Quinolinesulfonamides of Aryloxy-/Arylthio-ethyl Piperidines: Influence of an Arylether Fragment on 5-HT1A/5-HT7 Receptor Selectivity

• Published in: Archiv der Pharmazie (Weinheim) Vol. 346; no. 3; pp. 180 - 188
• Main Authors: Grychowska, Katarzyna, Marciniec, Krzysztof, Canale, Vittorio, Szymiec, Michał, Glanowski, Grzegorz, Satała, Grzegorz, Maślankiewicz, Andrzej, Pawłowski, Maciej, Bojarski, Andrzej J., Zajdel, Paweł
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.03.2013; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: 5-HT1A and 5-HT7 receptor affinity; Alicyclic amines; Arylpiperazine biomimetics; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Drug Design; Ethers; HEK293 Cells; Humans; Life Sciences & Biomedicine; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Piperidines - chemical synthesis; Piperidines - chemistry; Piperidines - pharmacology; Protein Binding; Quinoline sulfonamides; Quinolines - chemical synthesis; Quinolines - chemistry; Quinolines - pharmacology; Radioligand Assay; Receptor, Serotonin, 5-HT1A - genetics; Receptor, Serotonin, 5-HT1A - metabolism; Receptors, Serotonin - genetics; Receptors, Serotonin - metabolism; Science & Technology; Solid-phase synthesis; Solid-Phase Synthesis Techniques; Solids; Structure-Activity Relationship; Sulfonamides - chemical synthesis; Sulfonamides - chemistry; Sulfonamides - pharmacology; Transfection; LIGANDS; AFFINITY; Quinoline sulfonamides; SULFONAMIDES; 5-HT1A and 5-HT7 receptor affinity; Arylpiperazine biomimetics; Solid-phase synthesis; ANTAGONISTS; DERIVATIVES; Alicyclic amines
• ISSN: 0365-6233; 1521-4184
• DOI: 10.1002/ardp.201200322

The solid‐phase synthesis of a new series of 19 biomimetics of long‐chain arylpiperazines, namely flexible quinoline sulfonamides of aryl(heteroaryl)oxy‐/heteroarylthio‐ethyl 4‐aminomethylpiperidines, is reported. Various structural modifications applied followed by biological evaluation for 5‐HT1A, 5‐HT6, and 5‐HT7 receptors gave further support of a possible replacement of arylpiperazine with aryloxy‐/arylthio‐ethyl derivatives of alicyclic amines and control of receptor selectivity upon diversification in the aryl(heteroaryl)oxy‐/heteroarylthio‐ethyl fragment. The solid‐phase synthesis of a new series of 19 biomimetics of long‐chain arylpiperazines is reported. Biological evaluation for 5‐HT1A, 5‐HT6, and 5‐HT7 receptors supported the possible replacement of the arylpiperazine with aryloxy‐/arylthio‐ethyl derivatives of alicyclic amines and the control of receptor selectivity upon diversification in the aryl(heteroaryl)oxy‐/heteroarylthio‐ethyl fragment.