Parkinson's disease (PD) is a neurodegenerative disorder that affects millions of people worldwide. A key factor in the development of this disease is the deficiency of dopamine in the brain, which causes symptoms such as tremors, rigidity, and movement difficulties. The enzyme monoamine oxidase B (MAO-B) is involved in the breakdown of dopamine, so inhibiting its activity is an effective way to increase dopamine availability and alleviate the symptoms of PD. Although there are currently medications that can significantly relieve symptoms, they often cause side effects and do not slow the progression of the disease, highlighting the need for new and improved therapies.
The aim of this master's is the synthesis and evaluation of new thiazole derivatives as potential MAO-B inhibitors. The research involves a two-step synthesis of thiazole derivatives based on the modification of reaction conditions to improve yield and product purity. Our work was based on the two-step synthesis from the starting compounds 2,5-dibromothiazole and 2,4-dibromothiazole, exploring different reaction conditions to optimize yields and product purity. The synthesis was carried out using various catalysts, bases, solvents, and ligands, which were tested in different combinations. In this way, we precisely analyzed the influence of individual components on the reaction course. Among the various techniques used, microwave synthesis proved to be particularly effective. Microwave heating allowed for rapid, energy-efficient, and highly selective reactions, significantly contributing to increased yields and purity of the final products. This technique also enabled better control of the reaction conditions. In addition to microwave heating, we also examined other reaction conditions such as different temperatures, reaction times, and reagent concentrations, providing a comprehensive insight into the optimal conditions for the synthesis of thiazole derivatives.
In the course of this master's thesis, we successfully synthesized four thiazole derivatives with various substituents. The best results were achieved using 2,4-dibromothiazole as the starting compound. Some of the synthesized compounds exhibited inhibitory activity against MAO-B, with low IC50 values, indicating their potential as therapeutic agents for the treatment of Parkinson's disease.
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