The design, synthesis and evaluation of new chemical entities for the development of drugs against cancer, diabetes, autoimmune disorders and infectious diseases

The main objective of the work described in this dissertation was to develop strategies for the design and synthesis of nitrogen heterocyclic systems for use as glycosidase and glycosyltransferase inhibitors and as protein synthesis inhibitors. Potential applications include use as antibacterial, antiviral, cancer, diabetes and autoimmune drugs. The heterocyclic ring systems include bicyclic trihydroxy-2-thiaquinolizidine ring systems, bicyclic iminopentitols, 2,5-bis(hydroxymethyl)-3,4-dihydroxypyrrolidines, and arylsubstituted 5-phenyl-thiomorpholine-3-carboxylic acids. The biological testing showed the specificity of bicyclic trihydroxy-2-thiaquinolizidine ring systems against glycosidases, and they have some antibacterial activity. The bicyclic iminopentitols containing the structural essence of a ribosyl cation in the form of a 1,4-dideoxy-1,4-iminopentitol can be used as scaffolds for the preparation of riboside hydrolase, phosphorylase and transferase inhibitors. The arylsubstituted 5-phenyl-thiomorpholine-3-carboxylic acid derivatives showed promising antibacterial activity. The ease of synthesis of these heterocyclic ring systems provides access to the development of completely new classes of glycosidase and glycosyltransferase inhibitors as well as new antibiotics.