2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents.
Basic Information
ID: ALA3407422
Journal: J Med Chem
Title: 2-(2-oxo-morpholin-3-yl)-acetamide derivatives as broad-spectrum antifungal agents.
Authors: Bardiot D, Thevissen K, De Brucker K, Peeters A, Cos P, Taborda CP, McNaughton M, Maes L, Chaltin P, Cammue BP, Marchand A.
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.
CiteXplore: 25585716
DOI: 10.1021/jm501814x
Patent ID: ┄