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master's thesis
Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze
Zagreb: University of Zagreb, Faculty of Science, 2024. urn:nbn:hr:217:787739
Križan, Helena
University of Zagreb
Faculty of Science
Department of Chemistry

Institutional repository: Repository of the Faculty of Science

Cite this document

Križan, H. (2024). Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze (Master's thesis). Zagreb: University of Zagreb, Faculty of Science. Retrieved from https://urn.nsk.hr/urn:nbn:hr:217:787739

Križan, Helena. "Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze." Master's thesis, University of Zagreb, Faculty of Science, 2024. https://urn.nsk.hr/urn:nbn:hr:217:787739

Križan, Helena. "Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze." Master's thesis, University of Zagreb, Faculty of Science, 2024. https://urn.nsk.hr/urn:nbn:hr:217:787739

Križan, H. (2024). 'Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze', Master's thesis, University of Zagreb, Faculty of Science, accessed 21 December 2024, https://urn.nsk.hr/urn:nbn:hr:217:787739

Križan H. Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze [Master's thesis]. Zagreb: University of Zagreb, Faculty of Science; 2024 [cited 2024 December 21] Available at: https://urn.nsk.hr/urn:nbn:hr:217:787739

H. Križan, "Dizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze", Master's thesis, University of Zagreb, Faculty of Science, Zagreb, 2024. Available at: https://urn.nsk.hr/urn:nbn:hr:217:787739

Metadata
TitleDizajn i sinteza novih azaindolnih derivata kao mogućih inhibitora FYN kinaze
Title (english)The design and synthesis of novel azaindole derivatives as possible inhibitors of FYN kinase
AuthorHelena Križan
MentorDijana Pešić (mentor)
Committee memberInes Primožič (predsjednik povjerenstva)
Committee memberIva Juranović Cindrić (član povjerenstva)
Committee memberAleksandra Maršavelski (član povjerenstva)
Committee memberNikola Cindro (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Science
(Department of Chemistry)
Zagreb
Defense date and country2024-10-25, Croatia
Scientific / art field,
discipline and subdiscipline		NATURAL SCIENCES
Chemistry
Abstract
FYN kinaza je član obitelji SRC tirozin-kinaza, prepoznata kao prikladna meta za antitumorske lijekove te lijekove za neurodegenerativne bolesti, posebice Alzheimerovu bolest. Analizom literaturno dostupnih podataka o inhibitorima SRC obitelji kinaza racionalnim pristupom dizajnirani su, a zatim i sintetizirani, novi azaindolni derivati kao mogući inhibitori FYN kinaze. Na komercijano dostupan 4- klor-7H-pirolo[2,3-d]pirimidin uvedeni su 2-(trimetoksisilil)etoksimetilna zaštitna skupina i (2,4- dimetoksifenil)metanamin. Potom je uslijedila acilacija pomoću 3-metoksipropanoil-klorida i deprotekcija u trifluoroctenoj kiselini. Dobiveni azaindol poslužio je kao reaktant u Ullmanovoj reakciji, usporedno s fotoredoks reakcijom, koja se pokazala boljim pristupom. Pripravljeni spojevi pročišćeni su dostupnim kromatografskim tehnikama i okarakterizirani analitičkim metodama (UPLC-UV/MS, 1D i 2D NMR). U računalnom dijelu rada molekulskim uklapanjem uspoređeno je vezanje produkata, ATP- a i staurosporina u FYN kinaznu domenu te produkta dobivenog u fotoredoks reakciji u nekoliko kinaza SRC obitelji.
Abstract (english)
FYN kinase is a member of the SRC family of tyrosine kinases and has been recognized as a suitable target for anticancer drugs as well as drugs for neurodegenerative diseases, especially Alzheimer's disease. By analyzing the available data on inhibitors of the SRC family of kinases using a rational approach, new azaindole derivatives were designed, and then synthesized, as possible inhibitors of FYN kinase. 2-(trimethoxysilyl)ethoxymethyl protective group and (2,4-dimethoxyphenyl)methanamine were introduced to the commercially available 4-chloro-7H-pyrrolo[2,3-d]pyrimidine. This was followed by acylation using 3-methoxypropionyl chloride and deprotection in trifluoroacetic acid. The resulting azaindole served as a reactant in the Ullmann reaction, in parallel with the photoredox reaction, which proved to be the better approach. The prepared compounds were purified using available chromatographic techniques and characterized by analytical methods (UPLC-UV/MS, 1D and 2D NMR). In the computational part, molecular docking was used to compare the binding of the products, ATP, and staurosporine to the FYN kinase domain, as well as the product obtained in photoredox reaction to several kinases of the SRC family.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:217:787739
Study programmeTitle: Graduate university studies in chemistry; specializations in: Graduate university studies in chemistry
Course: Graduate university studies in chemistry
Study programme type: university
Study level: graduate
Academic / professional title: sveučilišni/a magistar/magistra kemije (sveučilišni/a magistar/magistra kemije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence In copyright icon
Created on2024-11-08 09:51:49