Novel and highly potent histamine H3 receptor ligands. Part 2: exploring the cyclohexylamine-based series

Olivier Labeeuw; Nicolas Levoin; Olivia Poupardin-Olivier; Thierry Calmels; Xavier Ligneau; Isabelle Berrebi-Bertrand; Philippe Robert; Jeanne-Marie Lecomte; Jean-Charles Schwartz; Marc Capet

doi:10.1016/j.bmcl.2011.06.102

Novel and highly potent histamine H3 receptor ligands. Part 2: exploring the cyclohexylamine-based series

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5384-8. doi: 10.1016/j.bmcl.2011.06.102. Epub 2011 Jun 28.

Authors

Olivier Labeeuw¹, Nicolas Levoin, Olivia Poupardin-Olivier, Thierry Calmels, Xavier Ligneau, Isabelle Berrebi-Bertrand, Philippe Robert, Jeanne-Marie Lecomte, Jean-Charles Schwartz, Marc Capet

Affiliation

¹ Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France. o.labeeuw@bioprojet.com

PMID: 21783360
DOI: 10.1016/j.bmcl.2011.06.102

Abstract

Synthesis and biological evaluation of novel and potent cyclohexylamine-based histamine H3 receptor inverse agonists are described. Compounds in this newly identified series exhibited subnanomolar binding affinities for human receptor and no significant interaction with hERG channel. One derivative (10t) demonstrated enhanced in vivo efficiency and preferential brain distribution, both properties suitable for potential clinical evaluation.

MeSH terms

Animals
Cyclohexylamines / chemical synthesis
Cyclohexylamines / chemistry
Cyclohexylamines / pharmacology*
Dose-Response Relationship, Drug
Histamine Agonists / chemical synthesis
Histamine Agonists / chemistry
Histamine Agonists / pharmacology*
Humans
Ligands
Mice
Models, Molecular
Molecular Structure
Receptors, Histamine H3 / metabolism
Stereoisomerism
Structure-Activity Relationship
Trans-Activators / antagonists & inhibitors*
Trans-Activators / metabolism
Transcriptional Regulator ERG

Substances

Cyclohexylamines
ERG protein, human
Histamine Agonists
Ligands
Receptors, Histamine H3
Trans-Activators
Transcriptional Regulator ERG