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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...
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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...
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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...
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Pyrazine Derivatives as Potential Antituberculosis Drugs I.
Semelková, Lucia ; Doležal, Martin (advisor) ; Miletín, Miroslav (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Author: Lucia Semelková Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of diploma thesis: Pyrazine Derivatives as Potential Antituberculosis Drugs I. Tuberculosis is a serious infectious disease, which has been one of the most common causes of death around the world for a long time. Despite of WHO effort to find effective procedures for the treatment and the continuous development of new potential drugs, TBC is still a major global problem. The development and progress of the resistant forms of this disease is the main cause. Review of the tuberculosis, antitubercular therapy and modern antimycobacterial drugs were presented in the first part of the diploma thesis. The principles and application of microwave assisted synthesis are also described. Eight new compounds, i.e. substituted 3-amino-N-benzylpyrazine-2- carboxamides, were prepared. The products were characterized by 1 H, 13 C NMR and IR spectra; elementary analysis of all compounds was performed, compounds were characterized by the melting points, the log P and Clog P values were also calculated. The antitubercular, antifungal and antibacterial activity of compounds was examined.
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