Abstract
A novel series of pyridazinone analogs has been developed as potent β-1,3-glucan synthase inhibitors through structure-activity relationship study of the lead 5-[4-(benzylsulfonyl)piperazin-1-yl]-4-morpholino-2-phenyl-pyridazin-3(2H)-one (1). The effect of changes to the core structure is described in detail. Optimization of the sulfonamide moiety led to the identification of important compounds with much improved systematic exposure while retaining good antifungal activity against the fungal strains Candida glabrata and Candida albicans.
Published by Elsevier Ltd.
MeSH terms
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Antifungal Agents / chemical synthesis
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Antifungal Agents / chemistry
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Antifungal Agents / pharmacology
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Candida albicans / drug effects
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Candida glabrata / drug effects
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Glucosyltransferases / antagonists & inhibitors*
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Molecular Structure
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Pyridazines / chemical synthesis*
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Pyridazines / chemistry
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Pyridazines / pharmacology*
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Structure-Activity Relationship
Substances
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Antifungal Agents
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Enzyme Inhibitors
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Pyridazines
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Glucosyltransferases
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glucan synthase