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Synthesis and in vitro evaluation of pyridinium type acetylcholinesterase inhibitors.
Kopečková, Anna ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title: Synthesis and in vitro evaluation of pyridinium type acetylcholinesterase inhibitors Author: Anna Kopečková Nerve agents are extremely toxic substances. As prophylactics against these compounds, reversible acetylcholinesterase (AChE) inhibitors are used in the Czech Army. The goal of the thesis was to synthesise new potential inhibitors and evaluate their in vitro inhibition activity. The compounds were designed as asymmetrical bisquaternary molecules. Their structure was derived from isochinoline and 4-benzylpyridine; these two molecules were connected with variable connecting linkages (5-12 carbons). The synthesis involved two steps. Reactions of both steps took place in acetonitrile at 70 řC. Afterwards, the compounds were purified and their identity was confirmed with NMR- analysis, mass spectrometry and elementary analysis. The Ellman's method was used for the inhibitory potential evaluation. Eight compounds were succesfully prepared. All of them showed promising inhibitory potential (IC50 values 10-7 -10-8 mol/l). The stronges inhibitors were compounds bearing heptylenic and decylenic connecting linkage (IC50 0,05 µM). The selecitivity towards AChE decreased with prolonging connecting linkage.
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Pyrazine Derivatives as Potential Antituberculosis Drugs II.
Tauchman, Marek ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Charles Univeristy in Prague, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Drug Control Author: Marek Tauchman Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title of Diploma Thesis: Pyrazine Derivatives as Potential Antituberculosis Drugs II. Tuberculosis still presents serious worldwide problem of today. The situation is complicated especially by increasing proportion of strains resistant to common antituberculotics. Therefore the need of a new compound active against mycobacterial causer of the disease is very actual. Synthesis of compounds derived from pyrazinamide, very effecitve anti-mycobacterial substance, is one of the perspective way of new drugs development. Department of Pharmaceutical Chemistry and Drug Control, Faculty of Pharmacy in Hradec Králové, beside others, deals with this problem in a long term. There were synthesized hundreds of compounds containing pyrazine core and they were tested to antimycobacterial activity. The target of this thesis is join this effort and contribute to increase the number of compound that has been studied for antituberculosis activity. At the beginning of thesis, there is a summary of facts about tuberculosis, such as incidence, patogenesis and cure. Next, there are informations about newly developed...
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Synthesis of Precursors for Biologically Active Lactones III.
Šipulová, Zuzana ; Kučerová, Marta (advisor) ; Kopecký, Kamil (referee)
OF DIPLOMA THESIS Synthesis of Precursors for Biologically Active Lactones III. Zuzana Šipulová Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control In the theoretical part of the diploma thesis, diseases caused by fungi (mycoses), their treatment and also antifungal and other effects of furan-2(5H)-one-containing agents are summarized. Methyl-(E)-2-brom-5-(2-nitrophenyl)pent-2-en-4-ynoate has been synthesized within the scope of the experimental work. Methyl-(E)-2-brom-5-phenylpent-2-en-4-ynoate has been also synthesized in the experimental work as a starting ester for methyl-(E)-2-(arylethynyl)-5-phenylpent-2-en- 4-ynoates which have been obtained via coupling with different alkynes. Syntheses of some derivates have been optimized by modification of reaction conditions. Methyl-(E)- 2-(arylethynyl)-5-phenylpent-2-en-4-ynoates can be used as starting compounds for synthesis of potential biological active lactones.
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Syntesis and modification of fluorescence quenching compounds II.
Dejnožka, Vojtěch ; Miletín, Miroslav (advisor) ; Kopecký, Kamil (referee)
This thesis focuses on the synthesis of intermediates suitable for cyclotertramerization of naphthalocyanine aza-analogues. The aim of this thesis was to find and optimize a problematic step of the synthesis of an important intermediate which preparation employing classical synthesis methods shown to be problematic. We tried to solve this problem by testing and application of microwave radiation on the reaction process. We tested various possibilities of reaction conditions and parameters during the experiments. The reaction mixture was subjected to various temperatures and variable time in the environment of microwave radiation. Thereby we succeeded in finding the way to the satisfactory synthesis of the intermediate with exactly defined period and conditions of reaction process in microwave reactor CEM Explorer - 24 position. We re-purified the prepared compound through column and we used it consequently for the preparation of the next step (product) within the scope of synthesis of intermediates for cyclotertramerization of naphthalocyanine aza-analogues. The last product was specified by IR and NMR spectra.
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Synthesis of Ortho-fused Heterocycles as the Precursors of Azaphthalocyanine Dyes
Gela, Petr ; Roh, Jaroslav (advisor) ; Kopecký, Kamil (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of inorganic and organic chemistry Candidate Mgr. Petr Gela Consultant PharmDr. Jaroslav Roh, Ph.D. Title of Thesis Synthesis of ortho-fused heterocycles as the precursors of azaphthalocyanine dyes Chemical compounds containing tetrazole in recent years display an unprecedented boom. They exhibit a wide area of implementation in many areas especially in the pharmaceutical industry. The tetrazole group in these compounds acts as a bioisosteric surrogate for the functional group of carboxylic acid mainly because of close physical and chemical properties. The most important drugs containing tetrazole are used in the treatment of hypertension. In presented work we focused on the conversion of the tetrazole cycle into a different heterocyclic compound. The tetrazole can be used to the formation of other heterocycles with different number of cycles and hetero atoms. Moreover, the newly formed cycle can be also part of ortho-condensed system. In this work, we delt with the reactions of 5-substituted tetrazole with 6-substituted 5-chloropyrazine-2,3-dicarbonitrile, resulting in corresponding [1,2,4]triazolo[4,3-a]pyrazin-5,6-dicarbonitrile. Eight new and previously undescribed compounds were prepared. Synthetised compounds were used as a...
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Binding of azaphthalocyanine on 5'-end of oligonucleotide - "click" chemistry
Křížová, Iveta ; Kopecký, Kamil (advisor) ; Švec, Jan (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Iveta Křížová Supervisor: PharmDr. Kamil Kopecký, Ph.D. Title of diploma thesis: Binding of azaphthalocyanine on 5'-end of oligonucleotide - "click" chemistry This diploma thesis is focused on synthesis of pyrazin-2,3-dicarbonitrile derivates that are substituted with alkylamine substituents in location 5 and 6. Then cyclotetramerization of these compounds to the final azaphthalocyanines was realized. Alkylamine substituents were chosen in the way, that bond on 5'-end of oligonucleotide with terminal alkyn modification could be performed according to Huisgen 1,3-dipolar cycloaddition. Azaphtalocyanine with one hydoxyl group was prepared and described. Preparation of intended structure with one azide group was unsuccessful. Azaphtalocyanines are characterized by important photophysical and photochemical properties. Therefor were these compounds characterized with NMR, IR and mass spectra. In section Theory was explained the principle of quenching of fluorescence, practical use of quenching and overview of up to date the most commonly used quencher of fluorescence. There is also comparing of their positive and negative properties and little bit outlining of properties...
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Pyrazine derivatives as potential drugs VII.
Janďourek, Ondřej ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Pyrazin derivatives as potential drugs VII. Ondřej Janďourek Tuberculosis is one of the biggest health problems in the world. The number of new cases is rising every day, especially in less developed countries. The other problem is drug resistant tuberculosis which is occurring more and more frequently. Consequently these circumstances lead to one solution - to find new compounds to treat this greasy disease. This work deals with synthesis of undocumented compounds in literature. The starting compound was 5-chloro-6- methylpyrazine-2,3-dicarbonitrile. The compounds were developed by aminodehalogenational reaction by substituted anilines. Final compounds were characterized by molecular weight, melting point, TLC, logP, elemental analysis, 1 H and 13 C NMR and IR. Compounds were tested in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial.
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Synthesis of aryloxyderivatives of azaphthalocyanines
Ficnerová, Dominika ; Kopecký, Kamil (advisor) ; Miletín, Miroslav (referee)
SYNTHESIS OF ARYLOXYDERIVATIVES OF AZAPHTHALOCYANINES Dominika Ficnerová Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control This work deals with the synthesis of aryloxyderivatives of azaphthalocyanines. The theoretical part discusses the characteristics, advantages, disadvantages and use different types of fluorophores. At the same time is divided into different groups according to their chemical structure. Methodology section describes the ways in which it is possible to prepare phthalocyanines azaanalogues and the work also briefly describes the properties and reactivity of these substances. In the experimental part of this work is described, which methods and procedures can be precursors for the preparation azaphthalocyanines prepare. It is also described how to proceed with the actual cyclization reaction, which can be prepared azaphthalocyanines. Products were characterized by melting point, NMR, and IR spectra. The cyclization reaction products were measured value of fluorescence and singlet oxygen production.
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Multi-temporal classification of agricultural crops using Sentinel-1
Kopecký, Kamil ; Štych, Přemysl (advisor) ; Mouratidis, Antonios (referee)
Multi-temporal classification of agricultural crops using Sentinel-1 Abstract This diploma thesis aimed on the exploration of the reflective behavior of individual agricultural crops during the vegetation season. Statistical analysis of agricultural crops was carried out on the basis of multi-temporal SAR C-band Sentinel-1 data. The crop's backscatter was observed during the year 2016. Classification rules were made from detected characteristics. Achieved knowledge was applied and crops separation was done. The result of separation was successful in class Maize. Spring and Winter grains was impossible to distinguish. The possible reasons of poor results are mentioned and further improvements are suggested. Keywords: SAR, C-Band, crops, object-based classification, SENTINEL-1
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Maps creation from image data of the Mars surface
Kopecký, Kamil ; Kolář, Jan (advisor) ; Čábelka, Miroslav (referee)
Spectral behavior of Mars altimetry Abstract The goals of this thesis are research of cartography of Mars and the problems connected with it. The second goal is the creation of the maps of Mars's surface and lastly the analysis of the surface elevation and its spectral behavior. Firstly, the thesis outlines the theoretical part which includes usage of reference bodies, coordinates systems, cartographic projections and prime meridian. Second, it features the methodical procedure of creating the maps and the analysis. Key words: map projection, image data, Mars surface, thematic maps
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