629-54-9Relevant articles and documents
Different roles for the acyl chain and the amine leaving group in the substrate selectivity of N-Acylethanolamine acid amidase
Ghidini, Andrea,Scalvini, Laura,Palese, Francesca,Lodola, Alessio,Mor, Marco,Piomelli, Daniele
, p. 1411 - 1423 (2021/07/17)
N-acylethanolamine acid amidase (NAAA) is an N-terminal nucleophile (Ntn) hydrolase that catalyses the intracellular deactivation of the endogenous analgesic and anti-inflammatory agent palmitoylethanolamide (PEA). NAAA inhibitors counteract this process and exert marked therapeutic effects in animal models of pain, inflammation and neurodegeneration. While it is known that NAAA preferentially hydrolyses saturated fatty acid ethanolamides (FAEs), a detailed profile of the relationship between catalytic efficiency and fatty acid-chain 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 of the polar heads. This relationship reflects the relative stability of enzyme-substrate complexes in molecular dynamics simulations.
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.
Metal-Free Thermal Activation of Molecular Oxygen Enabled Direct α-CH2-Oxygenation of Free Amines
Ghosh, Santanu,Jana, Chandan K.
, p. 260 - 266 (2018/02/19)
Direct oxidation of α-CH2 group of free amines is hard to achieve due to the higher reactivity of amine moiety. Therefore, oxidation of amines involves the use of sophisticated metallic reagents/catalyst in the presence or absence of hazardous oxidants under sensitive reaction conditions. A novel method for direct C-H oxygenation of aliphatic amines through a metal-free activation of molecular oxygen has been developed. Both activated and unactivated free amines were oxygenated efficiently to provide a wide variety of amides (primary, secondary) and lactams under operationally simple conditions without the aid of metallic reagents and toxic oxidants. The method has been applied to the synthesis of highly functionalized amide-containing medicinal drugs, such as O-Me-alibendol and -buclosamide.
