Abstract
The synthesis and antifungal activity of 5'- and 5'-6'-substituted azasordarin derivatives are described. Modification of the 5'-position led to the discovery of the spirocyclopentyl analogue 7g, which is the first azasordarin to register single-digit MIC values versus Aspergillus spp. Further investigation identified the 5'-i-Pr derivative 7b, which displays superior pharmacokinetic properties compared to other azasordarins.
MeSH terms
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Administration, Oral
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Animals
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Antifungal Agents / chemistry*
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Antifungal Agents / pharmacokinetics*
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Antifungal Agents / pharmacology
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Aspergillus / drug effects
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Aza Compounds / chemical synthesis*
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Aza Compounds / chemistry
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Aza Compounds / pharmacokinetics*
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Aza Compounds / pharmacology
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Glycosides / chemistry
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Indenes
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Injections, Intravenous
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Mice
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Microbial Sensitivity Tests
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Spiro Compounds / chemistry
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Spiro Compounds / pharmacokinetics
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Spiro Compounds / pharmacology
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antifungal Agents
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Aza Compounds
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Glycosides
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Indenes
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Spiro Compounds
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sordarin