|
|
Synthesis of alkylsulfanyl substituted quinoxaline-2,3-dicarbonitriles and corresponding tetraquinoxalinoporphyrazines
Suchan, Daniel ; Zimčík, Petr (advisor) ; Kučerová, Marta (referee)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACEUTICAL CHEMISTRY AND DRUG CONTROL Name: Daniel Suchan Supervisor: Doc. PharmDr. Petr Zimčík Ph.D This work was focused on the preparation of 6,7-bis(tert-butylsulfanyl)quinoxaline- 2,3-dicarbonitrile as the precursor for tetra(2,3-quinoxalino)porphyrazine. This type of macrocyclic planar compounds with characteristic photophysical and photochemical properties has been reported only scarcely till this time and no derivatives substituted with heteroatom linkages have been reported yet. The first effort involved nucleophilic substitution of bromines in 6,7- dibromoquinoxaline-2,3-dicarbonitrile by tert-butylsulfanyl group. After series of unsuccessful attempts with thiolate under different reaction conditions, I've focused on alternative way. In the beginning, the alternative approach was tested on the synthesis of a model compound - quinoxaline-2,3-dicarbonitrile. It was obtained from benzene-1,2- diamine by condensation with oxalic acid, followed by chlorination with thionylchloride and finished by cyanation with KCN and benzyltrimethylamonium-chloride as activator. The synthesis of the target compound based on 4,5-bis(tert-butylsulfanyl)benzene-1,2- diamine ran similarly to the model reaction except the...
|
|
|
Synthesis, biological evaluation and in silico study of 7-MEOTA-donepezil inhibitors of cholinesterases
Čábelová, Pavla ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Pavla ábelová Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Supervisor specialist: PharmDr. Jan Korábe ný, Ph.D. Title of diploma thesis: Synthesis, biological evaluation and in silico studies in the series of novel 7-methoxytacrine-donepezile like compounds Alzheimer's disease (AD) is an irreversible neurodegenerative disorder of the brain characterized clinically by loss of memory, deterioration of activities of daily living and cognition. The pathological hallmarks of AD include neuritic plaques composed of extracellularly stored fibrils of amyloid- peptide, intracellular deposits of hyperphosphorylated tau and neurotransmitter deficits. The aim of the study was to design and synthesize 7-methoxytacrine-donepezil-like compounds as potential inhibitors of acetylcholinesterase (AChE, EC 3.1.1.7) and butyrylcholinesterase (BChE, EC 3.1.1.8). New compounds consist of 7-methoxytacrine representing less toxic derivative of tacrine and benzylpiperazine moiety corresponding to donepezil fragment. To determine the potential of new derivatives, AChE and BChE inhibitory activities of the new molecules were assessed in vitro according to the method of Ellman et al....
|
|
|
Synthesis of azaphthalocyanines bearing one 2,6-di(tert-butyl)phenol substituent
Lásková, Miroslava ; Zimčík, Petr (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department Department of Pharmaceutical Chemistry and Drug Control Candidate Miroslava Lásková Supervisor Doc. PharmDr. Petr Zimčík, Ph.D. Title of Thesis Synthesis of azaphthalocyanines bearing one 2,6-di(tert-butyl)phenol substituent In this work, azaphthalocyanines (AzaPc) bearing one 2,6-di(tert-butyl)phenol substituent were synthesized. Phenolic OH in this moiety is a weak donor for intramolecular charge transfer (ICT). However, this group can be ionized in basic media and the resulting phenolate anion is very strong donor. This was expected to cause ICT and quench fluorescence of this compound. The precursors for AzaPcs are substituted pyrazine-2,3-dicarbonitriles. They were prepared via one- step reaction of 5,6-dichloropyrazine-2,3-dicarbonitrile with 2-methylpropane-2-thiolate, respectively octanethiolate or via two-step reaction of 5,6-dichloropyrazine-2,3-dicarbonitrile with 2,6-di(tert- butyl)phenolate followed by nucleophilic substitution by 2-methylpropane-2-thiolate, respectively octanethiolate. Another precursor was prepared via reaction of glyoxylic acid with diaminomaleonitrile followed by chlorination with phosphoryl chloride and by subsequent nucleophilic substitution by 2,6- di(tert-butyl)phenolate. Resulting...
|
|
|
Design and synthesis of rutaecarpine analogs as potential cytotoxic agents for cancer chemotherapy treatment
Pešek, Tadeáš ; Kučerová, Marta (advisor) ; Opletalová, Veronika (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Student: Tadeáš Pešek Supervisor: PharmDr. Marta Kučerová, Ph.D., Charles University in Prague, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Thesis Title: Design and synthesis of rutaecarpine analogs as potential cytotoxic agents for cancer chemotherapy treatment Cancer is a progressive multifactorial collection of diseases that causes disorders and decreases quality of life of patients and in some cases results in death. Cancer can affect people of all ages, sexes and races and can be diagnosed in tissues of whole body. It is the second leading cause of death in the world after cardiovascular disorders. There are many ways how to treat cancer and they variy with each type of cancer. Nowadays treatment of cancer is based on surgery, chemotherapy, radiotherapy, biological treatment, immunotherapy and hormonal therapy. Chemotherapy represents the basis of cancer cure and is often used in combination with other approaches for tumour treatment and maximal effect of therapy and to prevent and cure metastases. Chemotherapy consists of cytotoxic agents that induce apoptosis by various pathways. These drugs interfere with cell cycle of all body cells but, in...
|
|
|
Amidoximes as intermediates for the synthesis of potential drugs
Katirtzi, Anastasia ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Pharmaceutical Analysis Student: Anastasia Katirtzi Supervisor: Assoc. Prof. RNDr. Veronika Opletalová, Ph.D. Title of Diploma Thesis: Amidoximes as intermediates for the synthesis of potential drugs The current thesis is focused on the O-acylation of pyrazine amidoximes and their cyclization to the corresponding 3,5-disubstituted- 1,2,4-oxadiazoles. 5-unsubstituted and 5-butylpyrazine amidoximes were acylated by acetic anhydride, trimethylacetic anhydride and 2,3-pyrazinecarboxylic anhydride as acylating agents in toluene. Formation of oxadiazoles was achieved in xylene, using acetic anhydride for acylation. Identification of the products was done by melting points, NMR and IR spectra, and their purity was proved by elemental analysis Furthermore, amidoximes and their derivatives were subjected to biological assay in order to evaluate their in vitro antifungal and antibacterial properties. Unfortunatelly, amidoximes and 1,2,4-oxadiazoles were inactive. For the esters, biological results will be available later.
|
|
|
Pyrazine derivatives as potential drugs IV
Janoutová, Alena ; Zitko, Jan (advisor) ; Kučerová, Marta (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Author: Alena Janoutová Supervisor: PharmDr. Jan Zitko, PhD. Title of diploma thesis: Pyrazine Derivatives as Potential Antituberculosis Drugs IV Drug research, potentially effective against tuberculosis, progress already for several years in the Department of Pharmaceutical Chemistry and Drug Control Faculty of Pharmacy in Hradec Králové. This study is focused on new derivatives of pyrazinamide (PZA) prepared as potential antituberculars. PZA itself is a well-established first-line antitubercular agent and a constituent of all basic tuberculosis treatment regimens. The design of final compounds was based on the previously synthesized 5-alkylamino-N-phenylpyrazine-2-carboxamides1, which possessed promising in vitro antimycobacterial activity with MIC ranging from 0.78 to 3.13 µg/mL. The object of this study was to test the activity of derivatives with alkylamino chain modified with terminal phenyl, hydroxyl or methoxy group. Final compounds were prepared by nucleophilic substitution of chlorine with respective amines in refluxing EtOH. Reaction yields, after all purification steps, were 58-87%. Compounds were characterized by 1 H and 13 C NMR, IR, elementary analysis and...
|
|
|
Acetylpyrazin-thiosemicarbazone analogues as potential drugs
Heczková, Jana ; Opletalová, Veronika (advisor) ; Kučerová, Marta (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Chemistry and Drug Control Candidate Mgr. Jana Heczková Consultant Doc. RNDr. Veronika Opletalová, Ph.D. Title of Thesis Acetylpyrazin-thiosemicarbazone analogues as potential drugs In the theoretical part of this thesis new findings on antifungal and antibacterial effects of thiosemicarbazones published in 2005 - 2012 were described. Thiosemicarbazones have a very broad range of antimicrobial activity, their effects are in many cases comparable or even better than already used pharmaceuticals. In the experimental part, the preparation procedures of thiosemicarbazones were described and following 7 compounds were prepared: (2E)-2-[1-(pyridine-2-yl)ethylidene]hydrazinecarbothioamide (2E)-2-[1-(pyridine-3-yl)ethylidene]hydrazinecarbothioamide (2E)-2-[1-(pyridine-4-yl)ethylidene]hydrazinecarbothioamide (2E)-2-[1-(2-hydroxyphenyl)ethylidene]hydrazinecarbothioamide (2E)-2-(2-hydroxybenzylidene)hydrazinecarbothioamide (2E)-2-[1-(2-hydroxyphenyl)ethylidene]-N,N-dimethylhydrazinecarbothioamide (2E)-2-(2-hydroxybenzylidene)-N,N-dimethylhydrazinecarbothioamide All prepared thiosemicarbazones were characterized by melting point, IR and NMR spectra. Purity was verified by elemental analysis. The...
|
|
| |
|
|
Synthesis of Precursors for Biologically Active Lactones II
Finková, Lenka ; Kučerová, Marta (advisor) ; Opletalová, Veronika (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Drug Control In the theoretical part of the diploma paper there are summarized antiviral effects of butenolides isolated from natural resources as well as substances obtained by synthesis. Methyl-(E)-2,3-dibromacrylate has been synthesized within the scope of the experimental work as a precursor for methyl-(E)-2-brom-5-subst.phenylpent-2-en-3- ynoates which have been obtained by Sonogashira coupling with different alkynes. Syntheses of some derivates have been optimized by modification of reaction conditions. Methyl-(E)-2-brom-5-subst.phenylpent-2-en-3-ynoates can be used as starting compounds for synthesis of potential biological active lactones.
|
|
|
Synthesis of Precursors for Biologically Active Lactones I
Bémová, Hana ; Kučerová, Marta (advisor) ; Zimčík, Petr (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Kralove Department of Pharmaceutical Chemistry and Drug Control SYNTHESIS OF PRECURSORS FOR BIOLOGICALLY ACTIVE LACTONES I. Diploma Thesis Hana Bemova A number of unsaturated five membered lactones from the family of 2,5-dihydrofuran-2- ones exert high biological activity, effecting cytotoxic, antifungal or antiviral, for example. The search of this diploma thesis resumes synthetic derivates of 2,5-dihydrofuran-2-ones with antineoplastic activity. Within this project two novel methyl (Z)- and two methyl (E)-5-aryl-2-brompent-2-en-4- ynoates were prepared by Sonogashira couplings methyl dihalogenpropiolates (E- and Z-isomers were developed by bromination of methyl propiolate) with arylethynes - phenylacetylene and 4ethynylN,Ndimethylaniline. Apart from the side product of homocoupling, β-monoalkynylated products were obtained in these reactions. A dialkynylated product was isolated in high yield (about 90 %) from the reaction with double phenylacetylene. All prepared substances can serve as precursors for various other coumpounds. The acids prepared by hydrolysis of methyl (E)-5-aryl-2-brompent-2-en-4-ynoates will be used for the lactonization into 5-alkyliden-2,5-dihydrofuran-2-ones. The target compounds containing group of γ-butyrolactone will...
|
guest ::
RSS feed.