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Synthesis of alkylaminoderivatives of phthalocyanines
Tomek, Ondřej ; Kopecký, Kamil (advisor) ; Opletalová, Veronika (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Student: Ondřej Tomek Supervisor: PharmDr. Kamil Kopecký, Ph.D. Title of diploma thesis: Synthesis of alkylaminoderivates of phthalocyanines The aim of my diploma thesis was the synthesis and the characterization of phthalocyanine alkylaminoderivates and the comparison of their photophysical and photochemical properties with similarly substituted azaphthalocyanines. I start with the synthesis of dialkylaminodichlorophthalonitrile by the substitution of tetrachlorophthalonitrile. Then I use these derivates of tetrachlorophthalonitrile for cyclotetramerization reaction. As a result of my work, I received only diethylaminosubstituted phthalocyanines with undesirable butoxy-substituents. I was not successful in the preparation of phthalocyanines substituted with cyclic amines by the used methods. The prepared compounds were characterized by using the standard spectral methods (UV-VIS, IR, 1 H NMR, 13 C NMR, mass spectra).
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Pyrazine derivatives as potential drugs III
Hošťálková, Anna ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Deriváty pyrazinu jako potanciální léčiva III. Tuberkulóza je problém v celosvětovém měřítku. Rostoucí počet nakažených lidí, vznik lékově rezistentních kmenů Mycobacterium tuberculosis a ko-infekce HIV vedly k naléhavé potřebě nových antituberkulotik. Tato diplomová práce referuje o současných léčivech používaných při léčbě tuberkulózy a některých nových potenciálních antituberkuloticích. Také bylo v rámci diplomové práce syntetizováno deset nových látek, derivátů anilidů kyseliny pyrazin-2-karboxylové, které byly charakterizovány jejich fyzikálními vlastnostmi a poté byla zkoušena jejich antimykobakteriální a antifungální aktivita in vitro. Abstract Pyrazine derivatives as potential drugs III. Tuberculosis is a health problem worldwide. The increasing number of infected people, emergence of drug resistant strains Mycobacterium tuberculosis and HIV co-infection have resulted in the urgent need for new antituberculosis drugs. This degree work reviews drugs used in current treatment for tuberculosis and some of new potential anti-tuberculosis drug candidates. Within the task of this work were also synthesized ten new compounds, derivatives of anilides of pyrazin-2-carboxylic acid, which were characterized by physical properties and then was assayed their antimycobacterial and antifungal activity in...
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Pyrazine Derivates as Potential Antituberculotic Drugs
Kačírek, Michal ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of rigorous thesis: Pyrazine derivates as potential antituberculotic drugs Author: Mgr. Michal Kačírek In this rigorous thesis the recherche was realized which was focused on recent incidence of tuberculosis in the world, the possibility o f present therapy and the new trends in therapy as well. This thesis dealt with synthesis of undocumented compounds in literature. The starting compound was 5-chloro-6-methylpyrazine-2,3- dicabronitrile. The compounds were developed by aminodehalogenational reaction, linked to alkyl descriptor across amino group, whereas side chains were anal ogously extended. It can be said that the product was developed by reaction of 5 -chloro-6- methylpyrazine-2,3-dicabronitrile with corresponding primary aliphatic amine. Final compounds were characterized by thaw point, TLC, elementary analysis, 1 H a 13 C NMR and IR. All compounds were liable in vitro testing on their biological activity - antimycobacterial, antifungal and antibacterial. In the group of antituberculosis test ing the activity grew up from the least to the most lipophility compound.
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Solubilisation systems for potential photodynamic compounds III.
Grandová, Milada ; Miletín, Miroslav (advisor) ; Kopecký, Kamil (referee)
This graduation thesis is engaged in searching for solubilisation systems for potentially photodynamically active substances. The effort was focused on fading of systems with the smallest particles, transparent or modestly opalescent with the acceptable cytoxicity. Three systems satisfying the requirements for transparency (and so the particle size) were found but only two systems were used further for the solubilization of the photosenzitizers, the third one did not conform to the cytotoxicity tests. Another aim was to find, whether the photosensitizers, while solubilized using the selected systems, will not precipitate and will not be aggregated and therefore they would be usable in cell culture tests. Both the systems complying with the cytotoxicity tests proved to be usable. Photosenzitizers emulsified in them did not embody the aggregation or precipitation of the system. Finally measurements of the particles size of the systems with emulsified photosenzitizers were performed.
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Synthesis of Pyrazincarboxylic Acid Derivates as Potential
Sedlák, Petr ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Title of diploma thesis: Synthesis of pyrazincarboxylic acid derivates as potential antituberculotics Tuberculosis is a disease with about 9 million new cases every year, about 1,7 million people are dying yearly. For several decades the same antituberculotics are used for treatment, but new strains of tuberculosis are appearing and resistance is growing. The old antituberculotics become to be ineffective. There is need to be new ones researched. Review of tuberculosis therapy and modern research were presented in this thesis. Nine novel derivates of acylamine pyrazinic acid and its esters were synthesized. Novel structures were characterized by melting points, TLC, IR, 1H and 13C NMR. This set was put through in vitro biological evaluation. Log P and Clog P were also calculated and were compared with novel synthesized structures.
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Synthesis of Zinc (II) Aryloxy Tetraquinoxalinoporphyrazines
Vůjtěch, Petr ; Zimčík, Petr (advisor) ; Kopecký, Kamil (referee)
A B S T R A C T Charles University in Prague Faculty of Pharmacy in Hradec Kralové Department of Pharmaceutical Chemistry and Drug Control Candidate: Mgr. Petr Vůjtěch Consultant: PharmDr. Petr Zimčík Ph.D. Title of Thesis: Synthesis of Zinc (II) Aryloxy Tetraquinoxalinoporphyrazines The aim of my master thesis was synthesis of tetra[6,7]quinoxalinoporhyrazine derivative (TQP). Advantage of TQP is bathochromic shift when compared to azaphthalocyanines (AzaPc), which is more appropriate for PDT. AzaPc and TQP derivatives are large planar and conjugated systems, which tend to form aggregates. The aggregation is unfavorable property of TQP derivatives that reduces the singlet oxygen quantum yield. The most effective strategy to increase the ratio monomer/aggregates involves the use of bulky substituents attached to the TQP periphery. That is the reason why I focused on synthesis of 2,3,11,12,20,21,29,30-octa(2,6-diisopropyphenoxy)-tetra [6,7]qinoxalinoporphyrazinato zinc(II). Alkoxides cannot be used for cycloteramerization of aryloxy derivatives due to the well-described transetherification problems. As was shown in my diploma thesis the best way to synthesis of aryloxy derivatives of AzaPc is reaction with Zn(quinoline)2Cl2 in a melt. That is why this method was applied also for TQP derivatives. Kinetic of...
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Derivatives of Rhodanine as Potential Antifungal Drugs
El Zein, Mariana ; Opletalová, Veronika (advisor) ; Kopecký, Kamil (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Mariana El-Zein Consultant: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Thesis: Derivatives of Rhodanine as Potential Antifungal Drugs Rhodanine (2-thioxo-1,3-thiazolidin-4-one) forms the basic skeleton of many biologically active substances and potential drugs. Antifungal properties of rhodanine derivatives have been studied since the early 1950s. Theoretical part of the thesis deals with mycoses and drugs that are currently used to treat them. The aim of the experimental work was to find suitable reaction conditions for Mannich reaction of (5Z)-5-(subst.)benzylidenes-2-thioxo-1,3-thiazolidin-4-ones with various amines. The attempts to prepare Mannich bases using diethylamine as the basic component were unsuccessful. (5Z)-5-benzylidene-3-(morpholin-4-yl-methyl)-2-thioxo-1,3-thiazolidin- 4-one was successfully obtained by treating (5Z)-5-benzylidene-2-thioxo-1,3-thiazolidin- 4-one with formaldehyde and morpholine in dimethylformamide. This compound was reported previously and exhibited antibacterial activity and acceptable toxicity. Hence, Mannich bases derived from (5Z)-5-arylalkylidene-2-thioxo-1,3-thiazolidin-4-ones deserve further attention as potential...
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Pyrazine derivatives as potential antimycobacterial drugs I.
Vobicková, Jana ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate: Jana Vobicková Supervisor: Prof. PharmDr. Martin Doležal, Ph.D. Title: Pyrazine derivatives as potential antimycobacterial drugs I. In this diploma thesis basic information on tuberculosis, its treatment and trends in the devolopment of new drugs were presented. There were synthetised seven esters of the 3-aminopyrazin-2-carboxylic acid. The CEM Discover microwave reactor with autosampler Explorer 24 which served to accelerate the reaction was used for synthesis. The series of prepared products was characterized by IR, 1 H NMR, 13 C NMR spectra and melting points. Log P and Clog P were calculated. Products were put through in vitro antimycobacterial activity.
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Amidoximes as synthetic intermediates and potential drugs I.
Horká, Michaela ; Opletalová, Veronika (advisor) ; Kopecký, Kamil (referee)
AMIDOXIMES AS SYNTHETIC INTERMEDIATES AND POTENTIAL DRUGS I. Michaela Horká Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control In the theoretical part of this diploma thesis, biological activities of amidoximes are resumed. They have been studied mainly as prodrugs that are reduced to active compounds - amidines. Some amidoximes reached clinical trials but due to their significant undesirable effects have not been developed further. Methodical part deals with various synthetic procedures for the preparation of amidoximes. In the frame of the experimental part, four 5-alkylpyrazine-2-carbonitriles were synthesized at first. Using hydroxylamine hydrochloride, the nitriles were converted to corresponding amidoximes: N'-hydroxy-5-propylpyrazine-2-carboximidamide N'-hydroxy-5-isopropylpyrazine-2-carboximidamide N'-hydroxy-5-pentylpyrazine-2-carboximidamide N'-hydroxy-5-hexylpyrazine-2-carboximidamide None of the obtained products have been reported yet. They were characterized by melting points, IR, NMR spectra. Their purity was checked by elemental analysis. The compounds were tested for antifungal and antibacterial activity but were found non-effective. This is probably due to the fact that in vitro their bioactivation...
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Synthesis of bisquaternary nonsymmetric acetylcholinesterase reactivators
Sopr, Stanislav ; Doležal, Martin (advisor) ; Kopecký, Kamil (referee)
Stanislav Sopr: PREPARATION OF BISQUARTERNARY NON-SYMETRIC ACETYLCHOLINESTERASE REACTIVATORS Abstract The acetylcholinesterase (AChE) reactivators cause the re-activation of AChE activity after inhibition by organophosphorus compounds (OP). Such OP inhibitors were formerly developed as pesticides, but they were further used as chemical warfare agents due to their extremely high inhibition of cholinesterases. In this diploma thesis, 18 novel AChE reactivators were prepared. Their ability to reactivate paraoxon-inhibited AChE was evaluated in vitro via Ellman's method and compared to 3 standard commercial compounds (pralidoxime, obidoxime and HI-6). Any newly prepared compound was superior to known standards at 10-4 mol/l concentration. However, three novel compounds were able to exceed reactivation ability of known standards at 10-6 mol/l concentration and one novel compound exceeded reactivation limit for further potential in vivo evaluation.
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