Abstract
Further optimization of the potent antifungal activity of side chain analogs of the natural product FR901379 led to the discovery of compound 8 with an excellent, well-balanced profile. Potent compounds with reduced hemolytic potential were designed based upon a disruption of the linearity of the terphenyl lipophilic side chain. The optimized compound (8, FK463, micafungin) displayed the best balance and was selected as the clinical candidate.
MeSH terms
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Antifungal Agents / chemical synthesis
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Antifungal Agents / pharmacology*
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Aspergillus fumigatus / drug effects*
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Biological Products / chemical synthesis
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Biological Products / pharmacology*
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Candida albicans / drug effects*
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Echinocandins / chemical synthesis
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Echinocandins / pharmacology*
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Lipopeptides
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Lipoproteins
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Micafungin
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Microbial Sensitivity Tests
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Models, Chemical
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Peptides, Cyclic / chemical synthesis
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Peptides, Cyclic / pharmacology*
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Structure-Activity Relationship
Substances
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Antifungal Agents
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Biological Products
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Echinocandins
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FR 901379
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Lipopeptides
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Lipoproteins
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Peptides, Cyclic
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Micafungin