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Synthesis of mouse CAR receptor analogs
Jirsová, Michala ; Špulák, Marcel (advisor) ; Palát, Karel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Ing. Michala Jirsová Supervisor: PharmDr. Marcel Špulák Ph.D. Title of thesis: Synthesis of mouse CAR receptor analogs This diploma thesis is focused on the synthesis of potential mouse CAR receptor agonists. Prepared compounds resulted from the structural changes of the template molecule TCPOBOP, when one of the two pyridine rings was removed from the structure and the phenyl moiety was substituted by both electron donor and acceptor functional groups. The syntheses were carried out on the basis of nucleophilic aromatic substitution starting from 2,3,5-trichloropyridine and appropriately substituted phenol. A series of twenty derivatives were prepared and their potential agonism/antagonism against the mouse CAR receptor was determined. Five of the tested substances showed a weak activation effect, furthermore, potential inhibitory activity was observed for the other three substances. These prepared compounds were tested on the HepG2 cell line, and their possible effect on selected bacteria, mycobacteria and fungal strains was also investigated to verify potential toxicity. Activity was observed in only one mycobacterial strain, Mycobacterium kansasii. Keywords: CAR receptor, pyridine,...
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Synthesis of mouse CAR receptor analogs
Jirsová, Michala ; Špulák, Marcel (advisor) ; Palát, Karel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Organic and Bioorganic Chemistry Candidate: Ing. Michala Jirsová Supervisor: PharmDr. Marcel Špulák Ph.D. Title of thesis: Synthesis of mouse CAR receptor analogs This diploma thesis is focused on the synthesis of potential mouse CAR receptor agonists. Prepared compounds resulted from the structural changes of the template molecule TCPOBOP, when one of the two pyridine rings was removed from the structure and the phenyl moiety was substituted by both electron donor and acceptor functional groups. The syntheses were carried out on the basis of nucleophilic aromatic substitution starting from 2,3,5-trichloropyridine and appropriately substituted phenol. A series of twenty derivatives were prepared and their potential agonism/antagonism against the mouse CAR receptor was determined. Five of the tested substances showed a weak activation effect, furthermore, potential inhibitory activity was observed for the other three substances. These prepared compounds were tested on the HepG2 cell line, and their possible effect on selected bacteria, mycobacteria and fungal strains was also investigated to verify potential toxicity. Activity was observed in only one mycobacterial strain, Mycobacterium kansasii. Keywords: CAR receptor, pyridine,...
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Synthesis of substituted arylguanidines as potential drugs VI.
Korábečný, Jan ; Palát, Karel (advisor) ; Macháček, Miloš (referee)
S Y N T H E S I S O F S U B S T I T U E D A R Y L G U A N I D I N E S A S P O T E N T I A L D R U G S V I . Author: Korábečný J. Tutor: Palát K. Dept. of Inorganic and Organic Chemistry Faculty of Pharmacy in Hradec Kralové Charles University in Prague, Czech Republic Background: High number of life imperilling mycotic infection carries with itself increased need of antifungal drugs and need of new substances. In usage of antimycobacterial drugs it is also the same. Increasing resistance of pathogenic organisms urges human population to search for new, effective drugs. Aim of study: The aim of my diploma work was to prepare series of substitued arylguanidines, mainly 1-[3-chlor-4- (alkylsulfanyl)phenyl]guanidines, which are tested on antifungal and antimycobacterial activity. Methods: 2-Chloro-1-(alkylsulfanyl)-4-nitrobenzenes were synthesized from 3,4-dichloronitrobenzene by custom methods; either by using of active copper or by using Pd2(dba)3 and Xantphos as catalyzers. The following reduction of nitrogroup to aminogroup was made by stannous chloride under nitrogen atmosphere. Rise of appropriate amonnium salts proceeded in reaction with gaseous dry hydrogen chloride, almost quantitatively. Reaction leading to rise of guanidines proceeded with cyanamide in the melt or ethanolic solution in autoclave at...
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Synthesis of substituted arylguanidines as potential drugs IX.
Vidrna, Ondřej ; Palát, Karel (advisor) ; Špulák, Marcel (referee)
Charles university in Prague Faculty of Pharmacy in Hradec Králové Department of Anorganic and Organic Chemistry Candidate: Ondřej Vidrna Supervisor: PharmDr. Karel Palát, CSc Title of diploma thesis: Synthesis of substituted arylguanidines as potential drugs IX. The increasing incidence of diseases caused by fungal and mycotic pathogens, many of which acquire resistance to available antifungal substances, causes the need for a search for new molecules inhibiting their growth. The worldwide research is focused on substances derived from guanidine which were found to be potentially active against many strains of fungi and bacteria. Faculty of Pharmacy in Hradec Králové has been researching these substances for many years. The aim is to get the most active compounds from the group of substituted arylguanidines and find a structure-activity relationships effect of these substances. In this study the seven previously undescribed molecules were synthesized: 1-(4- methyl-2-octylsulfanyl)phenylguanidinium nitrate, 1-(4-methyl-2-dodecylsulfanyl) phenylguanidinium nitrate, 1-(4-methyl-2-dodecylsulfanyl)phenyl-3,3-dimethylguanidine, octyl-(4-methyl-2-nitrophenyl)sulfide, 5-methyl-2-(octylsulfanyl)aniline, dodecyl-(4-methyl-2- nitrophenyl)sulfide and 5-methyl-2-(dodecylsulfanyl)aniline. Three of them were...
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Chalcones and their analogues as potential drugs VII
Švédová, Lucie ; Kučerová, Marta (advisor) ; Palát, Karel, st. (referee)
CHALCONES AND THEIR ANALOGS AS POTENTIAL DRUGS VII Lucie Švédová Department of pharmaceutical chemistry and drug control, Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Heyrovského 1203, 500 05 Hradec Králové, Czech Republic Abstract of the rigorous thesis: This synthetic thesis is focused on searching of potential drugs from the group of chalcone derivatives and links up to the long-term studied topic at our department. Antibacterial and antifungal effects are the main examined biological activities. In the theoretical part of this thesis there were arranged various antineoplastic effects of naturally occuring or synthetic chalcones. The bibliographic searches involve items from the last decade. Possible interventions on the level of control processes, proteosynthesis and nucleic acid synthesis, influence on mitosis, apoptosis and the P-glycoprotein and the action on angiogenesis and cancer invasivity were summarized. In addition antioxidant activity and other mechanisms of chemoprevention were introduced as well. Different methods of chalcone synthesis were summed up in conclusion. In the frame of the experimental part substituted derivatives and heterocyclic analogs of chalcones were synthetized by means of condensation reaction. All the synthetic products were characterized by...
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Synthesis of substituted arylguanidines as potential drugs VII.
Bromand, Nasir ; Palát, Karel (advisor) ; Macháček, Miloš (referee)
Pathological fungi carry the ability to cause serious medical problems and moreover cause various diseases. Drug therapy and new active compounds against these medical problems are still being researched. The long-term objective is to uncover the active compounds at the Faculty of Pharmacy, Charles University. In our study, we synthesized 3-(4-bromophenyl)-1,1-diethylguanidine, and 2 novel compounds: 3-(4- dodecylsulfanylphenyl)-1,1-diethylguanidine and 3-(3-bromophenyl)-1,1- diethylguanidine. We also studied the oxidation of 1-(4- tetradecylsulfanylphenyl)guanidinium nitrate, thus, making it the third novel compound 1-(4-tetradecylsulfonylphenyl)guanidinium nitrate we synthesized.
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Acetylpyrazines as intermediates for the synthesis of biologically active derivative of pyrazine III.
Zobalová, Dana ; Opletalová, Veronika (advisor) ; Palát, Karel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Analysis Candidate Mgr. Dana Honcová-Zobalová Consultant RNDr. Veronika Opletalová, Ph.D. Title of Thesis Acetylpyrazines as intermediates for the synthesis of biologically active derivatives of pyrazine III. The rigorous thesis is aimed at the preparation of 5-alkylpyrazin-2-carbonitriles, 5-alkyl-2-acetylpyrazines and their thiosemicarbazones and N,N-dimethylthiosemicarbazones. N,N-dimethylthiosemicarbazone of acetophenone was prepared for comparison. Theoretical part deals with the structure and properties of thiosemicarbazones and their biological effects. The following compounds were prepared and characterized during experimental work: 5-isopropylpyrazin-2-carbonitrile 5-pentylpyrazin-2-carbonitrile 5-hexylpyrazin-2-carbonitrile 5-heptylpyrazin-2-carbonitrile 1-(5-isopropylpyrazin-2-yl)ethan-1-one 1-(5-pentylpyrazin-2-yl)ethan-1-one 1-(5-hexylpyrazin-2-yl)ethan-1-one 1-(5-heptylpyrazin-2-yl)ethan-1-one 1-(5-hexylpyrazin-2-yl)ethan-1-one thiosemicarbazone 1-pyrazin-2-ylethan-1-one N,N-dimethylthiosemicarbazone 1-(5-pentylpyrazin-2-yl)ethan-1-one N,N-dimethylthiosemicarbazone 1-(5-hexylpyrazin-2-yl)ethan-1-one N,N-dimethylthiosemicarbazone ...
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Calculations of parameters of biologically active compounds by the quantum mechanical methods.
Horáček, Ondřej ; Palát, Karel (advisor) ; Krátký, Martin (referee)
8 ABSTRACT The aim of this work is to calculate the parameters of substituted bases and chosen phenylguanidinium cations, earlier synthesized at the Department of inorganic and organic chemistry on the Faculty of Pharmacy CU in Hradec Králové, using quantum chemical methods. I solved chosen problem by using computer programs Gaussian 03W and Hyperchem 8.0.10. I used program Gaussian to optimize the molecules and calculate the energy of the HOMO and LUMO, total energy and the atomic partial charge using the Mulliken population analysis. I used programe HyperChem to calculate the Van der Waals molecular volume; Van der Waals molecular surface; logP; the molar refraction; solvent-accessible surface of the probe size 1.0 Å; 1.2 Å; 1.4 Å; 1.6 Å and the atomic partial charge using methods PEOE. All parameters of selected substituted phenylguanidines above have been successfully calculated, and listed in the tables in the chapter called results. The calculated results were discussed in chapter called discussion. The calculated parameters will be used for further correlations and QSAR studies that will help to understand the biological activity of substituted phenylguanidines and hence their effect on the human organism.
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