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Synthesis of substituted pyridines catalyzed by gold complexes
Matouš, Petr ; Pour, Milan (advisor) ; Klimešová, Věra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Petr Matouš Supervisor: Prof. RNDr. Milan Pour, Ph.D. Title of thesis: Synthesis of substituted pyridines catalyzed by gold complexes This work is focused on the synthesis of 3,4-disubstituted pyridine derivatives. MBS-protected propargylamine reacts with methyl propiolate to form 1,5-enyne that undergoes Sonogashira coupling with aryl iodides. Substituted enyne undergoes cyclization to tetrahydropyridine in the presence of tris(2-furanyl)phosphinegold(I)chloride. Deprotection leads to the preparation of substituted pyridines, which could serve as intermediates in organic synthesis or as potential biologically active substances. Keywords: gold catalysis, enyne cyclization, pyridine derivatives
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Tetrazoles as potential antituberculotics
Sander, Daniel ; Hrabálek, Alexandr (advisor) ; Klimešová, Věra (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate: Daniel Sander Consultant: Prof. PharmDr. Alexandr Hrabálek, CSc. Title of Thesis: Tetrazoles as potential antituberculotics The development of new antituberculotics has recently become the subject of interest of many pharmaceutical companies. The disease's pharmacotherapy is very demanding on the health system as well as pacient compliance, neither of which are on a sufficient level in the developing countries. As a result, multiresistant strains evolve and those, becoming practically untreatable, pose a serious threat even to the western civilization. Many pharmaceutical laboratories including the KAOCH of FaF are searching for new and more effective agents. One of the contributions to the field of research is also this diploma thesis. The subject of the thesis was the synthesis of series of substituted 1-aryl-1H-tetrazol- 5-thioles and a combination of three antituberculotically promising structural elements, 1-aryl-1H-tetrazole as a ground structure, an alkylated atom of sulfur connected to an electrondeficient carbon atom and an implementation of nitro groups. Final structures were reached through a few synthetic steps including both reactions known and new. The Hodgkins...
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Synthesis of imidazole derivatives with potential antimycobacterial activity
Cvejn, Daniel ; Klimešová, Věra (advisor) ; Špulák, Marcel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department Department of inorganic and organic chemistry Candidate Daniel Cvejn Supervisor Doc. RNDr. Věra Klimešová, CSc. Supervisor specialist Doc. Ing. Filip Bureš, Ph.D. Title of Thesis Synthesis of imidazole derivatives with potential antimycobacterial activity New substances with potential antimycobacterial actvity were predicted on the basis of literature research. The substance library includes 1-[2-(4-nitrophenyl)-1H-imidazol-4(5)- yl]alkanamines with or without CBz (benzyloxycarbonyl) protected alifatic amino group. Some of predicted derivatives were synthetized and minimal inhibition concentration (MIC) were then measured for four strains of Mycobacteria. Activity of predicted effective substances were compared with measured activity of the 1-[2-phenyl-1H-imidazol-4(5)- yl]alkanamines which do not possess nitro group. Structure activity relationships were also discussed. Keywords: imidazole, amines, antimycobacterial activity, Mycobacterium spp.
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Optimization of the Synthesis of 3-(4-Bromophenyl)-5-hydroxymethyl-5,6-dihydro- pyran-2-one
Krenk, Ondřej ; Pour, Milan (advisor) ; Klimešová, Věra (referee)
Treatment of cancer still requires searching of new antineoplastics. Studies of biological activity of natural produkts show, that wide spektrum of biological aktivity have α,β- unsaturated-δ-laktons as potential substance with cytostatik aktivity. Goal of this work is optimalization of synthesis of 3-(4-bromfenyl)-5-hydroxymethyl-5,6-dihydro-2H-pyran-2-one as analogue of biologically active substance with potential cytostatic effect against cell line of colorectal carcinoma. Results obtained from this work can be employed in the development of simplier and more economical synthesis of potential biologically active analogues of α,β- unsaturated-δ-lactones.
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Pyridine sulphides as antituberculotic active compounds
Sýkora, Lukáš ; Kuneš, Jiří (referee) ; Klimešová, Věra (advisor)
This diploma thesis is devoted to antituberculosis drugs research. A very briefly depicts of genus Mycobacterium, structure and composition of mycobacterial cell wall allowed here better process and determination of mechanisms of antituberculosis drugs targets. The synthesis selected derivates of pyridine sulfides: 4- (phenethylsulfanyl)pyridine-2-carbonitriles are the main aim of the diploma thesis. As well as a possible mechanism of action these substances is discussed. Thus a series of 4-(phenethylsulfanyl)pyridine-2-carbonitriles were synthesized. The structures were confirmed by IR spectra, NMR spectra and elementary analyses. Antimycobacterial activities these compounds were tested against Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium kansasii. None of prepared substances exhibited activity (against M. tuberculosis) comparable to clinical used antituberculosis drugs. Significant activity was observed (in compare with isoniazide) against M. kansasii and M. avium.
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Synthesis of Pyridazines by Ring Transformation Reaction
Budilová, Hana ; Pour, Milan (referee) ; Klimešová, Věra (advisor)
Charles University in Prague The Faculty of Pharmacy in Hradec Králové The Department of Inorganic and Organic Chemistry Candidate: Hana Budilová Supervisors: Doc. RNDr. Věra Klimešová, CSc. Prof. Dr. Rainer Beckert Title of Diploma Thesis: Synthesis of Pyridazines by Ring Transformation Reaction Pyridazines are heterocyclic compounds with two adjacent nitrogen atoms. There are a lot of synthetic approaches to get pyridazine. A number of specific transformations from other heterocyclic systems have been reported. This thesis deals with the synthesis of pyridazines by transformation of a four-membered heterocycle. Some new derivatives of 1-methyl-3-(4-tolylamino)-4-(4-tolylimino)-6-(4'- substituted-phenyl)-1,4-dihydropyridazines were synthesized by a ring transformation of four- membered 2 -1,2-diazetine. This compound was obtained by a cycloacylation reaction of methylhydrazine and bis-oxalimidoyl chloride. NMR and mass spectrometry confirmed structures of prepared compounds. 1-Methyl-3-(4-tolylamino)-4-(4-tolylimino)-6-phenyl-1,4-dihydropyridazine had been previously proven to possess antimycobacterial activity. The new derivatives were tested against Mycobacterium tuberculosis My 331/88, M. avium My 330/88, M. kansasii My 235/80 and M. kansasii 6 509/96. MIC values of these compounds range...
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Heterocyclic Compounds with Antimycobacterial Activity
Herzigová, Petra ; Klimešová, Věra (advisor) ; Potáček, Milan (referee) ; Pytela, Oldřich (referee)
The dissertation thesis belongs to the conception of the research of potential antimycobacterial compounds. The aim of this work is synthesis of sulphide pyridine derivatives and the relationship between structure and antimycobacterial activity. Within the framework of this Thesis, the 112 substituted derivates of 4-(subst. fenylalkylsulfanyl)pyridine-2-carboxylic acid were synthesized. Antimycobacterial activity of prepared substances has been tested under in vitro conditions against M. tuberculosis, and non-tuberculous mycobacteria M. avium and M. kansasii. The series of 4-(subst. phenethylsulfanyl)pyridine-2-carbothioamide (MIC 1-32 µmol/L) represents the most active substances (MIC 1-32 µmol/L). These derivates don't reach the activity used antituberculosis drugs against M. tuberculosis, but their activities against M. avium exceed that of isoniazid. The synthesis of new structures as potential antimycobacterial compounds forms the second part of Thesis. All synthesis is based on the use of bis- arylimidoyl chlorides of oxalic acid of as starting material. None of prepared new compounds don't display an interesting antimycobacterial activity.
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