Identification of a novel, orally bioavailable histamine H(3) receptor antagonist based on the 4-benzyl-(1H-imidazol-4-yl) template.
A novel series of histamine H(3) receptor antagonists, based on the 4-benzyl-(1H-imidazole-4-yl) template, incorporating urea and carbamate linkers has been prepared. Compound 3j is a selective H(3) antagonist and demonstrates excellent oral plasma levels in the rat and monkey.
Aslanian
Robert
R
The Schering Plough Research Institute, Kenilworth, NJ 07033, USA. aslanian@spcorp.com
Mutahi
Mwangi W
MW
Shih
Neng Yang
NY
McCormick
Kevin D
KD
Piwinski
John J
JJ
Ting
Pauline C
PC
Albanese
Margaret M
MM
Berlin
Michael Y
MY
Zhu
Xiaohong
X
Wong
Shing Chun
SC
Rosenblum
Stuart B
SB
Jiang
Yueheng
Y
West
Robert
R
She
Susan
S
Williams
Shirley M
SM
Bryant
Matthew
M
Hey
John A
JA
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D000882:Haplorhini; D006633:Histamine Antagonists / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D007093:Imidazoles / Q000138:chemical synthesis / Q000493:pharmacokinetics* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
D006633:Histamine Antagonists; D007093:Imidazoles; D018100:Receptors, Histamine H3