V. N. Yarovenko

Design, Synthesis and Structure-activity Studies of Rhodanine Derivatives as HIV-1 Integrase Inhibitors

Raltegravir was the first HIV-1 integrase inhibitor that gained FDA approval for use in the treatment of HIV-1 infection. Because of the emergence of IN inhibitor-resistant viral strains, there is a need to identify innovative second-generation IN inhibitors. Previously, we identified 2-thioxo-4-thiazolidinone (rhodanine)-containing compounds as IN inhibitors. Herein, we report the design, synthesis and docking studies of a series of novel rhodanine derivatives as IN inhibitors. All these compounds were further tested against human apurinic/apyrimidinic endonuclease 1 (APE1) to determine their selectivity. Two compounds showed significant cytotoxicity in a panel of human cancer cell lines. Taken together, our results show that rhodanines are a promising class of compounds for developing drugs with antiviral and anticancer properties.

Synthesis of Oxamic Acids Thiohydrazides and Carbamoyl-1,3,4-thiadiazoles

A convenient preparation method was developed for oxamic acids thiohydrazides by reaction of α-chloroacetamides with a preliminary prepared solution of elemental sulfur and hydrazines. A series of carbamoyl-1,3,4-thiadiazole derivatives was obtained.

Regioselective acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate

The influence of catalysts, acid chlorides, and solvents on the acylation of methyl 2-methyl-4H-thieno[3,2-b]pyrrole-5-carboxylate was studied. The use of AlCl3 allows the regioselective introduction of the acyl group into position 3 to be performed, whereas the acyl group is regioselectively introduced into position 6 of thienopyrrole when SnCl4 is used.

15N NMR study of the mechanism of the reaction of amidoximes with nitrites in the presence of ZnCl2 and HCl

The structures of complexes formed during the transformation of amidoximes into 1,2,4-oxadiazoles by the action of nitriles in the presence of zinc chloride and HCl were studied by15N NMR spectroscopy.

A convenient synthesis of 3-substituted 5-guanidino-1,2,4-oxadiazoles

The reaction of amidoximes with cyanoguanidine in the presence of Lewis acids affords 3-substituted 5-guanidino-1,2,4-oxadiazoles. A study of the reaction of15N-labeled chloroacetamidoxime with cyanoguanidine showed that the formation of the oxadiazole ring occursvia the elimination of the amino group from the amidoxime fragment. 1,2,4-Oxadiazoles bearing the imidazole or pyrimidine moiety were synthesized.

Synthesis and reactivity of 1-aryl-9H-thieno[3,4-b]chromon-9-ones

Methods were developed for the synthesis of 1-aryl-9H-thieno[3,4-b]chromon-9-ones based on the reaction of bromo and dibromo derivatives of 2-methyl-4H-chromon-4-one with thioacetamide in DMF. The thienochromones were modified and their fluorescence properties were studied. Bis(thienochromones) were synthesized by the reaction of thienochromones with ketoaldehydes.

A new method for the synthesis of nitriles enriched with the15N isotope

A new synthetic method for the preparation of15N-labeled nitriles from nonlabeled nitriles is proposed.

Synthesis and structure of 5-indolyl-6-thienyl-1,2,4-triazines

Acylation of indole and 2,5-dimethylthiophene with 2-(3-indolyl)-2-oxoacetyl chloride afforded the corresponding diketones. 1-(2,5-Dimethyl-3-thienyl)-2-(3-indolyl)ethanedione reacted with thiosemicarbazide under atmosperic and elevated pressure to give 6-(2,5-dimethyl-3-thienyl)-5-(3-indolyl)-2,3-dihydro-1,2,4-triazine-3-thione whose structure was studied in detail by the X-ray diffraction method. Reactions of 6-(2,5-dimethyl-3-thienyl)-5-(3-indolyl)-2,3-dihydro-1,2,4-triazine-3-thione with amines and hydrazine resulted in formation of fused triazolo- and tetrazolotriazines.

Reaction of organic nitriles with benzamidoxime

This reaction was carried out in a medium of the organic nitrile in a sealed glass ampul at 180~ for 12 h. After removal of the excess nitrile, the product was extracted with hexane and purified by thin-layer chromatography on silica gel using 2:1 benzene-hexane as the eluent. The melting point of (I) was 40-41~ [i], while the boiling point of (II) was I00I02~ (2 mm) [2]. The structures of (I) and (II) were supported by their IR and PMR spectra.

Hydrazones derived from thiooxamohydrazides and 3-formyl-4-hydroxycoumarin: synthesis, structures, and fragmentation

Novel hydrazones were obtained from thiooxamohydrazides and 3-3-formyl-4-hydroxycoumarin. According to data from NMR spectroscopy and X-ray diffraction, the coumarin fragment in the compounds obtained exists as 4-hydroxycoumarin or chromane-2,4-dione. When dissolved in dimethyl sulfoxide, these hydrazones undergo fragmentation into derivatives of 1,3,4-thiadiazole and 4-hydroxycoumarin.