The synthesis and structure-activity relationship of 4-benzimidazolyl-piperidinylcarbonyl-piperidine analogs as histamine H3 antagonists.
A structure-activity relationship study of the lead piperazinylcarbonylpiperidine compound 3 resulted in the identification of 4-benzimidazolyl-piperidinylcarbonyl-piperidine 6h as a histamine-3 (H(3)) receptor antagonist. Additional optimization of 6h led to the identification of compounds 11i-k with K(i) <or= 0.5 nM and good in vivo activity.
Ting
Pauline C
PC
Department of Chemical Research, Merck Research Laboratories, Kenilworth, NJ 07033, USA. pauline.ting@merck.com
Lee
Joe F
JF
Albanese
Margaret M
MM
Wu
Jie
J
Aslanian
Robert
R
Favreau
Leonard
L
Nardo
Cymbelene
C
Korfmacher
Walter A
WA
West
Robert E
RE
Williams
Shirley M
SM
Anthes
John C
JC
Rivelli
Maria A
MA
Corboz
Michel R
MR
Hey
John A
JA
D054828:Histamine H3 Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D054828:Histamine H3 Antagonists; D010880:Piperidines