A number off[4-(diethoxyphosphoryl)-2-R-1,3-oxazol-5-yl]aminogalkyl methanesulfonates were synthesized and the peculiarities of their reaction with triethylamine were studied. The influence of the structure of the 5-alkanolamine substituent on the efficiency of their transformation into 7-R-1-ethoxy-5-methyl-1,3,4,5-tetrahydro-1?(5)-[1,3]oxazolo[4,5-c][1,5,2]oxazaphosphepine-1-ones was clarified. The structure of the [1,3]oxazolo[4,5-c][1,5,2]oxazaphosphepine derivatives has been reli-ably proven by elemental analysis, IR, H-1, C-13, and P-31 NMR spectroscopy (including 1D and 2D experiments), mass spectrometry and single crystal X-ray diffraction. The oxazole cycle in [1,3]oxa-zolo[4,5-c][1,5,2]oxazaphosphepines is easily cleaved by water in an acidic environment, which leads to the formation of derivatives of the new heterocyclic system - N-(2-ethoxy-5-methyl-2-oxido-4-oxo-1,5,2-oxazaphosphepan-3-yl)arylamides.

It has been reported that the halogen dance reaction can be used to synthesize polyfunctionalized 1,3-thiazoles. The transformation into target products was carried out by lithiation of 2-bromo-5-(1,3-dioxolan-2-yl)-1,3-thiazole with lithium diisopropylamide (LDA) followed by treatment with various electrophiles. The obtained compounds were then successfully applied to prepare novel 4,5-difunctional thiazole derivatives.

This review summarizes for the first time the literature data on the methods of constructing with covalent bonds condensed systems based on 1,3-oxazoles, 1,3-thiazoles, imidazoles, phosphorus heterocycles, and their (hetero)benzo analogs. Their biological and optical properties are also considered. Methods of heterocyclization are differentiated depending on the mechanism of the reactions and the structure of the phosphorus ring. Bibliography includes 105 sources and covers the literature up to 2022.

The nitration and halogenation reactions of 2-(pentafluorosulfanyl)- and 2-(trifluoromethyl)-1,3-benzothiazoles were studied. Methods for the preparation of previously undescribed mononitro-substituted 1,3-benzothiazoles (4-nitro-2-(pentafluorosulfanyl)-1,3-benzothiazole, 4-nitro-2-(trifluoromethyl)-1,3-benzothiazole, and 6-nitro-2-(pentafluorosulfanyl)-1,3-benzothiazole) as well as a new method for the synthesis of the previously known 6-nitro-2-(trifluoromethyl)-1,3-benzothiazole were developed. The procedure involved the reaction of 2-(trifluoromethyl)-1,3-benzothiazole with NH4NO3 in TFAA at room temperature. An efficient method for the preparation of 2-substituted 4,5,6,7-tetrabromo-1,3-benzothiazoles based on the reaction of 2-substituted 1,3-benzothiazoles with NBS in TFA–H2SO4 at room temperature was proposed.

The design and development of new phosphorus-containing amino acids and peptidomimetics have been attracting considerable attention due to their value as intermediates in the synthesis of biologically active compounds and the prospects for further pharmacological applications. 1,3-Oxazole derivatives, as masked peptides, constitute an important group of amino acid precursors that are widely used in contemporary organic synthesis. This review presents the 1,3-oxazole-based synthetic strategies of phosphorylated amino acids and peptides that have been published in both journal and patent literature. We have focused specifically on the synthesis of 4-phosphorylated 1,3-oxazoles as precursors of phosphopeptide mimetics containing the peptide chain with a non-terminal phosphono group due to the growing interest in finding efficient methods for the synthesis of this little-studied class of compounds

A method for the synthesis of 5-phenyl-1,3-thiazole-4-sulfonyl chloride was developed based on the cyclization of ethyl 2-{[1-(benzylsulfanyl)-2-oxo-2-phenylethyl]amino}-2-oxoacetate obtained from available reagents under the action of the Lawesson's reagent and oxidative chlorination of the intermediate benzyl 5-phenyl-1,3thiazol-4-ylsulfide. The resulting sulfonyl chloride was converted into a series of 5-phenyl-1,3-thiazole-4-sulfonamide derivatives for which in vitro antitumor activity screening studies were performed on 60 cancer cell lines.

Anticancer activity of a series of difunctional substituted 1,2-dihydrophthalazines has been studied within the international scientific program "NCI-60 Human Tumor Cell Lines Screen". Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries, prostate, and breast cancer, epithelial cancer, leukemia, and melanoma. The most effective compounds were those with an aryl substituent at N-2 of the phthalazine cycle: 4-(4-chlorophenyl)-2-(4-methylphenyl)-1,2-dihydrophthalazine (average lg GI50 = -5.79, lg TGI = -5.42, lg LC50 = -4.97), and 2,4-bis(4-chlorophenyl)-1,2-dihydrophthalazine (average lg GI50 = -5.57, lg TGI = -5.08, lg LC50 = -4.61).

Досліджено властивості діетилових естерів 2-арил-1,3-оксазол-4-ілфосфонових кислот, що містять (2-гідроксіетил)аміногрупу в положенні 5 оксазольного циклу, корисну для подальших структурних перетворень. Ацилюванням діетил 2-арил-5-[(2-гідроксіетил)аміно]-1,3-оксазол-4-ілфосфонатів мезилхлоридом у тетрагідрофурані у присутності триетиламіну отримані 2-{[2-арил-4-(діетоксифосфорил)-1,3-оксазол-5-іл]аміно}етилметансульфонати. N-Метил заміщені метансульфонати у разі нагрівання з триетиламіном в ацетонітрилі, на відміну від стійких у вказаних умовах N-незаміщених похідних, перетворюються на продукти внутрішньомолекулярної циклізації 7-арил-1-етокси-5-метил-1,3,4,5- тетрагідро-1λ5-[1,3]оксазоло[4,5-с][1,5,2]оксазафосфепін-1-они – похідні нової гетероциклічної системи. Будову нових сполук доведено даними елементного аналізу, мас-спектрометрії, ІЧ спектрів і спектрів 1H, 13C, 31P ЯМР.

Anticancer activity of a series of 3-(hetaryl/aryl)amino substituted isoquinolin-1(2H)-ones has been studied within the international scientific program “NCI-60 Human Tumor Cell Lines Screen”. Screening was performed in vitro on 60 cell lines of lungs, kidneys, CNS, ovaries, prostate, and breast cancer, epithelial cancer, leukemia, and melanoma. The most effective compounds were those with thiazolyl or pyrazolyl substituent at 3-amino group and had no substituents at C(4) of the isoquinoline cycle. We identified a new lead compound, 3-(1,3-thiazol-2-ylamino)isoquinolin-1(2H)-one 12, which effectively prevents tumor cell growth (average lg GI50 = -5.18, lg TGI = -4.1, lg LC50 > -4.0) with good selectivity.

2-Aryl-2-(2-aryl-2-oxoethyl)-1H,2H,3H-imidazo[1,2-a]pyridin-4-ium bromides were obtained in the reaction of (2Z)-4-bromo-1,3-diphenylbut-2-en-1-one derivatives with 2-aminopyridines in benzene. The effect of the structure of the starting reagents on the results of the reactions was studied. Antitumor activity of 2-(4-chlorophenyl)-2-[2-(4-chlorophenyl)-2-oxoethyl]-1H,2H,3H-imidazo[1,2-a]pyridin-4-ium bromide was determined, which showed high antitumor potential of the test compound on 60 human cancer cell lines.

This review summarizes for the first time the literature data on the use of aliphatic and (hetero)aromatic γ-halo-α,β-unsaturated ketones in the synthesis of heterocycles containing one or several heteroatoms in the ring and their annulated analogs. Heterocyclization methods are organized depending on the reaction mechanism. Bibliography contains 122 sources and covers publications up to 2020.

A novel method for the synthesis of pyrido[1,2-b][2]benzazepine derivatives is based on the reaction of 2-(bromomethyl)benzophenones and 2-(bromomethyl)benzaldehyde with 2-methylpyridines. The route of synthesis of 6H-pyrido[1,2-b][2]benzazepinium salts includes several steps with the possibility of isolating intermediate 1-benzyl-2-methylpyridinium and 11-aryl-11-hydroxy-11,12-dihydro-6Hpyrido[1,2-b][2]benzazepinium bromides. The efficiency of dehydration of intermediate carbinols increases with the use of protic solvents, an increase in heating time, and in the presence of electron-withdrawing substituents in the benzazepine moiety. The structure of the reaction products was proved by mass spectrometry, IR and one- and two-dimensional correlation NMR spectroscopy.

We propose a new method for assembling the imidazo[2,1- b ][1,3]thiazole system, based on the reaction of (2 Z )-1,3-diaryl-4-bromobut-2-en-1-one derivatives with 2-aminothiazoles. The outcome of this reaction depends on the structure of the starting bromo ketone: when electron-withdrawing substituents are present in the structure of the ketone, a competing reaction occurs, which leads to the formation of 2,5-diarylfurans. Screening for antitumor activity has been performed in the case of 1-phenyl-2-(6-phenyl-5,6-dihydroimidazo[2,1- b ]- thiazol-6-yl)ethanone and this compound has shown moderate ability to suppress the growth of kidney cancer cells, with a weaker effect on the cell lines of prostate cancer, colon cancer, and leukemia.

Quaternization of 4-amino-4H-1,2,4-triazole with γ-bromodipnones and 5-(bromomethyl)-2,2,6,6-tetramethylhept-4-en-3-one occurred at the N-1 nitrogen atom, with the formation of quaternary salts that were cyclized in the presence of bases into [1,2,4]triazolo[1,5-a]-pyridine derivatives. Quaternary 4-amino-4H-1,2,4-triazolium salts and aromatic 1-amino-1H-[1,2,4]triazolo[1,5-a]pyridinium salts can be deaminated by treatment with nitrous acid, giving 1-substituted 1,2,4-triazoles and the respective [1,2,4]triazolo[1,5-a]pyridines.

A number of 1,4-benzoxathiine derivatives was obtained using ring contraction of seven-membered cycle of 3,4-dihydro-2H-1,5-benzoxathiepin-3-ol derivatives. This synthetic approach allowed to obtain the corresponding alkene, alcohol, nitrile, chloride, bromide, azide, and amine.

A new approach to the development of a number of azolo-condensed azepines and diazepines has been proposed. The method for the synthesis of [1,3]thiazolo[3,2-b][2,4]benzodiazepine, benzimidazo[1,2-b][2,4]benzodiazepine and benzimidazo[1,2-b][2]benzazepine derivatives involves the reaction of [2-(bromomethyl)phenyl](4-chlorophenyl)methanone with 5-methyl-1,3-thiazol-2-amine, 1H-benzimidazol-2-amine and 1,2-dimethyl-1H-benzimidazole. The formation of the quaternary salt of the initial diazole has been done under mild conditions in MeCN. The following intramolecular condensation has been realized by heating 2-amino azolium salts in AcOH or in Et3N as in the case of 2-methyl azolium salt. The structures of these cyclic compounds have been confirmed by mass spectrometry measurements, elemental analysis and NMR spectra.

The reaction result of a,b-unsaturated g-bromoketones with hydrazines depends on the structure of the reagents. Reaction with hydrazine hydrate leads to the mixture of 3,5- di(R)pyridazine, 3,6-di(R)pyridazine and 2,4-di(R)-1H-pyrrol-1-amine derivatives. The formation of three types of products is due to the structure of the unsaturated aliphatic ketone. Two competing reaction schemes of ketones with hydrazines are considered, which include condensation or Michael-type addition in the first stage. The main products of the reactions of halogen-substituted derivatives of g-bromodipnone with arylhydrazines are 1,3,5-triaryl-1,6-dihydropyridazines, which easily form aromatic salts under reaction conditions (when heated in EtOH).

The reaction result of alpha,beta-unsaturated gamma-bromoketones with hydrazines depends on the structure of the reagents. Reaction with hydrazine hydrate leads to the mixture of 3,5-di(R) pyridazine, 3,6-di(R)pyridazine and 2,4-di(R)-1H-pyrrol-1-amine derivatives. The formation of three types of products is due to the structure of the unsaturated aliphatic ketone. Two competing reaction schemes of ketones with hydrazines are considered, which include condensation or Michael-type addition in the first stage. The main products of the reactions of halogen-substituted derivatives of gamma-bromodipnone with arylhydrazines are 1,3,5-triaryl-1,6-dihydropyridazines, which easily form aromatic salts under reaction conditions (when heated in EtOH).

Piperidines spiro-fused to other heterocycles and being structural elements of pharmacologically active molecules can be considered as “preferred fragments” of metabotropic receptor ligands. The method for obtaining 1,2,8-triazaspiro [4.5]decane comprising spiroannelation of 1,4-dihydropyridine and pyrazolone cycles. When heating of 1-(phenyl)alkyl-4-[2-[2-arylhyqrazono]-1,3-dioxobutyl]pyridinium halide in pyridine or by reacting of 1-(phenyl)alkyl-4-[2-[2-arylhyqrazono]-1,3-dioxobutyl]pyridinium halides and 1-(phenyl)alkyl-4-{1,3-dioxo-3-phenyl-2-[2-(4-methylphenyl)hydrazono]propyl}pyridinium halides with diisopropylethylamine at 25°C the intramolecular reductive alkylation of the electrophilic pyridinium cation occurs forming 1-(phenyl)alkyl-3-acyl-1,2,8-triazaspiro[4.5]decanes, which are solid coloured substances. The spectral properties of the cyclization products have been studied; formation of the spiro-fused system and the presence of the 1,4-dihydropyridine fragment have been determined. Confi rmation of their structure has been obtained by carrying out the X-ray diffraction of 3-acetyl-8-benzyl-1-phenyl-1,2,8-triazaspiro[4.5]deca-2,6,9-trien-4-one crystal, which, in its turn, has clearly confi rmed orthogonality of the spiro-fused planes. The dihydropyridine ring in the molecule is not fl at and is located in the half-chair conformation with deviation of carbon spiro atom from the plane of the rest atoms of the cycle. This is due to formation of the intramolecular C-H...π hydrogen bond.