1.
Bioorg Med Chem Lett
; 16(4): 989-94, 2006 Feb 15.
Article
in English
| MEDLINE
| ID: mdl-16297617
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.
Subject(s)
Cytochrome P-450 Enzyme Inhibitors , Enzyme Inhibitors/pharmacology , Histamine Antagonists/pharmacology , Imidazoles/pharmacology , Piperidines/pharmacology , Receptors, Histamine H3/drug effects , Animals , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Guinea Pigs , Haplorhini , Histamine Antagonists/chemical synthesis , Histamine Antagonists/chemistry , Humans , Imidazoles/chemical synthesis , Imidazoles/chemistry , Molecular Structure , Piperidines/chemical synthesis , Piperidines/chemistry , Rats , Structure-Activity Relationship , Tissue Distribution
2.
Bioorg Med Chem Lett
; 16(2): 395-9, 2006 Jan 15.
Article
in English
| MEDLINE
| ID: mdl-16246552
ABSTRACT
We report the discovery of novel histamine H(3) receptor antagonists based on 4-[(1H-imidazol-4-yl)methyl]piperidine. The most potent compounds in the series (e.g., 7) result from the attachment of a substituted aniline amide to the main pharmacophore piperidine via a two-methylene linker.
