Abstract
A highly potent water soluble triazole antifungal prodrug, RO0098557 (1), has been identified from its parent, the novel antifungal agent RO0094815 (2). The prodrug includes a triazolium salt linked to an aminocarboxyl moiety, which undergoes enzymatic activation followed by spontaneous chemical degradation to release 2. Prodrug 1 showed high chemical stability and water solubility and exhibited strong antifungal activity against systemic candidiasis and aspergillosis as well as pulmonary aspergillosis in rats.
MeSH terms
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Animals
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Antifungal Agents / chemical synthesis*
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Antifungal Agents / pharmacokinetics
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Antifungal Agents / pharmacology*
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Aspergillosis / drug therapy
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Aspergillosis / microbiology
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Biotransformation
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Candidiasis / drug therapy
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Candidiasis / microbiology
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Chemical Phenomena
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Chemistry, Physical
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Drug Design
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Half-Life
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Haplorhini
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Humans
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Hydrogen-Ion Concentration
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In Vitro Techniques
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Models, Molecular
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Molecular Conformation
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Prodrugs / chemical synthesis*
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Prodrugs / pharmacokinetics
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Prodrugs / pharmacology*
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Rats
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Solubility
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Solvents
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Triazoles / chemical synthesis*
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Triazoles / pharmacokinetics
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Triazoles / pharmacology*
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Water
Substances
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Antifungal Agents
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Prodrugs
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Solvents
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Triazoles
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Water