1262059-05-1Relevant articles and documents
Towards new 5-HT7 antagonists among arylsulfonamide derivatives of (aryloxy)ethyl-alkyl amines: Multiobjective based design, synthesis, and antidepressant and anxiolytic properties
Canale, Vittorio,Kurczab, Rafa,Partyka, Anna,Sataa, Grzegorz,Ledna, Tomasz,Jastrzebska-Wiesek, Magdalena,Wesoowska, Anna,Bojarski, Andrzej J.,Zajdel, Pawel
supporting information, p. 334 - 346 (2015/12/23)
A series of 39 arylsulfonamide/amide derivatives of (aryloxy)ethyl alkyl amines, was designed with the support of the Virtual Combinatorial Library-Virtual Screening protocol, and synthesized using solidphase methodologies. Representative compounds were biologically evaluated for their affinity for 5-HT7Rs and for their selectivity over related 5-HTRs (5-HT1ARs, 5-HT2ARs, 5-HT6Rs), dopamine D2Rs and adrenergic a1Rs. The study identified the derivatives 27 (3-fluoro-N-{1-[2-(2-cyclopentylphenoxy) ethyl]piperidin-4-yl}-benzenesulfonamide; PZ-1417) and 35 (4-fluoro-N-(1-{2-[(propan-2-yl)phenoxy] ethyl}-8-azabicyclo[3.2.1]octan-3-yl)-benzenesulfonamide; PZ-1150) as being potent 5-HT7R antagonists with antidepressant and anxiolytic properties in the forced swim test (0.625e5 mg/kg and 0.625 mg/kg, respectively), the tail suspension test (0.625 mg/kg and 0.625 mg/kg, respectively), and in four plate test (0.625 mg/kg and 1.25e2.5 mg/kg, respectively) in mice. It has to be stressed that new compounds displayed higher activity than that of SB-269970, a reference 5-HT7R antagonist. Finally, the study provided valuable insight into the development of potential therapeutic agents for the treatment of CNS disorders.
Synthesis and α1-adrenoceptor antagonist activity of tamsulosin analogues
Sagratini, Gianni,Angeli, Piero,Buccioni, Michela,Gulini, Ugo,Marucci, Gabriella,Melchiorre, Carlo,Poggesi, Elena,Giardin, Dario
experimental part, p. 5800 - 5807 (2011/02/26)
Tamsulosin (-)-1 is the most utilized α1-adrenoceptor antagonist in the benign prostatic hyperplasia therapy owing to its uroselective antagonism and capability in relieving both obstructive and irritative lower urinary tract symptoms. Here we report the synthesis and pharmacological study of the homochiral (-)-1 analogues (-)-2-(-)-5, bearing definite modifications in the 2-substituted phenoxyethylamino group in order to evaluate their influence on the affinity profile for α1-adrenoceptor subtypes. The benzyl analogue (-)-3, displaying a preferential antagonist profile for α1A-than α1D-and α1B- adrenoceptors, and a 12-fold higher potency at α1A- adrenoceptors with respect to the α1B subtype, may have improved uroselectivity compared to (-)-1.
