2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents.

doi:10.1021/jm501814x

Paper

2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents.

Published Jan 28, 2015 · D. Bardiot, K. Thevissen, Katrijn De Brucker

Journal of medicinal chemistry

Q1 SJR score

18

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1

Influential Citations

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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 gem-dimethyl 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.

Study Snapshot

2-(2-oxo-morpholin-3-yl)-acetamide derivatives show promising broad antifungal activity against various fungi, including Candida species, with improved plasmatic stability and in vivo efficacy in a murine model of systemic Candida albicans infection.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents.

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