Arylsulfonamide derivatives of (aryloxy)ethylpiperidines as selective 5-HT7 receptor antagonists and their psychotropic propertiesElectronic supplementary information (ESI) available. See DOI: 10.1039/c5md00166h

• Main Authors: Zajdel, Pawe, Canale, Vittorio, Partyka, Anna, Marciniec, Krzysztof, Kurczab, Rafa, Sata a, Grzegorz, Siwek, Agata, Jastrz bska-Wi sek, Magdalena, Weso owska, Anna, Kos, Tomasz, Popik, Piotr, Bojarski, Andrzej J
• Format: Journal Article
• Language: English
• Published: 08.07.2015
• ISSN: 2040-2503; 2040-2511
• DOI: 10.1039/c5md00166h

A series of alkyl/arylsulfonamide derivatives of (aryloxy)ethylpiperidines as highly potent 5-HT 7 receptor antagonists has been developed through structure-based design on the previously identified compound PZ-766. This resulted in highly potent antagonist 10 (3-fluoro- N -(1-{2-[(propan-2-yl)phenoxy]ethyl}piperidin-4-yl)-benzenesulfonamide) which was more active in vivo than PZ-766 and SB-269970 in forced swim test in mice (MED = 2.5 mg kg −1 ), and displayed comparable effects to SB-269970 in four-plate test in mice (MED = 1.25 mg kg −1 ) and novel object recognition test in rats (MED = 1 mg kg −1 ). The results highlight the antidepressant, anxiolytic and pro-cognitive potential of the arylsulfonamide derivatives of (aryloxy)ethylpiperidines with 5-HT 7 receptor antagonist properties and warrant further studies to explore their therapeutic potential for the treatment of CNS disorders. A novel series of potent 5-HT 7 receptor antagonist and their antidepressant, anxiolytic and pro-cognitive properties is described.