Polyfunctional building blocks are essential for the implementation of diversity-oriented synthetic strategies, highly demanded in small molecule libraries’ design for modern drug discovery. Acyl(imidoyl)ketenes are highly reactive organic compounds, bearing both oxa- and aza-diene moieties, conjugated symmetrically to the ketene fragment, enabling synthesis of various skeletally diverse heterocycles on their basis. The highlights of reactions utilizing acyl(imidoyl)ketenes are high yields, short reaction time (about several minutes), high selectivity, atom economy, and simple purification procedures, which benefits the drug discovery. The present review focuses on the approaches to thermal generation of acyl(imidoyl)ketenes, patterns of their immediate transformations via intra- and intermolecular reactions, including the reactions of cyclodimerization, in which either symmetric or dissymmetric heterocycles can be formed. Recent advances in investigations on mechanisms, identifications of intermediates, and chemo- and regioselectivity of reactions with participation of acyl(imidoyl)ketenes are also covered.

Pyrrolo[2,1-b][1,3]benzothiazoles are an important class of fused sulfur and nitrogen-containing heterocycles intensively studied in medicinal chemistry and pharmacology. In the present paper, a new synthetic approach to pyrrolobenzothiazoles is developed based on 1,4-thiazine ring contraction in 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones under the action of nucleophiles. The proposed approach works well with alkanols, benzylamine, and arylamines. The scope and limitations of the developed approach are studied. The synthesized pyrrolobenzothiazole derivatives represent an interest to pharmaceutics, since their close analogs show CENP-E inhibitory activity, interesting for the targeted cancer therapy development.

Acyl(imidoyl)ketenes are highly reactive heterocumulenes that enable diversity-oriented synthesis of various drug-like heterocycles. Such ketenes, bearing heterocyclic substituents, afford angularly fused pyridin-2(1H)-ones in their [4+2]-cyclodimerization reactions. We have utilized this property for the development of a new synthetic approach to pharmaceutically interesting pyrido[2,1-b][1,3]benzothiazol-1-ones via the [4+2]-cyclodimerization of acyl(1,3-benzothiazol-2-yl)ketenes generated in situ. The thermal behaviors of 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones and 3-benzoylpyrrolo[2,1-b][1,3]benzothiazole-1,2-dione (two new types of [e]-fused 1H-pyrrole-2,3-diones reported by us recently) have been studied by thermal analysis and HPLC to elucidate their capability to be a source of acyl(1,3-benzothiazol-2-yl)ketenes. As a result, we have found that only 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones are suitable for this. The experimental results are supplemented with computational studies that demonstrate that thermolysis of 3-aroylpyrrolo[2,1-c][1,4]benzothiazine-1,2,4-triones proceeds through an unprecedented cascade of two thermal decarbonylations. Based on these studies, we discovered a novel mode of thermal transformation of [e]-fused 1H-pyrrole-2,3-diones and developed a new pot, atom, and step economic synthetic approach to pyrido[2,1-b][1,3]benzothiazol-1-ones. The synthesized drug-like pyrido[2,1-b][1,3]benzothiazol-1-ones are of interest to pharmaceutics, since their close analogs show significant antiviral activity.

1H-Pyrrole-2,3-diones, fused at [e]-side with a heterocycle, are suitable platforms for the synthesis of various angular polycyclic alkaloid-like spiroheterocycles. Recently discovered sulfur-containing [e]-fused 1H-pyrrole-2,3-diones (aroylpyrrolobenzothiazinetriones) tend to exhibit unusual reactivity. Based on these peculiar representatives of [e]-fused 1H-pyrrole-2,3-diones, we have developed an approach to an unprecedented 6/5/5/5-tetracyclic alkaloid-like spiroheterocyclic system of benzo[d]pyrrolo[3′,4′:2,3]pyrrolo[2,1-b]thiazole via their reaction with Schiff bases and carbodiimides. The experimental results have been supplemented with DFT computational studies. The synthesized alkaloid-like 6/5/5/5-tetracyclic compounds have been tested for their biotechnological potential as growth stimulants in the green algae Chlorella vulgaris.

The 3-hydroxy-1,5-dihydro-2H-pyrrol-2-one motif is a valuable scaffold in drug discovery. The replacement of the 3-oxy fragment in 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones-based compounds with a 3-amino one (3-amino analogs of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, 3-amino-1,5-dihydro-2H-pyrrol-2-ones) can play a crucial role in their biological effect. Thus, approaches to 3-amino-1,5-dihydro-2H-pyrrol-2-ones are of significant interest. We developed an approach to 5-spiro-substituted 3-amino-1,5-dihydro-2H-pyrrol-2-ones that could not be obtained using previously reported approaches (reactions of 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones with amines). The developed approach is based on the thermal decomposition of 1,3-disubstituted urea derivatives of 5-spiro-substituted 3-hydroxy-1,5-dihydro-2H-pyrrol-2-ones, which were prepared via their reaction with carbodiimides.

Introduction. The state of hypoxia, causing damage and cell death, underlies many pathological processes. In addition, hypoxia induces a state of free radical oxidation, which enhances the damaging effect of hypoxic damage. This necessitates the synthesis of new compounds and the creation on their basis of drugs with antihypoxic activity.Aim. The aim of this study is the synthesis and study of the antihypoxic activity of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2Н-pyrido[4,3,2-de] quinnolin-3-ones.Materials and methods. Compounds of the 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]quinnolin-3-ones series were obtained as a result of the interaction of 2-aryl-7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids c o-tolyl-, p-tolyl-, p-fluoro-, p-nitro-, 2,4,6-trichlorophenylhydrazines. As a result, 10 substances were synthesized, the structure of which was confirmed by IR and ¹H NMR spectroscopy. The study of the antihypoxic activity of the obtained compounds was carried out using the method of normobaric hypoxia with hypercapnia («hypoxia in a jar»).Results and discussion. The studied compounds have different effects on the lifespan of mice under conditions of acute normobaric hypoxia with hypercapnia. Compounds IIIi and IIId, respectively, increased the lifespan of mice most significantly by 26.36 % and 25.64 %, respectively, compounds IIIa, IIIb, IIIg were less significant, compounds IIIc and IIIf had no effect, and compound IIIj had a prohypoxic effect.Conclusion. Compounds with the most pronounced antihypoxic and antioxidant properties have been identified. Thus, further synthesis and study of 2,5-diaryl-8,8-dimethyl-3,6,7,8-tetrahydro-2H-pyrido[4,3,2-de]cinnolin-3-ones is reasonable.