Download Dr. Balázs Volk e-mail: Title of the research

Dr. Balázs Volk
e-mail: [email protected]
Title of the research topic: Unexpected reactions of 2H-1,2,3-benzothiadiazine 1,1-dioxide
derivatives and their 3,4-dihydro counterparts
Description of the research topic:
Researchers of Egis Pharmaceuticals Plc have been performing studies on the synthesis and
pharmacological activity of 2H-1,2,3-benzothiadiazine 1,1-dioxide derivatives for several
years. In the course of the study aiming at the identification of new agents suitable for
prevention and treatment of the central nervous system disorders, aromatic nucleophilic
substitution, reduction, acetylation and alkylation reactions of these compounds have been
investigated at the Drug Substance Development Division.
The attempt to reduce the 3-acetyl moiety of 3-acetyl-7,8-dichloro-2-methyl-3,4-dihydro-2H1,2,3-benzothiadiazine 1,1-dioxide with LiAlH4 to a 3-ethyl moiety, led surprisingly to a ringcontracted thiazole derivative. The task of the PhD candidate will be the detailed
investigation of this base-mediated rearrangement including the extension to compounds
exhibiting various substituents of the benzothiadiazine ring system. Modern analytical
techniques (2D NMR, LC-MS, single-crystal X-ray) will also be used for the characterisation of
the new compounds. Not only preparative experiments but, in collaboration, quantum
chemical studies will also be performed for the deeper understanding of the mechanism of
the reactions.