Bereznyakova N. Synthesis, chemical transformation and biological properties of derivatives of 2-oxo-1,2-dihydroquinoline-3-carboxylic acids and their structural analogues

The thesis is devoted to the development of new promising research direction in the synthesis of biologically active substances as potential diuretics among the de-rivatives of 2-oxo-1,2-dihydroquinoline-3-carboxylic acids and their structural ana-logues. vA modified method for the preparation of source of ethyl ester 6-hydroxy-4-oxo-1,2-dihydro-4H-pyrrolo[3,2,1-ij]quinoline-5-carboxylic acid is proposed. On its basis the large group of amide derivatives as potentially biologically active compounds with diuretic action has been synthesized. Among the derivatives of 2-oxo-1,2-dyhidroxoquinolin-3-carboxylic acid for the first biologically active substance with diuretic action that exceed the activity of reference-drugs, and certain structural and biological regularities are obtained were discovered. For the first time 2D-QSAR-model for predicting of the biological activity of new derivatives of N-R-amides quinolincarboxylic acids is built. The chemical structure of the synthesized substances has been confirmed by elemental analysis, spectroscopy NMR, mass- and chromatomass-spectrometry, and X-ray structural analysis. The lead substance – 6-hydroxy-N-(4-metoxyphenyl)-4-oxo-1,2-dihydro-4Н-pyrrolo[3,2,1-ij]quinoline-5-carboxamide – Himopiron has been chosen, and for this substance a MCQ has been draft on which is prepared pharmacopoeial monograph of enterprise as required by GLP and temporary technological regulation in manufacture.7452