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Trisubstituted of 1,3,5-Triazines and their Effect on BACE1
1 , 1, 2 , 3 , 1, 4 , * 1 , * 1, 4
1  Institute of Neuroimmunology, Slovak Academy of Sciences, Dubravska Cesta 9, 845 10 Bratislava, Slovakia
2  Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 842 15 Bratislava, Slovakia
3  Department of Chemical Drugs, Faculty of Pharmacy, Masaryk University, Palackeho 1-3, CZ-612 42 Brno, Czech Republic
4  Department of Analytical Chemistry, Faculty of Natural Sciences, Comenius University, Ilkovicova 6, 84215 Bratislava, Slovakia
Academic Editor: Julio A. Seijas

Abstract:

Alzheimer's disease (AD) is a multifactorial neurological disease of unknown etiology that is associated with various risk factors. Various pharmacological approaches targeting distinct mechanisms have been investigated; however, they have not yet achieved disease-modifying effects. A series of nine trisubstituted 1,3,5-triazine-based derivatives was investigated as potential inhibitors of the β-secretase enzyme (beta-site amyloid precursor protein-cleaving enzyme 1, BACE1), one of the key enzymes in the pathogenesis of AD. Although triazine-based derivatives were recognized as BACE1 inhibitors, at a concentration of 10 µM the compounds demonstrated completely insignificant activity, only methyl (4-{4-[(2,3-dihydroxypropyl)amino]-6-[(4-sulfamoylbenzyl)amino]-1,3,5-triazin-2-yl}piperazin-1-yl)acetate and 4-({4-chloro-6-[(3-hydroxypropyl)amino]-1,3,5-triazin-2-yl}amino)benzenesulfonamide showed approximately 9% and 2% inhibition of BACE1 activity, respectively.

Keywords: Triazinylaminobenzenesulfonamides; Alzheimer’s disease; BACE1; Modulation
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