Novel imidazole-based histamine H3 antagonists

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 v...

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Veröffentlicht in:	Bioorganic & medicinal chemistry letters 2009-02, Vol.19 (3), p.903-907
Hauptverfasser:	JABLONOWSKI, Jill A, LY, Kiev S, LOVENBERG, Timothy W, CARRUTHERS, Nicholas I, BOGENSTAETTER, Michael, DVORAK, Curt A, BOGGS, Jamin D, DVORAK, Lisa K, LORD, Brian, MILLER, Kirsten L, MAZUR, Curt, WILSON, Sandy J
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Biological and medical sciences Blood-Brain Barrier - drug effects Brain - drug effects Brain - metabolism Chemistry, Pharmaceutical - methods Drug Design Drug Evaluation, Preclinical Guinea Pigs Histamine H3 Antagonists - chemical synthesis Histamine H3 Antagonists - chemistry Histamine H3 Antagonists - metabolism Humans Imidazoles - chemistry Ligands Medical sciences Miscellaneous Models, Chemical Neuropharmacology Neurotransmitters. Neurotransmission. Receptors Pharmacology. Drug treatments Protein Binding Rats Structure-Activity Relationship
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Zusammenfassung:	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.
ISSN:	0960-894X 1464-3405
DOI:	10.1016/j.bmcl.2008.11.114