Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring.
Three novel series of histamine H(4) receptor (H(4)R) antagonists containing the 2-aminopyrimidine motif are reported. The best of these compounds display good in vitro potency in both functional and binding assays. In addition, representative compounds are able to completely block itch responses when dosed ip in a mouse model of H(4)-agonist induced scratching, thus demonstrating their activities as H(4)R antagonists.
Koenig
John R
JR
Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6100, USA. john.r.koenig@abbott.com
Liu
Huaqing
H
Drizin
Irene
I
Witte
David G
DG
Carr
Tracy L
TL
Manelli
Arlene M
AM
Milicic
Ivan
I
Strakhova
Marina I
MI
Miller
Thomas R
TR
Esbenshade
Timothy A
TA
Brioni
Jorge D
JD
Cowart
Marlon
M
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors*; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4
D000631:Aminopyridines; D006633:Histamine Antagonists; C498829:Hrh4 protein, mouse; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D000074040:Receptors, Histamine H4; C032439:alpha-aminopyridine