title: Quinoline- and isoquinoline-sulfonamide analogs of aripiprazole: novel antipsychotic agents?
abstract: The introduction of typical antipsychotics over six decades ago signaled an important milestone in psychiatry. However, second-generation antipsychotics ameliorated the positive symptoms of schizophrenia but displayed limited effectiveness for the negative and cognitive symptoms. In addition, while the newer antipsychotics produced fewer motor side effects, the atypical antipsychotics still induced weight gain and endocrinopathies. In recent years, a third generation of antipsychotics was identified. Aripiprazole was the first approved drug acting as a D2 partial agonist/functionally selective ligand. This review presents the state of the development of novel antipsychotic dopaminergic and non-dopaminergic agents, supported by an overview of the compounds evaluated under advanced preclinical and clinical development (e.g., cariprazine and brexpiprazole). In line with the recent trends in the development of modern atypical antipsychotics, we present our strategic development of long-chain arylpiperazine-derived quinoline- and isoquinoline-sulfonamide displaying a multireceptor binding profile and partial D2 receptor agonism.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Zajdel
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marciniec
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawlowski
authors.forename: Anna
authors.initials: A
authors.lastname: Wesolowska
mesh_terms: D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000068180:Aripiprazole; D006801:Humans; D007546:Isoquinolines / Q000737:chemistry*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011485:Protein Binding; D011804:Quinolines / Q000737:chemistry*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy; D013449:Sulfonamides / Q000737:chemistry*
chemical_list: D014150:Antipsychotic Agents; D007546:Isoquinolines; D010879:Piperazines; D011804:Quinolines; D015363:Quinolones; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; D013449:Sulfonamides; D000068180:Aripiprazole; C037219:quinoline; C039109:isoquinoline