| Autor: |
Fiasella, A, Nuzzi, A, Summa, M, Armirotti, A, Tarozzo, G, Tarzia, G, Mor, M, Bertozzi, F, Bandiera, T, Piomelli, D |
| Jazyk: |
angličtina |
| Rok vydání: |
2014 |
| Zdroj: |
Fiasella, A; Nuzzi, A; Summa, M; Armirotti, A; Tarozzo, G; Tarzia, G; et al.(2014). 3-Aminoazetidin-2-one derivatives as N-acylethanolamine acid amidase (NAAA) inhibitors suitable for systemic administration. ChemMedChem, 9(7), 1602-1614. doi: 10.1002/cmdc.201300546. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/9p17d204 |
| DOI: |
10.1002/cmdc.201300546. |
| Popis: |
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. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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