity as agonists or as antagonists of LPA receptors; such methods including treating cancer, producing radioprotection and/or radiomitigation, enhancing cell proliferation, treating a wound, treating apoptosis or preserving or restoring function in a cell, tissue, or organ, culturing cells, preserving organ or tissue function, and treating a dermato logical condition.

  本发明涉及公式（I）所示的化合物，以及包括这些化合物的制药组合物。本发明还涉及使用这些化合物的方法，这些化合物具有作为LPA受体的激动剂或拮抗剂的活性；这些方法包括治疗癌症、产生放射保护和/或减轻放射损伤、增强细胞增殖、治疗伤口、治疗凋亡或保护或恢复细胞、组织或器官的功能、培养细胞、保护器官或组织功能，以及治疗皮肤病症。
• LPA RECEPTOR AGONISTS AND ANTAGONISTS AND METHODS OF USE
  申请人：Miller Duane D.

  公开号：US20120135967A1

  公开（公告）日：2012-05-31

  Disclosed are compounds according to formula (I) as well as pharmaceutical compositions which include those compounds. Also disclosed are methods of using such compounds, which have activity as agonists or as antagonists of LPA receptors; such methods including inhibiting LPA activity on an LPA receptor, modulating LPA receptor activity, treating cancer, enhancing cell proliferation, treating a wound, treating apoptosis or preserving or restoring function in a cell, tissue, or organ, culturing cells, preserving organ or tissue function, and treating a dermatological condition.

  本发明公开了按照公式(I)的化合物，以及包括这些化合物的制药组合物。还公开了使用这些化合物的方法，这些化合物具有作为LPA受体的激动剂或拮抗剂的活性。这些方法包括抑制LPA在LPA受体上的活性，调节LPA受体活性，治疗癌症，增强细胞增殖，治疗伤口，治疗凋亡或保护或恢复细胞、组织或器官的功能，培养细胞，保护器官或组织功能以及治疗皮肤病条件。