N-(2-羟基-1r-甲基乙基)-十六酰胺 | 142128-47-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: N-(2-羟基-1r-甲基乙基)-十六酰胺
• 英文名称: (R)-N-(2-hydroxy-1-methylethyl)hexadecanamide
• 英文别名: (R)-palmitoyl(1-methylethanolamide)；(R)-N-(1-hydroxypropan-2-yl)palmitamide；N-[(1R)-2-hydroxy-1-methylethyl]-hexadecanamide；N-[(2R)-1-Hydroxypropan-2-yl]hexadecanamide
• CAS: 142128-47-0
• 化学式: C₁₉H₃₉NO₂
• 分子量: 313.524
• InChiKey: RYVPKPNOVYCJAP-GOSISDBHSA-N

物化性质

• 溶解度：
  乙醇中≤10mg/ml；DMSO 中≤25mg/ml；二甲基甲酰胺中≤3.3mg/ml

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  22
• 可旋转键数：
  16
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.95
• 拓扑面积：
  49.3
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2924199090
• 储存条件：
  -20°C，密闭保存，置于干燥处。

制备方法与用途

R-棕榈酰-(1-甲基)乙醇胺是一种合成的PEA类似物，在乙醇胺部分邻近醇羟基的位置引入了一个(R)-甲基。

反应信息

• 作为反应物：
  描述：

  N-(2-羟基-1r-甲基乙基)-十六酰胺 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 乙腈 、 苯 为溶剂， 反应 18.0h， 生成 (R)-O-(2-hexadecanamidopropyl)phosphocholine
  参考文献：
  名称：

  设计和合成了一些磷脂酶A2的底物类似物抑制剂，并通过NMR和分子建模研究了酶抑制剂复合物中的结合相互作用。

  摘要：

  已经设计和合成了一系列胰磷脂酶A2的底物类似物抑制剂。在基于单体和胶束底物平行测定的新型双重筛选系统中对化合物进行了测试。在酶抑制剂复合物的溶液NMR研究中已观察到一种质子在一种抑制剂上的乙烯基质子与牛胰腺酶上已确定的活性位点残基之间的分子间核Overhauser效应。从生化结果和NMR数据都可以推论，这种抑制剂与磷脂酶A2的活性位点之间的相互作用方式基本上是相同的，而不管是否存在聚集的磷脂表面。已开发出结合了二维NMR数据的酶与抑制剂之间结合的模型。

  DOI：

  10.1021/jm00094a003
• 作为产物：
  描述：

  D-氨基丙醇 、 棕榈酸甲酯 反应 5.0h， 生成 N-(2-羟基-1r-甲基乙基)-十六酰胺
  参考文献：
  名称：

  COMPOSITIONS AND METHODS FOR THE MODULATION OF SPECIFIC AMIDASES FOR N-ACYLETHANOLAMINES FOR USE IN THE THERAPY OF INFLAMMATORY DISEASES

  摘要：

  本发明涉及用于调节能够水解N-酰乙醇胺的酰胺酶的组合物和方法，用于治疗炎症性疾病。具体来说，本发明涉及一般式(I)的化合物：对映体、非对映异构体、消旋体和混合物、多形态、盐、溶剂化合物，其中：(a) R是具有13至19个碳原子的直链烷基基团或具有13至19个碳原子并带有一个双键的烯基基团；(b) X为0或S；(c) Y为2或3个碳原子的烷基烃基残基，可选择地取代一个或两个相等或不同的基团，所述基团选自以下群组中的一种：—CH3、—CH2OH、—COOCH3、—COOH。Y可能更倾向于是：—CH2—CH2—、—CH2—CH2—CH2—、CH(CH3)—CH2—、—CH2—CH(CH3)—、—CH2—C(CH3)2—、—CH2—CH(CH2OH)—、—CH2—C((CH2OH)2—、—CH═CH—、—CH2—CH(COOCH3)—、—CH2—CH(COOH)—，用作药物。

  公开号：

  US20150057269A1

文献信息

• Amino Acid Derivatives as Palmitoylethanolamide Prodrugs: Synthesis, In Vitro Metabolism and In Vivo Plasma Profile in Rats
  作者：Federica Vacondio、Michele Bassi、Claudia Silva、Riccardo Castelli、Caterina Carmi、Laura Scalvini、Alessio Lodola、Valentina Vivo、Lisa Flammini、Elisabetta Barocelli、Marco Mor、Silvia Rivara

  DOI：10.1371/journal.pone.0128699

  日期：——

  Palmitoylethanolamide (PEA) has antinflammatory and antinociceptive properties widely exploited in veterinary and human medicine, despite its poor pharmacokinetics. Looking for prodrugs that could progressively release PEA to maintain effective plasma concentrations, we prepared carbonates, esters and carbamates at the hydroxyl group of PEA. Chemical stability (pH 7.4) and stability in rat plasma and liver homogenate were evaluated by in vitro assays. Carbonates and carbamates resulted too labile and too resistant in plasma, respectively. Ester derivatives, prepared by conjugating PEA with various amino acids, allowed to modulate the kinetics of PEA release in plasma and stability in liver homogenate. L-Val-PEA, with suitable PEA release in plasma, and D-Val-PEA, with high resistance to hepatic degradation, were orally administered to rats and plasma levels of prodrugs and PEA were measured at different time points. Both prodrugs showed significant release of PEA, but provided lower plasma concentrations than those obtained with equimolar doses of PEA. Amino-acid esters of PEA are a promising class to develop prodrugs, even if they need further chemical optimization.

  棕榈酰乙醇胺（PEA）具有抗炎和镇痛特性，在兽医和人类医学中得到广泛应用，尽管其药代动力学特性不佳。为了寻找能够逐步释放PEA以维持有效血浆浓度的前药，我们制备了在PEA的羟基上的碳酸盐、酯和氨基甲酸酯。通过体外试验评估了这些化合物的化学稳定性（pH 7.4）以及在鼠血浆和肝匀浆中的稳定性。碳酸盐和氨基甲酸酯在血浆中分别表现出过于不稳定和过于稳定。通过将PEA与各种氨基酸结合制备的酯衍生物，能够在血浆中调节PEA的释放动力学并在肝匀浆中稳定存在。L-Val-PEA在血浆中具有适当的PEA释放，而D-Val-PEA对肝脏降解具有较高的抵抗性，两者均通过口服给予大鼠，并在不同时间点测量了血浆中前药和PEA的水平。两种前药均显示了显著的PEA释放，但提供的血浆浓度低于等摩尔剂量的PEA。PEA的氨基酸酯类是一类有前景的前药开发类别，尽管它们需要进一步的化学优化。
• Different roles for the acyl chain and the amine leaving group in the substrate selectivity of <i>N</i>-Acylethanolamine acid amidase
  作者：Andrea Ghidini、Laura Scalvini、Francesca Palese、Alessio Lodola、Marco Mor、Daniele Piomelli

  DOI：10.1080/14756366.2021.1912035

  日期：2021.1.1

  length is still lacking. In this report, we combined enzymatic and molecular modelling approaches to determine the effects of acyl chain and polar head modifications on substrate recognition and hydrolysis by NAAA. The results show that, in both saturated and monounsaturated FAEs, the catalytic efficiency is strictly dependent upon fatty acyl chain length, whereas there is a wider tolerance for modifications

  摘要 N-酰基乙醇胺酸酰胺酶 (NAAA) 是一种N-末端亲核试剂 (Ntn) 水解酶催化内源性镇痛和抗炎剂棕榈酰乙醇酰胺 (PEA) 的细胞内失活。NAAA 抑制剂可以抵消这一过程，并在疼痛、炎症和神经退行性疾病的动物模型中发挥显着的治疗作用。虽然已知 NAAA 优先水解饱和脂肪酸乙醇酰胺 (FAE)，但仍缺乏催化效率与脂肪酸链长度之间关系的详细概况。在本报告中，我们结合酶促和分子建模方法来确定酰基链和极性头部修饰对 NAAA 底物识别和水解的影响。结果表明，在饱和和单不饱和 FAE 中，催化效率严格取决于脂肪酰基链长，而对极头的修改有更广泛的容忍度。这种关系反映了酶-底物复合物在分子动力学模拟中的相对稳定性。
• [EN] COMPOSITIONS AND METHODS FOR THE MODULATION OF SPECIFIC AMIDASES FOR N-ACYLETHANOLAMINES FOR USE IN THE THERAPY OF INFLAMMATORY DISEASES<br/>[FR] COMPOSITIONS ET PROCÉDÉS POUR LA MODULATION D'AMIDASES SPÉCIFIQUES POUR DES N-ACYLÉTHANOLAMINES EN VUE D'UNE UTILISATION DANS LA THÉRAPIE CONTRE LES MALADIES INFLAMMATOIRES
  申请人：EPITECH GROUP SRL

  公开号：WO2013121449A8

  公开（公告）日：2013-12-12
• Evaluation of endogenous fatty acid amides and their synthetic analogues as potential anti-inflammatory leads
  作者：Hung The Dang、Gyeoung Jin Kang、Eun Sook Yoo、Jongki Hong、Jae Sue Choi、Hyung Sik Kim、Hae Young Chung、Jee H. Jung

  DOI：10.1016/j.bmc.2010.12.046

  日期：2011.2

  A series of endogenous fatty acid amides and their analogues (1-78) were prepared, and their inhibitory effects on pro-inflammatory mediators (NO, IL-1 beta, IL-6, and TNF-alpha) in LPS-activated RAW264.7 cells were evaluated. Their inhibitory activity on the pro-inflammatory chemokine MDC in IFN-gamma-activated HaCaT cells was also examined. The results showed that the activity is strongly dependent on the nature of the fatty acid part of the molecules. As expected, the amides derived from enone fatty acids showed significant activity and were more active than those derived from other types of fatty acids. A variation of the amine headgroup also altered bioactivity profile remarkably, possibly by modulating cell permeability. Regarding the amine part of the molecules, N-acyl dopamines exhibited the most potent activity (IC50 similar to 2 mu M). This is the first report of the inhibitory activity of endogenous fatty acid amides and their analogues on the production of nitric oxide, cytokines (IL-1 beta, IL-6, and TNF-alpha) and the chemokine MDC. This study suggests that the enone fatty acid-derived amides (such as N-acyl ethanolamines and N-acyl amino acids) and N-acyl dopamines may be potential anti-inflammatory leads. (C) 2010 Elsevier Ltd. All rights reserved.
• CHIRAL SURFACTANTS AND METHODS FOR THEIR USE IN CHIRAL SEPARATIONS
  申请人：Waters Corporation

  公开号：EP0721446B1

  公开（公告）日：2001-07-18