N-(3-hydroxypropyl)-Oleamide | 26021-22-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: N-(3-hydroxypropyl)-Oleamide
• 英文别名: N-(3-Hydroxypropyl)oleamide；(Z)-N-(3-hydroxypropyl)octadec-9-enamide
• CAS: 26021-22-7
• 化学式: C₂₁H₄₁NO₂
• 分子量: 339.562
• InChiKey: UDZJZDBQGJPVOQ-KTKRTIGZSA-N

物化性质

• 沸点：
  510.5±43.0 °C(Predicted)
• 密度：
  0.912±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  6.7
• 重原子数：
  24
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N-(3-hydroxypropyl)-Oleamide 在 pyridinium chlorochromate 作用下， 以47%的产率得到(9Z)-N-(3-oxopropyl)Octadec-9-enamide
  参考文献：
  名称：

  溶血磷脂酸的膦酸和硫代磷酸衍生物的合成及生物学评价。

  摘要：

  使用N-油酰基乙醇酰胺支架，制备了由各种α-取代的膦酸酯和硫代磷酸酯组成的一系列LPA的磷酸极性头基类似物。在破碎的细胞GTP [γ35S]结合试验中，对内皮分化基因（Edg）家族的三个LPA受体的激动剂活性进行了评估。这项研究导致发现了一种不可水解的LPA1选择性激动剂（11）。另外，硫代磷酸盐19带有等位磷酸酯模拟物，其赋予LPA1受体而非LPA2激动作用。

  DOI：

  10.1016/j.bmcl.2004.04.061
• 作为产物：
  描述：

  octadecanoic acid (3-trimethylsilanyloxypropyl)amide 在 盐酸 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以93%的产率得到N-(3-hydroxypropyl)-Oleamide
  参考文献：
  名称：

  Lysophosphatidic acid signaling via LPA ₆ : A negative modulator of developmental oligodendrocyte maturation

  摘要：

  AbstractThe developmental process of central nervous system (CNS) myelin sheath formation is characterized by well‐coordinated cellular activities ultimately ensuring rapid and synchronized neural communication. During this process, myelinating CNS cells, namely oligodendrocytes (OLGs), undergo distinct steps of differentiation, whereby the progression of earlier maturation stages of OLGs represents a critical step toward the timely establishment of myelinated axonal circuits. Given the complexity of functional integration, it is not surprising that OLG maturation is controlled by a yet fully to be defined set of both negative and positive modulators. In this context, we provide here first evidence for a role of lysophosphatidic acid (LPA) signaling via the G protein‐coupled receptor LPA6 as a negative modulatory regulator of myelination‐associated gene expression in OLGs. More specifically, the cell surface accessibility of LPA6 was found to be restricted to the earlier maturation stages of differentiating OLGs, and OLG maturation was found to occur precociously in Lpar6 knockout mice. To further substantiate these findings, a novel small molecule ligand with selectivity for preferentially LPA6 and LPA6 agonist characteristics was functionally characterized in vitro in primary cultures of rat OLGs and in vivo in the developing zebrafish. Utilizing this approach, a negative modulatory role of LPA6 signaling in OLG maturation could be corroborated. During development, such a functional role of LPA6 signaling likely serves to ensure timely coordination of circuit formation and myelination. Under pathological conditions as seen in the major human demyelinating disease multiple sclerosis (MS), however, persistent LPA6 expression and signaling in OLGs can be seen as an inhibitor of myelin repair. Thus, it is of interest that LPA6 protein levels appear elevated in MS brain samples, thereby suggesting that LPA6 signaling may represent a potential new druggable pathway suitable to promote myelin repair in MS.image

  DOI：

  10.1111/jnc.15696

文献信息

• Structure/Activity Relationships in Lysophosphatidic Acid: The 2-Hydroxyl Moiety
  作者：Kevin R. Lynch、Darrin W. Hopper、Steven J. Carlisle、John G. Catalano、Ming Zhang、Timothy L. Macdonald

  DOI：10.1124/mol.52.1.75

  日期：1997.7.1

  Although lipid phosphoric acid mediators such as lysophosphatidic acid (LPA) are now recognized widely as intercellular signaling molecules, the medicinal chemistry of these mediators is poorly developed. With the goal of achieving a better understanding of the structure activity relationships in LPA, we have synthesized and tested a series of LPA analogs that lack the 2-hydroxyl moiety. Our series consisted of compounds with 2, 3, or 4 carbon diol or amino alcohol backbones and oleoyl or palmitoleoyl acyl groups. These molecules cannot be acylated further to form phosphatidic acids, nor do they have chiral centers. The rank order potency of these compounds in mobilization of calcium in MDA MB-231 cells suggested a maximum optimal chain length of 24–25 atoms. However, high potency for the inhibition of adenylyl cyclase in these cells was achieved only by one compound that also contained a dissociable proton five bond lengths from the phosphorus atom. That compound, N -oleoyl-2-hydroxyethyl-1-phosphate, was nearly equipotent to 1-oleoyl LPA in both assays. The striking mimicry of LPA by the ethanolamine-based compound and the presence of fatty acid amides in tissue prompts us to propose that phosphorylated N -acyl ethanolamides occur naturally.

  尽管脂磷酸类介质如溶血磷脂酸（LPA）现已被广泛认可为细胞间信号分子，但这些介质的药物化学研究尚处于起步阶段。为了更好地理解LPA结构活性关系，我们合成并测试了一系列缺乏2-羟基部分的LPA类似物。我们的研究系列包括具有2、3或4个碳的二醇或氨基醇骨架以及油酰或棕榈油酰酰基的化合物。这些分子不能进一步酰化形成磷脂酸，也不具有手性中心。这些化合物在MDA MB-231细胞中动员钙的活性排序提示了最大最佳链长度为24-25个原子。然而，在这些细胞中抑制腺苷酸环化酶的高效活性仅由一种化合物实现，该化合物在磷原子五键长度处含有一个可解离的质子。该化合物，即N-油酰-2-羟乙基-1-磷酸，在两种检测中与1-油酰LPA几乎等效。基于这种以乙醇胺为基础的化合物对LPA的惊人模拟及组织中脂肪酸酰胺的存在，我们推测自然界中存在磷酸化的N-酰基乙醇酰胺。
• Compositions containing lysophosphotidic acids which inhibit apoptosis and uses thereof
  申请人：Sky High, LLC

  公开号：US06495532B1

  公开（公告）日：2002-12-17

  The present invention provides therapeutic compositions containing lysophosphotidic acids, methods for making the compositions, and methods of using the compositions in the preservation and treatment of organs.

  本发明提供了含有溶血磷脂酸的治疗组合物、制备该组合物的方法，以及在器官的保存和治疗中使用该组合物的方法。
• Compositions containing lysophosphatidic acids which inhibit apoptosis and uses thereof
  申请人：Goddard John G.

  公开号：US06949528B1

  公开（公告）日：2005-09-27

  The invention provides anti-apoptotic compositions lysophosphatidic acids and methods for making and using the compositions. Such compositions can also contain LPA potentiating agents, including proteins, lipid membrane structures and polymers such as polyethylene glycols. The compositions can additionally contain other pharmaceutically effective agents such as drugs, antibiotics, wound healing agents and antioxidants.

  该发明提供了抗凋亡组合物溶磷脂酸及其制备和使用方法。这种组合物还可以包含增强LPA作用的剂，包括蛋白质、脂质膜结构和聚合物，如聚乙二醇。该组合物还可以额外含有其他药用有效剂，如药物、抗生素、伤口愈合剂和抗氧化剂。
• Facile synthesis of lysophospholipids containing unsaturated fatty acid chains
  作者：Darrin W. Hopper、John G. Catalano、Timothy L. Macdonald

  DOI：10.1016/0040-4039(96)01802-3

  日期：1996.10

  The efficient synthesis of polyunsaturated phospholipids is challenging due to the sensitivity of the unsaturated moiety to the conditions employed in phosphate ester deprotection. We discuss here three independent methods that resolve this issue and enable the synthesis of a series of unsaturated lysophosphatidic acid mimics for the development of a more comprehensive understanding of the structure-activity

  由于不饱和部分对磷酸酯脱保护中所用条件的敏感性，有效合成多不饱和磷脂具有挑战性。我们在这里讨论三种独立的方法来解决此问题，并使一系列不饱和溶血磷脂酸模拟物的合成，以发展对该系列中结构-活性关系的更全面的了解。
• Novel lysophosphatidic acid receptor agonists and antagonists
  申请人：——

  公开号：US20040122236A1

  公开（公告）日：2004-06-24

  The present invention is directed to compositions comprising lysophosphatidic acid analogs and methods of using such analogs as agonist or antagonists of LPA receptor activity. In addition the invention is directed to LPA receptor agonists that vary in the degree of selectivity at individual LPA receptors (i.e. LPA1, LPA2 and LPA3). More particularly the present invention is directed to LPA analogs wherein the glycerol is replaced with ethanolamine and a variety of substitutions have been linked at the second carbon atom.

  本发明涉及包含溶血磷脂酸类似物的组合物，并使用这些类似物作为LPA受体活性的激动剂或拮抗剂的方法。此外，本发明涉及在个体LPA受体（即LPA1，LPA2和LPA3）上选择性程度不同的LPA受体激动剂。更具体地，本发明涉及LPA类似物，其中甘油被乙醇胺替换，并且在第二个碳原子上连接了各种取代基。