title: Novel and highly potent histamine H3 receptor ligands. Part 2: exploring the cyclohexylamine-based series.
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.
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France. o.labeeuw@bioprojet.com
authors.forename: Olivier
authors.initials: O
authors.lastname: Labeeuw
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levoin
authors.forename: Olivia
authors.initials: O
authors.lastname: Poupardin-Olivier
authors.forename: Thierry
authors.initials: T
authors.lastname: Calmels
authors.forename: Xavier
authors.initials: X
authors.lastname: Ligneau
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berrebi-Bertrand
authors.forename: Philippe
authors.initials: P
authors.lastname: Robert
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Lecomte
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Schwartz
authors.forename: Marc
authors.initials: M
authors.lastname: Capet
mesh_terms: D000818:Animals; D003514:Cyclohexylamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017442:Histamine Agonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D018100:Receptors, Histamine H3 / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: D003514:Cyclohexylamines; C072312:ERG protein, human; D017442:Histamine Agonists; D008024:Ligands; D018100:Receptors, Histamine H3; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG