Vol. 22 No. 1 (2024)

Pyrrolo[2,3-c]pyridines (6-azaindoles) are the most promising nitrogen-containing heterocyclic compounds in the field of drug development. Exhibiting extraordinary versatility as pharmacophores, they are widely used in the development of kinase inhibitors, antiproliferative agents, and as potential therapeutic agents for the treatment of various diseases, including cancer and Alzheimer’s disease. A large number of works focusing on new methods and approaches in the synthesis of 6-azaindoes, as well as on the study of their biological activity, have been published worldwide. In our review, we tried to classify all currently known strategies for the construction of the 6-azaindole core, which were published within the last 15 years, the chemical diversity of the derivatives obtained, and their therapeutic potential in the context of medicinal chemistry. We hope that this work will generalize and facilitate the understanding of the strategy for the synthesis of pyrrolo[2,3-c]pyridines, as well as help scientists in their further research in the direction of 6-azaindoles.

Nanotechnology can be used to treat a number of diseases, which are currently the main cause of death in the world, and allow to achieve the desired therapeutic effect for the patient. This mini-review focuses on the analysis of scientific literary sources dealing with the application of nanotechnology in the immunotherapy of diseases and covers the period from 2016 to 2022. In particular, it provides an overview of recently discovered nanotechnologies (including immunomodulatory nanosystems) used for the prevention and treatment of various diseases, including cancer, infectious, inflammatory, and autoimmune diseases. The review also discusses the role of nanosystems in cancer immunotherapy. Additional attention is paid to nanomaterials with new structures, properties, and functions, which are used in the modern practice of treating viral and bacterial infections. A part of the paper is devoted to nanoparticles that enhance the effect of immunosuppressive cells in the treatment of inflammatory and autoimmune diseases. The analysis performed clearly demonstrates the relevance of nanotechnologies for the use in the immunotherapy of diseases. We hope it will allow researchers to identify new areas for using nanoparticles in the treatment of diseases of various etiologies.

Growing evidence suggests that dipeptidyl peptidase 4 (DPP4) inhibitors, in addition to their role in improving glycemic control, help to reduce endothelial dysfunction and have hypolipidemic, anti-atherosclerotic, antitumor, antiviral, and neurotropic properties. This multi-target property may be one of the reasons for repurposing therapeutic treatment strategies with existing agents and the basis for finding new agents to inhibit this target. Based on the structural prerequisites and the evolutionary path of creating DPP4 inhibitors, an inhibitory (R)-β-aminoamide base was used as the basis for constructing potential candidates. It contained a substituted piperazine-2-one derivative and (S)-pyrrolidine-2-carbonitrile fragment, as well as phenyl and diphenyl rings, which were additionally saturated with substituents of various electronic structures, in position 4 of the β-aminoamide chain. The construction of the molecules was carried out taking into account the correspondence of chiral centers to combinations of chiral chains at the DPP4 binding site to possibly prevent a decrease in the inhibitory activity. In silico assessment of the “drug-likeness” and pharmacokinetic profile of the group of compounds studied showed that it had favorable characteristics and could be recommended for further molecular docking in order to predict the likely inhibition of the catalytic activity of DPP4. According to the results of docking, molecules with a moderate and high affinity were found. A detailed analysis of the resulting complexes showed that only nine compounds had a binding mode similar to classical inhibitors. According to the calculated array of values and analysis of the results of docking among the derivatives tested, a hit compound was found as a promising DPP4 inhibitor.

A practical and convenient method for synthesizing nicotinic acid and nicotinamide with the trifluoromethoxy group in position 5 of the ring has been developed. A series of related compounds, for example, nicotinic aldehyde and nicotinic alcohol, have been synthesized. It has been shown that 3-bromo-5-trifluoromethoxypyridine is a convenient and efficient synthon for palladium-catalyzed coupling reactions. The trifluoromethoxy group has been found to be remarkably stable against hydroiodic acid in contrast to the methoxy group.

The use of the cholinesterase enzyme as a component of the analytical system has made it possible to develop a new kinetic-spectrophotometric method, which is alternative to the pharmacopoeial method, for determining the quaternary ammonium salt – ethonium in the substance and a dosage form. This method is characterized by high sensitivity and specificity, and is relatively cheap. The relative standard deviation of the procedure does not exceed 2.7 %, and the limit of quantification is 17 ng mL^–1.