18704-66-0Relevant articles and documents
A Convenient Protocol for the Synthesis of Fatty Acid Amides
Johansson, Silje J. R.,Johannessen, Tonje,Ellefsen, Christiane F.,Ristun, Mali S.,Antonsen, Simen,Hansen, Trond V.,Stenstrom, Yngve,Nolsoe, Jens M. J.
supporting information, p. 213 - 217 (2019/01/14)
Several classes of biologically occurring fatty acid amides have been reported from mammalian and plant sources. Many amides conjugated with fatty acids of mammalian origin exhibit specific activation of individual receptors. Their potential as pharmacological tools or as lead compounds towards the development of novel therapeutics is of great interest. Hence, access to such amides by a practical, high-yielding and scalable protocol without affecting the geometry or position of sensitive functionalities is needed. A protocol that meets all these requirements involves activation of the corresponding acid with carbonyl diimidazole (CDI) followed by reaction with the desired amine or its hydrochloride. More than fifty compounds have been prepared in generally high yields.
Modifications of the ethanolamine head in N-palmitoylethanolamine: Synthesis and evaluation of new agents interfering with the metabolism of anandamide
Vandevoorde, Séverine,Jonsson, Kent-Olov,Fowler, Christopher J.,Lambert, Didier M.
, p. 1440 - 1448 (2007/10/03)
The endogenous fatty acid amide anandamide (AEA) has, as a result of its actions on cannabinoid and vanilloid receptors, a number of important pharmacological properties including effects on nociception, memory processes, spasticity, and cell proliferation. Inhibition of the metabolism of AEA, catalyzed by fatty acid amide hydrolase (FAAH), potentiates the actions of AEA in vivo and therefore may be a useful target for drug development. In the present study, we have investigated whether substitution of the headgroup of the endogenous alternative FAAH substrate palmitoylethanolamide (PEA) can result in the identification of novel compounds preventing AEA metabolism. Thirty-seven derivatives of PEA were synthesized, with the C16 long chain of palmitic acid kept intact, and comprising 20 alkylated, 12 aromatic, and 4 halogenated amides. The ability of the PEA derivatives to inhibit FAAH-catalyzed hydrolysis of [3H]AEA was investigated using rat brain homogenates as a source of FAAH. Inhibition curves were analyzed to determine the potency of the inhibitable fraction (PI50 values) and the maximal attained inhibition for the compound, given that solubility in an aqueous environment is a major issue for these compounds. In the alkylamide family, palmitoylethylamide and palmitoylallylamide were inhibitors of AEA metabolism with PI50 values of 5.45 and 5.47, respectively. Halogenated derivatives (Cl and Br) exhibit pI50 values of ～5.5 but rather low percentages of maximal inhibition. The -OH group of the ethyl head chain of N-palmitoylethanolamine was not necessary for interaction with FAAH. Amides containing aromatic moieties were less potent inhibitors of AEA metabolism. Compounds containing amide and ester bonds, 13 and 37, showed pI50 values of 4.99 and 5.08, respectively. None of the compounds showed obvious affinity for CB1 or CB2 receptors expressed on Chinese hamster ovary (CHO) cells. It is concluded that although none of the compounds were dramatically more potent than PEA itself at reducing the metabolism of AEA, the lack of effect of the compounds at CB1 and CB2 receptors makes them useful templates for development of possible therapeutic FAAH inhibitors.
Acyl Migration from Nitrogen to Oxygen with Triphenylphosphine-tetrahalogenomethane Reagent: Synthesis of Esters from 2-Amino Alcohols
Dutta, Pradeep K.,Chaudhuri, Chandana,Mandal, Sukhendu B.,Banerjee, Ashis K.,Pakrashi, Satyesh C.,Achari, Basudeb
, p. 2180 - 2188 (2007/10/02)
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