title: Novel and highly potent histamine H3 receptor ligands. Part 1: withdrawing of hERG activity.
abstract: Pre-clinical investigation of some aryl-piperidinyl ether histamine H3 receptor antagonists revealed a strong hERG binding. To overcome this issue, we have developed a QSAR model specially dedicated to H3 receptor ligands. This model was designed to be directly applicable in medicinal chemistry with no need of molecular modeling. The resulting recursive partitioning trees are robust (80-85% accuracy), but also simple and comprehensible. A novel promising lead emerged from our work and the structure-activity relationships are presented.
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint Grégoire, France. n.levoin@bioprojet.com
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levoin
authors.forename: Olivier
authors.initials: O
authors.lastname: Labeeuw
authors.forename: Thierry
authors.initials: T
authors.lastname: Calmels
authors.forename: Olivia
authors.initials: O
authors.lastname: Poupardin-Olivier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berrebi-Bertrand
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: D001665:Binding Sites / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004987:Ethers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D054828:Histamine H3 Antagonists / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013237:Stereoisomerism; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D004987:Ethers; D054828:Histamine H3 Antagonists; D008024:Ligands; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG