87568-46-5Relevant academic research and scientific papers
CARBAMATE DERIVATIVES OF LACTAM BASED N-ACYLETHANOLAMINE ACID AMIDASE (NAAA) INHIBITORS
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, (2014/09/29)
Described herein are compounds and pharmaceutical compositions which inhibit N-acylethanolamine acid amidase (NAAA). Described herein are methods for synthesizing the compounds set forth herein and methods for formulating these compounds as pharmaceutical compositions which include these compounds. Also described herein are methods of inhibiting NAAA in order to sustain the levels of palmitoylethanolamide (PEA) and other N-acylethanolamines (NAE) that are substrates for NAAA, in conditions characterized by reduced concentrations of NAE. Also, described here are methods of treating and ameliorating pain, inflammation, inflammatory diseases, and other disorders in which modulation of fatty acid ethanolamides is clinically or therapeutically relevant or in which decreased levels of NAE are associated with the disorder.
3-Aminoazetidin-2-one derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors suitable for systemic administration
Fiasella, Annalisa,Nuzzi, Andrea,Summa, Maria,Armirotti, Andrea,Tarozzo, Glauco,Tarzia, Giorgio,Mor, Marco,Bertozzi, Fabio,Bandiera, Tiziano,Piomelli, Daniele
, p. 1602 - 1614 (2014/07/21)
N-Acylethanolamine acid amidase (NAAA) is a cysteine hydrolase that catalyzes the hydrolysis of endogenous lipid mediators such as palmitoylethanolamide (PEA). PEA has been shown to exert anti-inflammatory and antinociceptive effects in animals by engaging peroxisome proliferator-activated receptor α (PPAR-α). Thus, preventing PEA degradation by inhibiting NAAA may provide a novel approach for the treatment of pain and inflammatory states. Recently, 3-aminooxetan-2-one compounds were identified as a class of highly potent NAAA inhibitors. The utility of these compounds is limited, however, by their low chemical and plasma stabilities. In the present study, we synthesized and tested a series of N-(2-oxoazetidin-3-yl)amides as a novel class of NAAA inhibitors with good potency and improved physicochemical properties, suitable for systemic administration. Moreover, we elucidated the main structural features of 3-aminoazetidin-2-one derivatives that are critical for NAAA inhibition. Stability is the key: α-Amino-β-lactams were synthesized as amide derivatives, and the effect of the azetidin-2-one ring, the stereochemistry at the α-position, and the functionalization of the α-amino group were studied with regard to N-acylethanolamine acid amidase inhibitory potency and hydrolytic and plasma stability.
Synthesis of β-lactam antibiotics by the sulfeno-cycloamination
Ihara,Haga,Yonekura,et al.
, p. 7345 - 7352 (2007/10/02)
A novel efficient beta -lactam synthesis was achieved by two successive processes (sulfeno-cycloamination), addition of phenysulfenyl chloride to alpha , beta -unsaturated amides followed by base treatment. Key synthetic intermediates of monobactams and nocardicin derivatives were obtained via this method. construction of the 1-carbapenam ring system by the sulfenocycloamination is also described.
