DIRECT C-H/S-H COUPLING OF 2Н-IMIDAZOLE-1-OXIDES AND THIOPHENOLS IN THE SYNTHESIS OF PERSPEVTIVE AZAHETEROCYCLIC COMPOUNDS

The study was carried out with the financial support of the Russian Science Foundation as a part of a research project 20-43-01004

SUBSEQUENCE NUCLEOPHILIC FUNCTIONALISATION IN THE SYNTHESIS OF ARYLTHIOFLUORINATED IMIDAZOLES

The study was carried out with the financial support of the Russian Science Foundation as part of a research project 23-63-10011, https://www.rscf.ru/en/project/23-63-10011/

C-H/C-H COUPLING OF 4H-IMIDAZOLE-3 OXIDES WITH INDOLES IN THE SYNTHESIS OF BIFUNCTIONAL AZAHETEROCYCLIC DERIVATIVES

The study was carried out with the financial support of the Russian Science Foundation as a part of a research project 20-43-01004

Indolyl-Derived 4H-Imidazoles: PASE Synthesis, Molecular Docking and In Vitro Cytotoxicity Assay

The strategy of the nucleophilic substitution of hydrogen (SNH) was first applied for the metal-free C-H/C-H coupling reactions of 4H-imidazole 3-oxides with indoles. As a result, a series of novel bifunctional azaheterocyclic derivatives were obtained in yields up to 95%. In silico experiments on the molecular docking were performed to evaluate the binding possibility of the synthesized small azaheterocyclic molecules to the selected biotargets (BACE1, BChE, CK1δ, AChE) associated with the pathogenesis of neurodegenerative diseases. To assess the cytotoxicity for the synthesized compounds, a series of in vitro experiments were also carried out on healthy human embryo kidney cells (HEK-293). The leading compound bearing both 5-phenyl-4H-imidazole and 1-methyl-1H-indole moieties was defined as the prospective molecule possessing the lowest cytotoxicity (IC50 > 300 µM on HEK-293) and the highest binding energy in the protein–ligand complex (AChE, −13.57 kcal/mol). The developed compounds could be of particular interest in medicinal chemistry, particularly in the targeted design of small-molecule candidates for the treatment of neurodegenerative disorders. © 2023 by the authors.Ministry of Education and Science of the Russian Federation, Minobrnauka: 075-15-2022-1118, W03.31.0034; Russian Science Foundation, RSF: 20-73-10077The chemical design, synthesis and characterization of indolyl-derived 4H -imidazoles and in vitro studies were supported by the Russian Science Foundation (Project # 20-73-10077). The in silico studies were supported by the Ministry of Science and Higher Education of the Russian Federation (Ref. # 075-15-2022-1118, dated 29 June 2022). The synthesis of starting 4H -imidazole N -oxide substrates was supported by the Ministry of Science and Higher Education of the Russian Federation (Project # 14.W03.31.0034)

Metal-Free Eliminative C-H Arylthiolation of 2<i>H</i>-Imidazole N-Oxides with Thiophenols

A synthetic strategy based on reactions of cyclic imine oxides, namely 2H-imidazole 1-oxides, with thiophenols mediated by acetyl chloride was successfully applied as a convenient tool to obtain a series of novel azaheterocyclic molecules, including water-soluble hydrochloride forms. Optimized reaction conditions found herein for the nucleophilic substitution of hydrogen (SNH) in non-aromatic azaheterocyclic substrates via the “addition-elimination” (SNH AE) scheme enabled 15 arylthiolated 2H-imidazoles to be prepared in yields of up to 90%. The developed methodology discloses an original synthetic way to obtain numerous azaheterocyclic molecules, which are of interest in the field of medicinal chemistry and materials science