title: Improving selectivity of dopamine D3 receptor ligands.
abstract: The seminal human dopamine D3 receptor (hD3R) ligand BP 897 has shown interesting properties during clinical trials. However, its lack of selectivity towards human adrenergic receptor impedes further development. Two approaches were followed to increase hD3R selectivity. The lead optimisation succeeded, we disclose here ligands with subnanomolar potency for D3R, combined with a good selectivity for the closely related human dopamine D2 and human adrenergic alpha-1 receptors.
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France. Electronic address: m.capet@bioprojet.com.
authors.forename: Marc
authors.initials: M
authors.lastname: Capet
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Calmels
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Levoin
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.
authors.forename: Denis
authors.initials: D
authors.lastname: Danvy
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Berrebi-Bertrand
authors.affiliation: Heinrich Heine University Düsseldorf, Universitaetsstr. 1, 40225 Duesseldorf, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Schwartz
authors.affiliation: Bioprojet-Biotech, 4 rue du Chesnay Beauregard, BP 96205, 35762 Saint-Grégoire, France.
authors.forename: Jeanne-Marie
authors.initials: JM
authors.lastname: Lecomte
mesh_terms: D001665:Binding Sites; D006801:Humans; D007700:Kinetics; D008024:Ligands; D062105:Molecular Docking Simulation; D010879:Piperazines / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; D050637:Receptors, Dopamine D3; C120565:BP 897
keywords: Adrenergic receptor; Dopamine receptor; Selectivity