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National Repository of Grey Literature

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Preparation of Pyrazinamide Derivatives as Potential Antituberculotics (Study of Structure Activity Relationships) Semelková, Lucia ; Doležal, Martin (advisor) ; Malík, Ivan (referee) ; Nencka, Radim (referee) Charles University, Faculty of Pharmacy in Hradec Králové Department: Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Candidate: Mgr. Lucia Semelková Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Consultant: PharmDr. Jan Zitko, Ph.D. Title of Doctoral Thesis: Preparation of Pyrazinamide Derivatives as Potential Antituberculotics (Study of Structure Activity Relationships) This doctoral thesis is focused on search for novel pyrazinamide derivatives with potential antitubercular activity. The theoretical part summarizes issues connected with tuberculosis and its epidemiological situation along with factors (resistance and HIV co- infection) that complicate treatment of tuberculosis. A brief overview of antitubercular drugs used in current therapeutic regimens of tuberculosis is outlined. A single chapter is dedicated to pyrazinamide, which belongs to the first-line antitubercular drugs, and its possible mechanisms of action. The last part is focused on potential enzymatic targets of pyrazinamide derivatives. The practical part describes synthesis and biological evaluation of 112 pyrazinamide derivatives with modifications in amide moiety and position 3 on the pyrazine ring. First two series were derived from N-substituted 3-chloropyrazine-2-carboxamides, the third series... Detailed record

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