Alexei Evgrafovich Favorskii was an outstanding organic chemist who left a great scientific legacy as a result of long time and fruitful work. Most of the theoretically and practically important discoveries of A.E.Favorskii were made in the chemistry of acetylene and its derivatives. Nowadays, the reactions discovered by him, which include acetylene – allene isomerization, the Favorskii and retro-Favorskii reactions, the Favorskii rearrangement and the vinylation reaction, are widely used in industry and in laboratory synthesis. This review summarizes the main scientific achievements of A.E.Favorskii, as well as their development in modern organic chemistry. Much consideration is given to acetylene – allene isomerization as a convenient method for the synthesis of methyl-substituted acetylenes and to the acetylene zipper reaction as a synthetic tool for obtaining terminal acetylenes. The review presents examples of the application of these reactions in modern organic synthesis of complex molecules, including natural compounds and their analogues.The bibliography includes 266 references.

An efficient approach towards the synthesis of 6-aryl-4-azidocinnolines was developed with the aim of exploring the photophysical properties of 6-aryl-4-azidocinnolines and their click reaction products with alkynes, 6-aryl-4-(1,2,3-1H-triazol-1-yl)cinnolines. The synthetic route is based on the Richter-type cyclization of 2-ethynyl-4-aryltriazenes with the formation of 4-bromo-6-arylcinnolines and nucleophilic substitution of a bromine atom with an azide functional group. The developed synthetic approach is tolerant to variations of functional groups on the aryl moiety. The resulting azidocinnolines were found to be reactive in both CuAAC with terminal alkynes and SPAAC with diazacyclononyne, yielding 4-triazolylcinnolines. It was found that 4-azido-6-arylcinnolines possess weak fluorescent properties, while conversion of the azido function into a triazole ring led to complete fluorescence quenching. The lack of fluorescence in triazoles could be explained by the non-planar structure of triazolylcinnolines and a possible photoinduced electron transfer (PET) mechanism. Among the series of 4-triazolylcinnoline derivatives a compound bearing hydroxyalkyl substituent at triazole ring was found to be cytotoxic to HeLa cells.

A new type of fluorogenic and fluorochromic probe based on the reduction of weakly fluorescent 4-azido-6-(4-cyanophenyl)cinnoline to the corresponding fluorescent cinnoline-4-amine was developed. We found that the fluorescence of 6-(4-cyanophenyl)cinnoline-4-amine is strongly affected by the nature of the solvent. The fluorogenic effect for the amine was detected in polar solvents with the strongest fluorescence increase in water. The environment-sensitive fluorogenic properties of cinnoline-4-amine in water were explained as a combination of two types of fluorescence mechanisms: aggregation-induced emission (AIE) and excited state intermolecular proton transfer (ESPT). The suitability of an azide–amine pair as a fluorogenic probe was tested using a HepG2 hepatic cancer cell line with detection by fluorescent microscopy, flow cytometry, and HPLC analysis of cells lysates. The results obtained confirm the possibility of the transformation of the azide to amine in cells and the potential applicability of the discovered fluorogenic and fluorochromic probe for different analytical and biological applications in aqueous medium.

The exploration and mapping of chemical space – the vast, multidimensional set of all small organic molecules – remains a central challenge in modern drug discovery. Traditional compound libraries and databases cover only a minute fraction of this space, limiting the discovery of novel, bioactive, and patentable chemotypes. Here, we present LEGION, an advanced workflow that integrates generative AI, AI-guided screening, and state-of-the-art cheminformatics tools within the Chemistry42 platform to enable comprehensive, large-scale exploration of chemical space around specific drug targets. Using NLRP3, a clinically relevant but structurally complex inflammasome protein, as a case study, LEGION combined ligand- and structure-based design strategies, in-house algorithms for 3D pharmacophore-aware scaffold extraction, and distinct library enumeration methods to identify over 34,000 unique scaffolds and generate approximately 110 million molecular structures. Iterative stages of 2D and 3D filtering, including machine learning and structure-based pharmacophore scoring, ensured the binding relevance and structural feasibility of the enumerated compounds. The resulting workflow proved effective for scaffold hopping, navigating unexplored regions of chemical space, and supporting intellectual property applications through the generation of structurally diverse and synthetically tractable structures. This work demonstrates, for the first time, an AI-enabled framework capable of both massive virtual screening and de novo compound generation, specifically tailored for extensive chemical space coverage around a biological target. LEGION establishes a new paradigm for the intelligent, scalable, and practical exploration of chemical space in drug discovery.