7 research outputs found
Syntéza a studium reaktivity a biologické aktivity C5 substituovaných analog uracilu
Bibliografická identifikace: JmĂ©no a pĹ™ĂjmenĂ autora: RNDr. Lucie BrulĂková (roz. Spáčilová) Název práce: SyntĂ©za a studium reaktivity a biologickĂ© aktivity C-5 substituovanĂ˝ch analog uracilu Typ práce: doktorská PracovištÄ›: Katedra organickĂ© chemie PĹ™ĂrodovÄ›deckĂ© fakulty Univerzity PalackĂ©ho v Olomouci Ĺ kolitel: prof. RNDr. AntonĂn HolĂ˝, Dr.Sc., Dr.hc. mult. Ĺ kolitel-konzultant: doc. RNDr. Jan Hlaváč, Ph.D. Rok obhajoby práce: 2011 Abstrakt: PĹ™edloĹľená disertaÄŤnĂ práce je zaměřena na syntĂ©zu 5-substituovanĂ˝ch derivátĹŻ uracilu, jejich reaktivitu a studium biologickĂ© aktivity, pĹ™edevšĂm aktivity protinádorovĂ©. V Ăşvodnà části je vytvoĹ™en pĹ™ehled dosud popsanĂ˝ch vĂ˝sledkĹŻ vybranĂ˝ch C-5 substituovanĂ˝ch derivátĹŻ uracilu na poli jejich syntĂ©zy a studia biologickĂ© aktivity. Druhá část je vÄ›nována designu novĂ˝ch C-5 modifikovanĂ˝ch analog uracilu, vĂ˝voji a optimalizaci postupĹŻ vedoucĂch k cĂlovĂ˝m slouÄŤeninám, studiu biologickĂ© aktivity a odvozenĂ vztahu mezi strukturou a biologickou aktivitou (SAR studie). V tĂ©to části je prezentována syntĂ©za sĂ©rie derivátĹŻ odvozenĂ˝ch od 5- [alkoxy(4-nitrofenyl)methyl)]uracilu a 5-alkoxymethyluracilu a rozsáhlá SAR studie v závislosti na typu substituce methylenovĂ©ho mĹŻstku bezprostĹ™ednÄ› navázanĂ©ho do polohy C-5 a dále v závislosti na dĂ©lce alkoxylovĂ©ho Ĺ™etÄ›zce. V poslednà části...Bibliographical identification: Author's first name and surname: RNDr. Lucie BrulĂková (nee Spáčilová) Title: Synthesis, reactivity and biological activity of C-5 substituted uracil analogues Type of thesis: Ph.D. thesis Department: Department of Organic Chemistry, Faculty of Science, PalackĂ˝ University Olomouc Advisor: prof. RNDr. AntonĂn HolĂ˝, Dr.Sc., Dr.hc. mult. Advisor-consultant: doc. RNDr. Jan Hlaváč, Ph.D. The year of presentation: 2011 Abstract: The presented thesis is focused on the synthesis of various C-5 modified uracil analogues, the study of their reactivity and biological activity, especially cytotoxic activity. In the first part, the brief survey of described results for selected 5-alkoxymethyluracil analogues is performed. The second part of the presented thesis deals with the synthesis of novel uracil analogues modified at the C-5 position, the development and optimizing of procedure leading to the desired compounds, the study of biological activity and the evaluation of structure- activity relationship (SAR). This part presents the synthesis of a series of 5-[alkoxy(4- nitrophenyl)methyl)]uracil and 5-alkoxymethyluracil analogues and extended SAR studies depending on a substitution of metylene bridge directly attached at the C-5 position as well as alkoxy chain length. The last part of...Katedra organickĂ© chemieDepartment of Organic ChemistryPĹ™ĂrodovÄ›decká fakultaFaculty of Scienc
Synthesis, reactivity and biological activity of C5 substituted uracil analogues
Bibliographical identification: Author's first name and surname: RNDr. Lucie BrulĂková (nee Spáčilová) Title: Synthesis, reactivity and biological activity of C-5 substituted uracil analogues Type of thesis: Ph.D. thesis Department: Department of Organic Chemistry, Faculty of Science, PalackĂ˝ University Olomouc Advisor: prof. RNDr. AntonĂn HolĂ˝, Dr.Sc., Dr.hc. mult. Advisor-consultant: doc. RNDr. Jan Hlaváč, Ph.D. The year of presentation: 2011 Abstract: The presented thesis is focused on the synthesis of various C-5 modified uracil analogues, the study of their reactivity and biological activity, especially cytotoxic activity. In the first part, the brief survey of described results for selected 5-alkoxymethyluracil analogues is performed. The second part of the presented thesis deals with the synthesis of novel uracil analogues modified at the C-5 position, the development and optimizing of procedure leading to the desired compounds, the study of biological activity and the evaluation of structure- activity relationship (SAR). This part presents the synthesis of a series of 5-[alkoxy(4- nitrophenyl)methyl)]uracil and 5-alkoxymethyluracil analogues and extended SAR studies depending on a substitution of metylene bridge directly attached at the C-5 position as well as alkoxy chain length. The last part of..
Polymer-Supported Synthesis of Various Pteridinones and Pyrimidodiazepinones
In this report, we employed the solid-phase synthetic approach to prepare variously substituted dihydropteridinones, tetrahydropyrrolopteridinones, and pyrimidodiazepinones, using a versatile building block-4,6-dichloro-5-nitropyrimidine. All these compounds are pharmacologically significant scaffolds of the great importance of medicinal chemists. The fast and efficient synthetic methodology is highly desirable for defining their structure-activity relationship (SAR) and optimizing pharmacokinetic properties. Our research efforts utilize simple synthetic methods to generate a library of analogues for future SAR studies. The efficiency of our approach was exemplified in various pteridinones as well as pyrimidodiazepinones
Bicyclic N -dihalocyclopropylamide derivatives as precursors of nitrogen-containing fused polycyclic systems
International audienceExamples of carbon–carbon bond-forming cyclisation reactions, involving allyl cations generated by the thermal ring-opening of halocyclopropanes, have been scarcely reported. In this contribution, we are describing the results of a study conducted with N-dihalocyclopropylamide substrates, designed as precursors of cyclic iminium intermediates that were aimed at participating in intramolecular reactions with electron-rich aromatic groups. Competitive side-reactions were identified, and access to the desired polycyclic products was carefully evaluated. The results were found to be strongly dependent on the substitution pattern of the nucleophilic aromatic moieties, as well as on the sizes of the rings of the target products. In spite of the rather moderate yields generally obtained, this approach represents a particularly short and inexpensive route to various interesting nitrogen-containing polycyclic systems, namely benzoindolizidine, benzoquinolizidine, piperidinobenzoazepane and azepanoisoquinoline compounds