Tarnavsky S. Synthesis and study of antitumor activity of the derivatives of 2,5-dihydropyrrol-2,5-dione and 1,2-dihydropyrrol-3-one

Synthesis and study of antitumor activity of 2,5-dihydropyrrol-2,5-dione and 1,2-dihydropyrrol-3-one derivatives. Based on the methods of organic synthesis, biochemical testing, new 3-arylsulfanyl-, 4-arylamino-2,5-dihydropyrrol-2,5-dione was synthesized, and the structure-activity relationship was established in a number of these compounds. The results of antitumor activity in vitro showed a significant effect on the bioactivity of p-fluorobenzyl, benzyl, 2,3-dichlorophenyl and 3-chloro-4-methylphenyl substituents at position N1, m-hydroxyphenyl substituent at position C-4 and phenylsulfonyl at position C-3 of dihydropyrrole-2,5-dione. A one-step ("one-pot") preparative method for the synthesis of 3-sulfanyl derivatives of N-benzyl-4-arylamino-2,5-dihydro-1H-2,5-pyrroldione is proposed. This method has been shown to increase overall product yield and significantly reduce overall process time, compared to standard two-step synthesis. A new method for the synthesis of class 3-arylamino-2,5-dihydro-1H-2,5-pyrroldione compounds, which is formed due to the action of excess thiophenol on 3-arylsulfanyl derivatives of 4-arylamino-2,5-dihydro-1H-2,5-pyrroldione. A new class of FGFR1 protein kinase inhibitors, namely 5-amino-1-aryl-4-(1H-benzoimidazol-2-yl)-1,2-dihydropyrrol-3-ones, was identified and characterized. The new compounds of this class were synthesized and characterized by physicochemical analytical methods. It was shown that the presence of N1-unsubstituted fragment of 1H-benzoimidazole and m-hydroxyphenyl or m-chlorophenyl substituent at position 1 of 1,2-dihydropyrrol-3-one significantly increases the inhibitory activity of compounds toward FGFR1 protein kinase,.increases the inhibitory activity of the compounds. significant antitumor activity against human KG1 acute myeloid leukemia cell line and are non-toxic to conditionally normal HEK cell line293. Chemical synthesis, IR and NMR spectroscopy (1H, 13C), chromato-mass spectrometry, X-ray diffraction study, elemental analysis. Scope – bioorganic chemistry.