2. Academic Validation
  3. 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

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

  • Eur J Med Chem. 2013 Feb:60:42-50. doi: 10.1016/j.ejmech.2012.11.042.
Paweł Zajdel 1,  Krzysztof Marciniec,  Andrzej Maślankiewicz,  Katarzyna Grychowska,  Grzegorz Satała,  Beata Duszyńska,  Tomasz Lenda,  Agata Siwek,  Gabriel Nowak,  Anna Partyka,  Dagmara Wróbel,  Magdalena Jastrzębska-Więsek,  Andrzej J Bojarski,  Anna Wesołowska,  Maciej Pawłowski
Affiliations

Affiliation

  • 1 Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. [email protected]
PMID: 23279866 DOI: 10.1016/j.ejmech.2012.11.042
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.

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