Abstract
A novel series of histamine H3 receptor antagonists based on the 4-[(1H-imidazol-4-yl)methyl]piperidine template displaying low CYP2D6 and CYP3A4 inhibitory profiles has been identified. Structural features responsible for the reduction of P450 activity, a typical liability of 4-substituted imidazoles, have been established.
MeSH terms
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Animals
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Cytochrome P-450 Enzyme Inhibitors*
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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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Guinea Pigs
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Haplorhini
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Histamine Antagonists / chemical synthesis
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Histamine Antagonists / chemistry
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Histamine Antagonists / pharmacology*
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Humans
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Imidazoles / chemical synthesis
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Imidazoles / chemistry
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Imidazoles / pharmacology*
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Molecular Structure
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Piperidines / chemical synthesis
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Piperidines / chemistry
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Piperidines / pharmacology*
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Rats
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Receptors, Histamine H3 / drug effects*
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Structure-Activity Relationship
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Tissue Distribution
Substances
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Cytochrome P-450 Enzyme Inhibitors
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Enzyme Inhibitors
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Histamine Antagonists
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Imidazoles
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Piperidines
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Receptors, Histamine H3