Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring

John R Koenig; Huaqing Liu; Irene Drizin; David G Witte; Tracy L Carr; Arlene M Manelli; Ivan Milicic; Marina I Strakhova; Thomas R Miller; Timothy A Esbenshade; Jorge D Brioni; Marlon Cowart

doi:10.1016/j.bmcl.2010.01.131

Rigidified 2-aminopyrimidines as histamine H4 receptor antagonists: effects of substitution about the rigidifying ring

Bioorg Med Chem Lett. 2010 Mar 15;20(6):1900-4. doi: 10.1016/j.bmcl.2010.01.131. Epub 2010 Feb 1.

Authors

John R Koenig¹, Huaqing Liu, Irene Drizin, David G Witte, Tracy L Carr, Arlene M Manelli, Ivan Milicic, Marina I Strakhova, Thomas R Miller, Timothy A Esbenshade, Jorge D Brioni, Marlon Cowart

Affiliation

¹ Neuroscience Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064-6100, USA. john.r.koenig@abbott.com

PMID: 20171098
DOI: 10.1016/j.bmcl.2010.01.131

Abstract

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.

MeSH terms

Aminopyridines / pharmacology*
Animals
Histamine Antagonists / pharmacology*
Humans
Mice
Receptors, G-Protein-Coupled / antagonists & inhibitors*
Receptors, Histamine
Receptors, Histamine H4

Substances

Aminopyridines
Histamine Antagonists
Hrh4 protein, mouse
Receptors, G-Protein-Coupled
Receptors, Histamine
Receptors, Histamine H4
alpha-aminopyridine