Project aim is to develop novel universal methods for the synthesis of polyheterocyclic pyrazole containing compounds and to investigate their structure and functional properties. The Project tasks are formed to cover the following: synthesis of intermediate pyrazole containing scaffolds from readily available starting compounds; synthesis and functionalization of target polyheterocyclic pyrazole containing compounds using novel organic synthesis methods such as Pd-catalyzed reactions, catalytic hydrogenation under high pressure, microwave assisted synthesis, inert reaction conditions, Grignard reagents, (pseudo)halogenation, metal induced cyclization, 1,3-dipolar cycloaddition, intramolecular cyclization and others; detailed and unambiguous structure analysis of novel polyheterocyclic pyrazole containing compounds applying modern methods of spectroscopic, spectrometric, X-ray and elemental analysis; investigation of optical and biological properties of novel polyheterocyclic pyrazole containing compounds at Kaunas University of Technology and in collaboration with researchers at Palacky University in Olomouc. Project results will be published in four publications in journals included into the Thomson Reuters database Web of Science and presented at four international conferences.
Project funding:
Projects funded by the Research Council of Lithuania (RCL), Projects carried out by researchers’ teams
Project results:
The pyrazole ring is an important structural motif present in numerous natural and synthetic biologically active compounds. Pyrazole derivatives have anti-inflammatory, anti-cancer, analgesic, antimicrobial and other beneficial properties. Some pyrazole derivatives are included in the composition of pharmaceuticals. For example, functionalized 1,5-diarylpyrazoles such as celecoxib are used as nonsteroidal anti-inflammatory drugs, while rimonabant is used to reduce obesity, formicin is a natural antibiotic. Due to its exceptional biological activity, the synthesis of pyrazole derivatives is widely studied and presented.
In the view of the lack of versatile methodologies to produce diverse pyrazole moiety bearing polyheterocycles and in a continuation of our research interest to develop experimental procedures to obtain yet unknown heterocyclic systems, in this Project we ought to pursue synthesis of novel pyrazole-containing polyheterocycles and investigate their functional properties. Synthesis of pyrazole moiety containing polyheterocycles and their functionalized derivatives is expected to give rise to versatile libraries of the compounds of potential biological interest.
The Poject idea is to explore synthetic access to novel polyheterocyclic systems containing pyrazole structural unit that could be the basis for the small libraries of novel functionalized organic compounds. Subsequent investigation of functional properties of such non-traditional pyrazole derivatives can result in discovery of novel biologically active compounds with interesting biomedical applications.
Therefore, the envisaged Project objective is to develop methods for the preparation of several types of novel polyheterocyclic compounds bearing pyrazole moiety, investigate their structure and assess their functional properties in collaboration with the researchers at partner institution.
During the entire duration of the Project, tasks related to systems such as 2,4,6-trisubstituted 2H-pyrazolo[4,3-c]pyridines, pyrrolo[2′,3′:4,5]pyrano[2,3-c]pyrazoles, pyrazolo[4?,3?:5,6]pyrano[4,3-c][1,2]oxazole, tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepines, pyrazole chalcones, etc., and the investigation of their biological and optical properties were investigated.
It was established that from such structurally simple and accessible compounds as 3-hydroxy-1H-pyrazoles or ethyl 1H-pyrazole-3(5)-carboxylates, by applying classical and modern organic synthesis reactions, it is possible to obtain various complex polyheterocyclic systems such as variously substituted 2H-pyrazolo[4,3-c]pyridines, pyrrolo[2′,3′:4,5]pyrano[2,3-c]pyrazoles, pyrazolo[4?,3?:5,6]pyrano[4,3-c][1,2]oxazoles, tetrahydro-4H-pyrazolo[1,5-a][1,4]diazepin-4-ones, pyrazole chalcones. Much attention has been paid to the detailed and unambiguous analysis of the structure of the compounds. Various nuclear magnetic resonance, high-resolution mass spectrometry, and infrared spectroscopy studies were used for this. Libraries of novel synthesized compounds were studied in cooperation with Project partners in order to determine their potential biological activity and photophysical properties. 7-Aryl-2-phenyl-2H-pyrazolo[4,3-c]pyridines demonstrated good photophysical properties and cytotoxicity against MV4-11, K562 and MCF-7 cancer cells. N-Aryl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-amines were photodynamically active against human cutaneous melanoma G361 cells and therefore could serve as a potential source of photosensitizing compounds with anticancer activities.
Based on the results obtained during the Project, five publications were prepared in journals with a citation index in the Clarivate Analytics Web of Science database. Also, the results of the Project were presented in thirteen international conferences.
Period of project implementation: 2020-06-11 - 2022-12-31
Project coordinator: Kaunas University of Technology
Project partners: Palacky University Olomouc
