Th.--Sci. phys.--Grenoble 1, 1982. N°: 51.

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Thesis (Ph. D.)--University of Wisconsin--Madison, 1950. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 69-70).

Reproduction de : Thèse doctorat : Chimie : Reims : 2007. / Titre provenant de l'écran titre. Bibliogr. f.

In the early phases of drug design and development, scientists must overcome many challenges involved in identifying potential drug-like or lead-like compounds. This has led to the need of creating large sets of chemical data which will aid in improving the identification of pharmacophores and active compounds. Various scientific fields especially pharmacology, medicinal chemistry and biochemistry have begun to employ the use of computer sciences to aid in the screening for potential leads with more specificity with regards to drug-like compounds' or substances' bioactivity. The emphasis of this project was to create a database containing a collection of pyrazine compounds synthesized overtime in the Faculty of Pharmacy (Charles University, Hradec Kralove) with the aim of having anti-mycobacterium (and possible antibacterial and antifungal) activity, and further utilize this database to predict certain pharmacokinetic and bioavailability properties. This project seeks to demonstrate how certain molecular descriptors can be used as reliable chemoinformation to determine the likeliness or possibility of developing a lead-like or drug-like compound by utilizing computer software. An in-house database of 623 compounds saved in SMILES format was created and used in demonstrating quantitative...

In the early phases of drug design and development, scientists must overcome many challenges involved in identifying potential drug-like or lead-like compounds. This has led to the need of creating large sets of chemical data which will aid in improving the identification of pharmacophores and active compounds. Various scientific fields especially pharmacology, medicinal chemistry and biochemistry have begun to employ the use of computer sciences to aid in the screening for potential leads with more specificity with regards to drug-like compounds' or substances' bioactivity. The emphasis of this project was to create a database containing a collection of pyrazine compounds synthesized overtime in the Faculty of Pharmacy (Charles University, Hradec Kralove) with the aim of having anti-mycobacterium (and possible antibacterial and antifungal) activity, and further utilize this database to predict certain pharmacokinetic and bioavailability properties. This project seeks to demonstrate how certain molecular descriptors can be used as reliable chemoinformation to determine the likeliness or possibility of developing a lead-like or drug-like compound by utilizing computer software. An in-house database of 623 compounds saved in SMILES format was created and used in demonstrating quantitative...

Thèse doctorat : Chimie et Physico-Chimie Moléculaires : Nancy 1 : 2007. / Titre provenant de l'écran-titre.

In this study, the effect of a donor ligand on the stabilization of a carbonyl pyrazine tungsten complex was studied. The pentacarbonylpyrazinetungsten(0) complex could be formed from the photolysis of hexacarbonyltungsten(0) in the presence of pyrazine and could be isolated as crystalline solid. However, the complex was found to be unstable in solution, being converted to a bimetallic complex, (CO)5W(pyz)W(CO)5 and free pyrazine molecule. Two complexes exist in solution at equilibrium. The equilibrium constant could be determined by 1H-NMR spectroscopy and found to be 0.0396 at 25&deg / C. To test whether the introduction of a second pyrazine ligand might provide stability for the carbonyl-pyrazine-tungsten complex, W(CO)4(pyz)2 was attempted to be synthesized. The cis-W(CO)4(pyz)2 complex could be generated from the thermal substitution reaction of cis-W(CO)4(piperidine)2 with excess pyrazine in dichloromethane. However, this complex could not be isolated because of the lack of stability. The complex could only be identified by IR spectroscopy in solution. To stabilize the pentacarbonylpyrazinetungsten(0) complex, trimethylphosphite was introduced to the complex as a donor ligand. For this purpose, cis-W(CO)4[P(OCH3)3](thf), photogenerated from W(CO)5[P(OCH3)3] in tetrahydrofuran (thf), was reacted with pyrazine. The replacement of tetrahydrofuran with pyrazine (pyz) yielded cis-W(CO)4[P(OCH3)3](pyz). The complex could be isolated from the reaction solution and characterized by means of IR, 1H-, 13C-, 31P-NMR, and Mass spectroscopies. The introduction of P(OCH3)3 has proved that a donor ligand will strengthen the metal-pyrazine bond and thus stabilizes the complex. As a result of this stabilization, the complex could be isolated as the first example of tungsten pyrazine complexes that contain a donor ligand.

An overview of the flavour and fragrance industry has indicated that there is a great demand for flavours to have the natural, halaal and kosher status. This has opened the door for the increase in production of flavours by microbial means. Particularly with regards to pyrazine production, bacterial species such as Bacillus are commonly used. Although previous literature indicated that fungi are not as prominent pyrazine producers compared to bacteria, this study has indicated that mycelial fungi can be considered for the production of natural pyrazine flavours. Out of the 280 fungi screened, 45% showed pyrazine flavour production as indicated in chapter 2. This chapter also showed that the content of growth media can have a substantial influence on flavour production. For example, fungi grown in Cz-medium produced more of the caramel and chocolate flavours, compared to fungi that were grown in TSB, which produced more of the nutty, meaty and potato flavours. The green flavour was, however, prominent in both media, of which mostly members of the Aspergillus and Penicillium groups produced this flavour. Selected Penicillium species, including Penicillium rubrum and P. purpurogenum produced a green pepper odour that is indicative of the presence of methoxypyrazine. Chemical analytical methods as described in chapter 3 confirmed that Penicillium purpurogenum produced 2-methoxy-3-isobutylpyrazine (MIBP) and Penicillium rubrum produced both 2-methoxy-3-isobutylpyrazine (MIBP) and 2-methoxy-3,5/6-isopropylpyrazine (MIPP). Methoxypyrazines are high impact aroma chemicals that have a typical green pepper odour and a high market value. Due to the favourable characteristics of the Penicillium species in industrial fermentation processes (such as mass spore production and rapid colonization of substrates) and their ability to produce high value compounds, these fungi were selected for further studies. In order to explore the potential use of these fungi in an industrial application, the methoxypyrazines produced were quantified. Prior to quantitation, a solvent extraction method, using dichloromethane, was developed. Amongst the different pH parameters analysed acidified conditions showed the best results, where 69% MIPP and 97% MIBP were recovered from the liquid-liquid extraction and 76% MIPP and 99% MIBP were recovered from the solid-liquid extraction. Pyrazines quantified from the liquid-liquid extractions indicated that Penicillium rubrum produced 0.38 μg MIPP.L-1 and 0.88 μg MIBP.L-1, and Penicillium purpurogenum produced 0.88 μg MIPP.L-1 and 2.15 μg MIBP.L-1 (Chapter 4). Yields obtained from this study were not seen as feasible for the production of methoxypyrazines by the fungi on an industrial scale and, therefore, solid state fermentation was investigated as an option to improve the yields. Due to the availability of soy press cake as a by-product, as well as the variety of the amino acids present, it was selected as a possible substrate for pyrazine production. The results from this study, however, indicated that the nature of the substrate, such as the lipid content, fungal content and particle size of the soy press cake does not support fungal growth and makes pyrazine analyses problematic. Alternate methods of improving methoxypyrazine yields thus need to be found. A limiting factor is the lack of understanding of the metabolic pathway involved in pyrazine production by Penicillium species. By having this knowledge the fermentation process can be adapted accordingly for the optimal production of methoxypyrazines by these microorganisms. Additionally, substrates that contain the necessary precursors that are cost effective would contribute significantly in the development of an economically viable fermentation process for the production of methoxypyrazines by Penicillium species. / Dissertation (MSc)--University of Pretoria, 2010. / Microbiology and Plant Pathology / unrestricted

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Supervisor: Assoc. Prof. PharmD. Jan Zitko, PhD. Author: Marek Kerda Title of diploma thesis: Design, synthesis and biological evaluation of 2,3-disubstituted pyrazines This thesis deals with problem of tuberculosis. In a theoretical part are summarized information and knowledge about tuberculosis, nowadays epidemiology and drugs used in current treatment. There are also described drugs in the different stage of clinical trials and could be used for treatment of tuberculosis in the future. Searched information were used from accessible learning materials and in articles in online databases as Web of Science and PubMed. There are also summarized basic methods of computer design of new drugs. In practical part of this thesis was focus on novel inhibitor of prolyl-tRNA synthetase, which is based on structure of pyrazinamide. There was prepared in silico virtual library of pyrazine-based new potential ligands. Related docking to the structure of human prolyl t-RNA (pdb: 5VAD) and the bacterial version of this enzyme (pdb: 2J3M) and evaluation was performed in Molecular Operating Environment (Chemical Computing Group, Canada). From the results were predicted some of the relations between structure and activity. Virtual library of the...