title: Reduction of CYP450 inhibition in the 4-[(1H-imidazol-4-yl)methyl]piperidine series of histamine H3 receptor antagonists.
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.
authors.affiliation: The Schering Plough Research Institute, 2015 Galloping Hill Rd. Kenilworth, NJ 07033, USA. michael.berlin@spcorp.com
authors.forename: Michael
authors.initials: M
authors.lastname: Berlin
authors.forename: Pauline C
authors.initials: PC
authors.lastname: Ting
authors.forename: Wayne D
authors.initials: WD
authors.lastname: Vaccaro
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Kevin D
authors.initials: KD
authors.lastname: McCormick
authors.forename: Joe F
authors.initials: JF
authors.lastname: Lee
authors.forename: Margaret M
authors.initials: MM
authors.lastname: Albanese
authors.forename: Mwangi W
authors.initials: MW
authors.lastname: Mutahi
authors.forename: John J
authors.initials: JJ
authors.lastname: Piwinski
authors.forename: Neng-Yang
authors.initials: NY
authors.lastname: Shih
authors.forename: Luli
authors.initials: L
authors.lastname: Duguma
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Solomon
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Rosy
authors.initials: R
authors.lastname: Sher
authors.forename: Leonard
authors.initials: L
authors.lastname: Favreau
authors.forename: Matthew
authors.initials: M
authors.lastname: Bryant
authors.forename: Walter A
authors.initials: WA
authors.lastname: Korfmacher
authors.forename: Cymbelene
authors.initials: C
authors.lastname: Nardo
authors.forename: Robert E
authors.initials: RE
authors.lastname: West
authors.forename: John C
authors.initials: JC
authors.lastname: Anthes
authors.forename: Shirley M
authors.initials: SM
authors.lastname: Williams
authors.forename: Ren-Long
authors.initials: RL
authors.lastname: Wu
authors.forename: H
authors.initials: H
authors.lastname: Susan She
authors.forename: Maria A
authors.initials: MA
authors.lastname: Rivelli
authors.forename: Michel R
authors.initials: MR
authors.lastname: Corboz
authors.forename: John A
authors.initials: JA
authors.lastname: Hey
mesh_terms: D000818:Animals; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006168:Guinea Pigs; D000882:Haplorhini; D006633:Histamine Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; D018100:Receptors, Histamine H3