1414264-06-4Relevant academic research and scientific papers
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.
, 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.
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, Pawe?,Kurczab, Rafa?,Grychowska, Katarzyna,Sata?a, Grzegorz,Paw?owski, MacIej,Bojarski, Andrzej J.
, p. 348 - 360 (2013/01/15)
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.
