Reduction of CYP450 inhibition in the 4-[(1H-imidazol-4-yl)methyl]piperidine series of histamine H3 receptor antagonists.
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.
Berlin
Michael
M
The Schering Plough Research Institute, 2015 Galloping Hill Rd. Kenilworth, NJ 07033, USA. michael.berlin@spcorp.com
Ting
Pauline C
PC
Vaccaro
Wayne D
WD
Aslanian
Robert
R
McCormick
Kevin D
KD
Lee
Joe F
JF
Albanese
Margaret M
MM
Mutahi
Mwangi W
MW
Piwinski
John J
JJ
Shih
Neng-Yang
NY
Duguma
Luli
L
Solomon
Daniel M
DM
Zhou
Wei
W
Sher
Rosy
R
Favreau
Leonard
L
Bryant
Matthew
M
Korfmacher
Walter A
WA
Nardo
Cymbelene
C
West
Robert E
RE
Anthes
John C
JC
Williams
Shirley M
SM
Wu
Ren-Long
RL
Susan She
H
H
Rivelli
Maria A
MA
Corboz
Michel R
MR
Hey
John A
JA
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
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D006633:Histamine Antagonists; D007093:Imidazoles; D010880:Piperidines; D018100:Receptors, Histamine H3