Abstract
The preparation and structure-activity-relationships of novel pyrrolidine-carboxamides and oxadiazoles are described. Compounds in this series were found to be potent hNK(1) antagonists in vitro and efficacious in vivo with minimal interactions with P(450) liver enzymes. Oxadiazole analog 22 was determined to have excellent hNK(1) binding affinity, functional activity, and a good PD response in vivo.
MeSH terms
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Alkaloids / chemistry
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Alkaloids / pharmacology*
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Antiviral Agents / chemistry
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Antiviral Agents / pharmacology*
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Cell Line
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Chromatography, Ion Exchange
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Hepatitis B Surface Antigens / metabolism
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Hepatitis B e Antigens / metabolism
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Hepatitis B virus / drug effects*
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Humans
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Magnetic Resonance Spectroscopy
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Menispermaceae / chemistry*
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Models, Molecular
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Molecular Conformation
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Oxadiazoles / chemistry
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Oxadiazoles / pharmacology*
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Pyrrolidines / chemistry
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Pyrrolidines / pharmacology*
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Spectrometry, Mass, Electrospray Ionization
Substances
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Alkaloids
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Antiviral Agents
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Hepatitis B Surface Antigens
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Hepatitis B e Antigens
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Oxadiazoles
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Pyrrolidines