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Synthesis of novel quinazoline derivatives as a potential multipotent therapeutics against Alzheimer's disease
Tošnerová, Daniela ; Karabanovich, Galina (advisor) ; Matouš, Petr (referee)
1 ABSTRACT Charles University, Faculty of Pharmacy in Hradec Králové Department of: Organic and Bioorganic Chemistry Mentor: Ing. Galina Karabanovich, Ph.D. Consultant: Ing. Barbora Svobodová, Ph.D. Student: Daniela Tošnerová Title of Thesis: Synthesis of novel quinazoline derivatives as a potential multipotent therapeutics against Alzheimer's disease Alzheimer's disease (AD) is a severe neurologic disorder. Current treatments only temporarily delay the progression of disease. The main limiting factor for developing of new therapeutic compounds is the simultaneous presence of multiple pathologies. Thus, a new group of potential drugs called multi-target directed ligands (MTDLs) emerged as an alternative option to combat AD. To this date, dozens of MTDLs have been published. As part of the experimetnal section of this thesis, a series of small molecules based on quinazoline scaffold was rationally designed with the intention to influence the activity of acetylcholinesterase, butyrylcholinesterase, monoamine oxidase A and B (MAO-A/MAO-B), and the GluN1/GluN2B subunit of N-methyl-D-aspartate receptor (NMDAR). Subsequently twenty-four new quinazoline derivatives were synthesized, and biologically evaluated. The overall results highlighted compound II-6h ((5E)-8-chlor-N-cyklohexyl-3-methyl-1-...
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