Abstract
A novel series of imidazole containing histamine H(3) receptor ligands were investigated and found to be potent functional antagonists. After improving the stability of these molecules towards liver microsomes, these compounds were found to have no appreciable affinity for CYP P450s. Subsequent in vivo experiments showed significant brain uptake of (4-chloro-phenyl)-[2-(1-isopropyl-piperidin-4-ylmethoxy)-3-methyl-3H-imidazol-4-yl]-methanone 22.
MeSH terms
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Animals
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Blood-Brain Barrier / drug effects*
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Brain / drug effects*
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Brain / metabolism
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Chemistry, Pharmaceutical / methods*
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Drug Design
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Drug Evaluation, Preclinical
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Guinea Pigs
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Histamine H3 Antagonists / chemical synthesis*
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Histamine H3 Antagonists / chemistry*
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Histamine H3 Antagonists / metabolism
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Humans
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Imidazoles / chemistry*
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Ligands
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Models, Chemical
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Protein Binding
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Rats
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Structure-Activity Relationship
Substances
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Histamine H3 Antagonists
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Imidazoles
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Ligands