Title
2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents 2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Washington, D.C. ,
Subject
Biology
Pharmacology. Therapy
Human medicine
Source (journal)
Journal of medicinal chemistry. - Washington, D.C., 1963, currens
Volume/pages
58(2015) :3 , p. 1502-1512
ISSN
0022-2623
ISI
000349573800038
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
From a fungicidal screen, we identified 2-(2-oxo-morpholin-3-yl)- acetamide derivatives as fungicidal agents against Candida species, additionally characterized by antifungal activity against Aspergillus species. However, development of this series was hampered by low plasmatic stability. Introduction of a gemdimethyl on the 6-position of the morpholin-2-one core led to considerable improvement in plasmatic stability while maintaining in vitro antifungal activity. Further optimization of the series resulted in the discovery of N-(biphenyl-3- ylmethyl)-2-(4-ethyl-6,6-dimethyl-2-oxomorpholin-3-yl)acetamide (87), which, in addition to fungicidal activity against Candida species, shows promising and broad antifungal in vitro activity against various fungi species, such as molds and dermatophytes. In vivo efficacy was also demonstrated in a murine model of systemic Candida albicans infection with a significant fungal load reduction in kidneys.
E-info
https://repository.uantwerpen.be/docman/iruaauth/3c0827/b5289dda0b7.pdf
Full text (open access)
https://repository.uantwerpen.be/docman/irua/d475ed/9879.pdf
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