1019374-12-9Relevant articles and documents
N-Alkylated arylsulfonamides of (aryloxy)ethyl piperidines: 5-HT7 receptor selectivity versus multireceptor profile
Canale, Vittorio,Kurczab, Rafa?,Partyka, Anna,Sata?a, Grzegorz,S?oczyńska, Karolina,Kos, Tomasz,Jastrz?bska-Wi?sek, Magdalena,Siwek, Agata,P?kala, Elzbieta,Bojarski, Andrzej J.,Weso?owska, Anna,Popik, Piotr,Zajdel, Pawe?
, p. 130 - 139 (2016)
The N-alkylation of the sulfonamide moiety, in a group of arylsulfonamide derivatives of (aryloxy)ethyl piperidines, may be considered as a strategy for the design of selective 5-HT7 receptor ligands or multifunctional agents to extend a polyph
Amino Acid Hot Spots of Halogen Bonding: A Combined Theoretical and Experimental Case Study of the 5-HT7 Receptor
Kurczab, Rafa,Canale, Vittorio,Sataa, Grzegorz,Zajdel, Pawea,Bojarski, Andrzej J.
supporting information, p. 8717 - 8733 (2018/10/02)
A computational approach combining a structure-activity relationship library of halogenated and the corresponding unsubstituted ligands (called XSAR) with QM-based molecular docking and binding free energy calculations was used to search for amino acids frequently targeted by halogen bonding (hot spots) in a 5-HT7R as a case study. The procedure identified two sets of hot spots, extracellular (D2.65, T2.64, and E7.35) and transmembrane (C3.36, T5.39, and S5.42), which were further verified by a synthesized library of halogenated arylsulfonamide derivatives of (aryloxy)ethylpiperidines. It was found that a halogen bond formed between T5.39 and a bromine atom at 3-position of the aryloxy fragment caused the most remarkable, 35-fold increase in binding affinity for 5-HT7R when compared to the nonhalogenated analog. The proposed paradigm of halogen bonding hot spots was additionally verified on D4 dopamine receptor showing that it can be used in rational drug design/optimization for any protein target.
The multiobjective based design, synthesis and evaluation of the arylsulfonamide/amide derivatives of aryloxyethyl and arylthioethyl-piperidines and pyrrolidines as a novel class of potent 5-HT7 receptor antagonists
Zajdel, Pawel,Grychowska, Katarzyna,Pawlowski, MacIej,Kurczab, Rafal,Satala, Grzegorz,Bojarski, Andrzej J.
supporting information, p. 348 - 360,13 (2012/12/11)
An analysis of the virtual combinatorial library was used for refining a pilot set of 34 derivatives and designing a targeted 38-member library of the arylamide and arylsulfonamide derivatives of aryloxyethyl- and arylthioethyl- piperidines and pyrrolidines. All compounds 24-95 were synthesized according to an elaborated parallel solid-phase method and were biologically evaluated for their affinity for 5-HT7R. Additionally, the targeted library members were tested for 5-HT1A, 5-HT6, and D2 receptors. Selected compounds of particular interest were examined for their intrinsic activity at 5-HT7R in vitro employing a cAMP assay. The study allowed us to identify compound 68 (4-fluoro-N-(1-{2-[(propan-2-yl) phenoxy]ethyl}piperidin-4-yl) benzenesulfonamide) as a potent 5-HT7R ligand (Ki = 0.3 nM) with strong antagonistic properties (K b = 1 nM) and a 1450-fold selectivity over 5-HT1ARs.
