Design and synthesis of potential inhibitors of the ergosterol biosynthesis as antifungal agents
A series of azolylmethyloxolane derivatives with modified sterol side-chain structures, designed as potential dual functional inhibitors of cytochrome P450 14α-demethylase (14DM) and Δ 24-sterol methyltransferase (24-SMT) based on the common characteristic features of 24-aminosterols and azole antif...
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Veröffentlicht in: | Bioorganic & medicinal chemistry 2000-10, Vol.8 (10), p.2475-2486 |
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Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
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Online-Zugang: | Volltext |
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Zusammenfassung: | A series of azolylmethyloxolane derivatives with modified sterol side-chain structures, designed as potential dual functional inhibitors of cytochrome P450 14α-demethylase (14DM) and Δ
24-sterol methyltransferase (24-SMT) based on the common characteristic features of 24-aminosterols and azole antifungal agents, were synthesized and evaluated for their antifungal activities and inhibitory activities of 14DM and 24-SMT. Among these compounds, imidazolylmethyloxolane derivatives
28a and
28b showed potent in vitro antifungal activities comparable to those of itraconazole. However, the in vitro bioactivities have not been linearly translated into in vivo protection data for some unknown reasons. |
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ISSN: | 0968-0896 1464-3391 |
DOI: | 10.1016/S0968-0896(00)00177-2 |