title: Synthesis, binding affinity and SAR of new benzolactam derivatives as dopamine D3 receptor ligands.
abstract: A series of new benzolactam derivatives was synthesized and the derivatives were evaluated for their affinities at the dopamine D(1), D(2), and D(3) receptors. Some of these compounds showed high D(2) and/or D(3) affinity and selectivity over the D(1) receptor. The SAR study of these compounds revealed structural characteristics that decisively influenced their D(2) and D(3) affinities. Structural models of the complexes between some of the most representative compounds of this series and the D(2) and D(3) receptors were obtained with the aim of rationalizing the observed experimental results. Moreover, selected compounds showed moderate binding affinity on 5-HT(2A) which could contribute to reducing the occurrence of extrapyramidal side effects as potential antipsychotics.
authors.affiliation: Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
authors.forename: Raquel
authors.initials: R
authors.lastname: Ortega
authors.forename: Enrique
authors.initials: E
authors.lastname: Raviña
authors.forename: Christian F
authors.initials: CF
authors.lastname: Masaguer
authors.forename: Filipe
authors.initials: F
authors.lastname: Areias
authors.forename: José
authors.initials: J
authors.lastname: Brea
authors.forename: María I
authors.initials: MI
authors.lastname: Loza
authors.forename: Laura
authors.initials: L
authors.lastname: López
authors.forename: Jana
authors.initials: J
authors.lastname: Selent
authors.forename: Manuel
authors.initials: M
authors.lastname: Pastor
authors.forename: Ferran
authors.initials: F
authors.lastname: Sanz
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001570:Benzodiazepinones / Q000138:chemical synthesis* / Q000494:pharmacology; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D007769:Lactams / Q000737:chemistry*; D008024:Ligands; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D010879:Piperazines / Q000737:chemistry; D017448:Receptors, Dopamine D2 / Q000737:chemistry*; D050637:Receptors, Dopamine D3 / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D014150:Antipsychotic Agents; D001570:Benzodiazepinones; D007769:Lactams; D008024:Ligands; D010879:Piperazines; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3