| Summary: | Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Dpt. of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Jan Zitko Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of Doctoral Thesis: Derivatives of pyrazinecarboxylic acid as potential antituberculotics (synthesis and biological evaluation) This thesis deals with derivatives of pyrazine-2-carboxylic (POA) acid with potential antimycobacterial activity. In the theoretical part of the thesis there is a short description of tuberculosis (TB) disease, discussion of its epidemiology an associated risk factors of increasing resistance to fist-line antituberculars and the co-infection with HIV. Antituberculars used in clinical practice are described as well as the summary of new antituberculars under clinical trials is presented. Pyrazinamide (PZA) as one of the most important first-line antituberculars is in the focus of this thesis. Multiple up-to-date theories of PZA (POA) mechanism of action are described and discussed. Importantly, a summary of structural changes of PZA/POA attempted in the past to prepare new antituberculars is presented and the importance and relevance of individual structural changes is discussed. In the practical part of this thesis, 76 derivatives of PZA/POA were prepared, 68 of...
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