Identification and hit-to-lead exploration of a novel series of histamine H4 receptor inverse agonists

The hit-to-lead exploration of a series of novel, potent and selective series of histamine H4 receptor inverse agonists originating from a virtual screening approach is described. The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H 4 receptor inverse...

Full description

Saved in:
Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 2010-04, Vol.20 (8), p.2516-2519
Main Authors: Cramp, Sue, Dyke, Hazel J., Higgs, Christopher, Clark, David E., Gill, Matthew, Savy, Pascal, Jennings, Neil, Price, Steve, Lockey, Peter M., Norman, Dennis, Porres, Soraya, Wilson, Francis, Jones, Alison, Ramsden, Nigel, Mangano, Raffaella, Leggate, Dan, Andersson, Marie, Hale, Richard
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Biological Availability
Drug Discovery
Hiatamine H4
Histamine and antagonists. Allergy
Histamine Antagonists - chemistry
Histamine Antagonists - pharmacokinetics
Histamine Antagonists - pharmacology
Hit-to-lead
Inhibitory Concentration 50
Macaca fascicularis
Medical sciences
Pharmacology. Drug treatments
Rats
Receptors, G-Protein-Coupled - antagonists & inhibitors
Receptors, Histamine
Receptors, Histamine H4
Stereoisomerism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The hit-to-lead exploration of a series of novel, potent and selective series of histamine H4 receptor inverse agonists originating from a virtual screening approach is described. The identification and hit-to-lead exploration of a novel, potent and selective series of histamine H 4 receptor inverse agonists is described. The initial hit, 3A (IC 50 19 nM) was identified by means of a ligand-based virtual screening approach. Subsequent medicinal chemistry exploration yielded 18I which possessed increased potency ( R-enantiomer IC 50 1 nM) as well as enhanced microsomal stability.
ISSN:0960-894X
1464-3405
DOI:10.1016/j.bmcl.2010.02.097