title: Antidepressant and antipsychotic activity of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole targeting serotonin 5-HT₁A/5-HT₂A/5-HT₇ and dopamine D₂/D₃ receptors.
abstract: A series of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole was synthesized to explore the influence of two structural features - replacement of ether/amide moiety with sulfonamide one, and localization of a sulfonamide group in the azine moiety. In contrast to aripiprazole, compound 33 (N-(3-(4-(2,3-dichlorophenyl)piperazin-1-yl)propyl)quinoline-7-sulfonamide) and 39 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)isoquinoline-3-sulfonamide) displaying multireceptor 5-HT(1A)/5-HT(2A)/5-HT(7)/D(2)/D(3) profile, and behaving as 5-HT(1A) agonists, D(2) partial agonists, and 5-HT(2A)/5-HT(7) antagonists, produced significant antidepressant activity in FST in mice. On the other hand, their 4-isoquinolinyl analog 40 (N-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butyl)isoquinoline-4-sulfonamide), with similar receptor binding and functional profile, additionally displayed remarkable antipsychotic properties in the MK-801-induced hyperlocomotor activity in mice.
authors.affiliation: Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. pawel.zajdel@uj.edu.pl
authors.forename: Paweł
authors.initials: P
authors.lastname: Zajdel
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Marciniec
authors.forename: Andrzej
authors.initials: A
authors.lastname: Maślankiewicz
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Grychowska
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Satała
authors.forename: Beata
authors.initials: B
authors.lastname: Duszyńska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Lenda
authors.forename: Agata
authors.initials: A
authors.lastname: Siwek
authors.forename: Gabriel
authors.initials: G
authors.lastname: Nowak
authors.forename: Anna
authors.initials: A
authors.lastname: Partyka
authors.forename: Dagmara
authors.initials: D
authors.lastname: Wróbel
authors.forename: Magdalena
authors.initials: M
authors.lastname: Jastrzębska-Więsek
authors.forename: Andrzej J
authors.initials: AJ
authors.lastname: Bojarski
authors.forename: Anna
authors.initials: A
authors.lastname: Wesołowska
authors.forename: Maciej
authors.initials: M
authors.lastname: Pawłowski
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014150:Antipsychotic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000068180:Aripiprazole; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009043:Motor Activity / Q000187:drug effects; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D065127:Dopamine D2 Receptor Antagonists; D007546:Isoquinolines; D010879:Piperazines; D011804:Quinolines; D015363:Quinolones; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; D013449:Sulfonamides; D016291:Dizocilpine Maleate; D000068180:Aripiprazole