N-(8-Heptadecenyl)-3-hydroxypropionamide | 909891-91-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: N-(8-Heptadecenyl)-3-hydroxypropionamide
• 英文别名: N-(8Z)-8-Heptadecen-1-yl-3-hydroxypropanamide；N-[(Z)-heptadec-8-enyl]-3-hydroxypropanamide
• CAS: 909891-91-4
• 化学式: C₂₀H₃₉NO₂
• 分子量: 325.535
• InChiKey: MEHNYYNESVPJPE-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  23
• 可旋转键数：
  17
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  油酰氯 在 sodium azide 、 四丁基溴化铵 、 三甲基铝 作用下， 以 二氯甲烷 为溶剂， 生成 N-(8-Heptadecenyl)-3-hydroxypropionamide
  参考文献：
  名称：

  Pharmacological Characterization of Hydrolysis-Resistant Analogs of Oleoylethanolamide with Potent Anorexiant Properties

  摘要：

  油酰乙醇酰胺（OEA）是一种内源性脂质介质，可通过激活过氧化物酶体增殖激活受体-α（PPAR-α）来降低啮齿动物的食物摄入量、促进脂肪分解并减少体重增加。OEA 的生物效应由两种细胞内脂质水解酶（脂肪酸酰胺水解酶和 N -酰基乙醇胺水解酸酰胺酶）终止。在本研究中，我们描述了能抵抗酶水解的 OEA 类似物，它们能在体外高效力地激活 PPAR-α，并在体内经肠道或口服给药后持续减少摄食。这些化合物中效力最强的是 ( Z )-( R )-9- 十八烯酰胺，N -（2-羟乙基，1-甲基）（KDS-5104），它能刺激 PPAR-α 的转录活性，其半最大有效浓度（EC50）为 100 ± 21 nM（n = 11）。与 OEA 相比，KDS-5104 给大鼠肠外给药会产生持续的剂量依赖性进食潜伏期和餐后间隔延长（半数最大有效剂量，ED50 = 2.4 ± 1.8 mg kg-1 i.p.；n = 18），以及组织暴露增加和延长。在自由采食的大鼠中，口服该化合物也会导致显著的组织暴露和食物摄入量减少。这些结果表明，内源性高亲和力 PPAR-α 激动剂 OEA 可为发现新型口服活性 PPAR-α 配体提供支架。

  DOI：

  10.1124/jpet.106.105221

文献信息

• Compounds And Methods For Treating Non-Inflammatory Pain Using Ppar Alpha Agonists
  申请人：Piomelli Daniele

  公开号：US20080103209A1

  公开（公告）日：2008-05-01

  Compositions and methods for treating noninflammatory pain, including but not limited to, neuropathic pain by using peroxisome proliferator activated receptor a (PPARa) agonists to treat a subject having such pain are described. The agonists may be used with additional therapeutic agents such as an inhibitor of fatty acid amide hydrolase or a cannabinoid CB1 or CB2 cannabinoid receptor agonist.
• [EN] COMBINATION THERAPY FOR CONTROLLING APPETITES<br/>[FR] POLYTHÉRAPIE POUR CONTRÔLER L'APPÉTIT
  申请人：UNIV CALIFORNIA

  公开号：WO2004034968A2

  公开（公告）日：2004-04-29

  The invention provides methods and pharmaceutical compositions for administering a PPARα agonist (e.g., OEA-like agonist, OEA-like compound), an OEA-like appetite reducing compound, or a FAAH inhibitor and a CB1 cannabinoid receptor antagonist to a subject in order to reduce the consumption or ingestion of food, ethanol or other appetizing substances as well as in treating appetency disorders related to the excess consumption of food, ethanol, and other appetizing substances. The combination therapy can also be useful for reducing body fat or body weight and modulating lipid metabolism.
• Pharmacological Characterization of Hydrolysis-Resistant Analogs of Oleoylethanolamide with Potent Anorexiant Properties
  作者：Giuseppe Astarita、Barbara Di Giacomo、Silvana Gaetani、Fariba Oveisi、Timothy R. Compton、Silvia Rivara、Giorgio Tarzia、Marco Mor、Daniele Piomelli

  DOI：10.1124/jpet.106.105221

  日期：2006.8

  Oleoylethanolamide (OEA) is an endogenous lipid mediator that reduces food intake, promotes lipolysis, and decreases body weight gain in rodents by activating peroxisome proliferator-activated receptor-α (PPAR-α). The biological effects of OEA are terminated by two intracellular lipid hydrolase enzymes, fatty-acid amide hydrolase and N -acylethanolamine-hydrolyzing acid amidase. In the present study, we describe OEA analogs that resist enzymatic hydrolysis, activate PPAR-α with high potency in vitro, and persistently reduce feeding when administered in vivo either parenterally or orally. The most potent of these compounds, ( Z )-( R )-9-octadecenamide, N -(2-hydroxyethyl,1-methyl) (KDS-5104), stimulates transcriptional activity of PPAR-α with a half-maximal effective concentration (EC50) of 100 ± 21 nM ( n = 11). Parenteral administration of KDS-5104 in rats produces persistent dose-dependent prolongation of feeding latency and postmeal interval (half-maximal effective dose, ED50 = 2.4 ± 1.8 mg kg-1 i.p.; n = 18), as well as increased and protracted tissue exposure compared with OEA. Oral administration of the compound also results in a significant tissue exposure and reduction of food intake in free-feeding rats. These results suggest that the endogenous high-affinity PPAR-α agonist OEA may provide a scaffold for the discovery of novel orally active PPAR-α ligands.

  油酰乙醇酰胺（OEA）是一种内源性脂质介质，可通过激活过氧化物酶体增殖激活受体-α（PPAR-α）来降低啮齿动物的食物摄入量、促进脂肪分解并减少体重增加。OEA 的生物效应由两种细胞内脂质水解酶（脂肪酸酰胺水解酶和 N -酰基乙醇胺水解酸酰胺酶）终止。在本研究中，我们描述了能抵抗酶水解的 OEA 类似物，它们能在体外高效力地激活 PPAR-α，并在体内经肠道或口服给药后持续减少摄食。这些化合物中效力最强的是 ( Z )-( R )-9- 十八烯酰胺，N -（2-羟乙基，1-甲基）（KDS-5104），它能刺激 PPAR-α 的转录活性，其半最大有效浓度（EC50）为 100 ± 21 nM（n = 11）。与 OEA 相比，KDS-5104 给大鼠肠外给药会产生持续的剂量依赖性进食潜伏期和餐后间隔延长（半数最大有效剂量，ED50 = 2.4 ± 1.8 mg kg-1 i.p.；n = 18），以及组织暴露增加和延长。在自由采食的大鼠中，口服该化合物也会导致显著的组织暴露和食物摄入量减少。这些结果表明，内源性高亲和力 PPAR-α 激动剂 OEA 可为发现新型口服活性 PPAR-α 配体提供支架。