N1-Azinylsulfonyl-1H-indoles: 5-HT6 Receptor Antagonists with Procognitive and Antidepressant-Like Properties

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• 作者：Paweł Zajdel ; Krzysztof Marciniec ; Grzegorz Satała ; Vittorio Canale ; Tomasz Kos ; Anna Partyka ; Magdalena Jastrzębska-Więsek ; Anna Wesołowska ; Agnieszka Basińska-Ziobroń ; Jacek Wójcikowski ; Władysława A. Daniel ; Andrzej J. Bojarski ; Piotr Popik
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：June 9, 2016
• 年：2016
• 卷：7
• 期：6
• 页码：618-622
• 全文大小：326K
• 年卷期：0
• ISSN：1948-5875

文摘

A series of N1-azinylsulfonyl-3-(1,2,3,6,tetrahyrdopyridin-4-yl)-1H-indole derivatives was designed to obtain highly potent 5-HT₆ receptor ligands. The study allowed for the identification of 25 (4-{[5-methoxy-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indol-1-yl]sulfonyl}isoquinoline), a potent and selective 5-HT₆ receptor antagonist. The selected compound, was evaluated in vivo in a novel object recognition (NOR) and forced swim (FST) tests in rats, demonstrating distinct pro-cognitive and antidepressant-like properties (MED = 1 mg/kg and 0.1 mg/kg, i.p., respectively). Compound SB-742457, used as comparator, reversed memory deficits in NOR task in similar doses, while in FST it was active in 10–30-fold higher dose (3 mg/kg). In contrast to SB-742457, which was active in Vogel test (MED = 3 mg/kg), compound 25 displayed no anxiolytic activity.