Frolov D. 3-Aryl-2-chloropropanals in the synthesis of biologically active heterocyclic compounds

The object - reagents obtained on the basis of 3-aryl-2-chloropropanals in acylation, alkylation, cyclocondensation reactions; the purpose - synthesis of amides of 5-benzyl-2-aminothiazoles, substituted pyrroles and their analogues for the research of highly active and low-toxic compounds as potential drugs with antitumor, antimicrobial and anti-inflammatory action; methods - organic synthesis, NMR spectroscopy, chromato-mass spectrometry, elemental analysis, X-ray diffraction analysis, pharmacological screening, molecular docking; results - a methodology was proposed for the liquid-phase synthesis of combinatorial libraries of 1,3-thiazole, imidazo[2,1-b]thiadiazole and pyrrole derivatives with benzyl radicals in molecules. Their structure was determined and physicochemical and spectral characteristics were studied. A study of biological activity was performed for all synthesized compounds. Antimicrobial, antitumor and anti-inflammatory effects were studied. Compounds with antitumor activity against individual lines of malignant tumors at concentrations <10nM were found. The correlation analysis "structure - antitumor action" was carried out. It is shown that the presence of a lipophilic fragment in the acid part of the amide of 5-benzyl-2-aminothiazole derivatives is a necessary condition for the anti-tumor of activity. A new way of the interrupted Feist-Benari reaction was found. The synthesis of more than 250 new heterocyclic compounds was conducted, among which 15 substances with high antitumor activity, 5 compounds with high antimicrobial action and 3 compounds with high anti-inflammatory properties with satisfactory toxicometric parameters were identified for the first time; introduced - into the educational and scientific processes of the Department of Organic Chemistry of Ivan Franko National University of Lviv; branch - pharmacy.