Antidepressant and antipsychotic activity of new quinoline- and isoquinoline-sulfonamide analogs of aripiprazole targeting serotonin 5-HT1A/5-HT2A/5-HT7 and dopamine D-2/D-3 receptors

作者：Zajdel Pawel^*; Marciniec Krzysztof; Maslankiewicz Andrzej; Grychowska Katarzyna; Satala Grzegorz; Duszynska Beata; Lenda Tomasz; Siwek Agata; Nowak Gabriel; Partyka Anna; Wrobel Dagmara; Jastrzebska Wiesek Magdalena; Bojarski Andrzej J; Wesolowska Anna; Pawlowski Maciej

来源：European Journal of Medicinal Chemistry, 2013, 60: 42-50.

DOI：10.1016/j.ejmech.2012.11.042

• Quinoline-sulfonamides
• Isoquinoline-sulfonamides
• Long-chain arylpiperazines
• 2,3-Dichlorophenylpiperazine
• Serotonin
• Dopamine
• 5-HT2A antagonist
• D-2 partial agonist
• 5-HT7 antagonist
• Aripiprazole
• Depression
• Schizophrenia

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-HT1A/5-HT2A/5-HT7/D-2/D-3 profile, and behaving as 5-HT1A agonists, D-2 partial agonists, and 5-HT2A/5-HT7 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.

• 出版日期2013-2