Semenishyna E. Synthesis, structure and properties of 3-alkoxy- and 3-acyloxy-1,2-dihydro-3H-1,4-benzodiazepine-2-ones

The present thesis is devoted to the synthesis, studying of physical and chemical properties and "structure - properties" relationship (pharmacological properties, affinity for benzodiazepine receptors, functional activity) of synthesized compounds. Novel 3-acyloxy-1,2-dihydro-3H-1,4-benzodiazepine-2-ones, 3-alkoxy-1,2-dihydro-3H-1,4-benzodiazepine-2-ones, 3-acyloxy-1-alkylcarbonyl-7-bromo-5-phenyl-1,2-dihydro-3H-1,4-benzodiazepine-2-ones, 3-(2-acyloxy)ethoxy-1,2-dihydro-3H-1,4-benzodiazepine-2-ones, 1-alkyl-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepine-2-ones and 1-alkyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepine-2,3-dione have been synthesized. It has been determined crystalline and molecular structure of ten synthesized compounds by the method of X-ray diffraction analysis. It has been found that mixture of 1-alkyl-3-hydroxy-1,2-dihydro-3H-1,4-benzodiazepine-2-one and 1-alkyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepine-2,3-dione was obtained as a result of the alkylation of 7-bromo-3-hydroxy-5-(2'-chloro)phenyl-1,2-dihydro-3H-1,4-benzodiazepine-2-ones with dodecyl and cetyl tosylates. In the case of alkylation with hexyl bromide or hexyl tosylate only 1-hexyl-1,2,4,5-tetrahydro-3H-1,4-benzodiazepine-2,3-diones was formed, in the case of alkylation with methyl p-toluenesulfonate or methyl benzenesulfonate only 3-hydroxy-1-methyl-1,2-dihydro-3H-1,4-benzodiazepine-2-one was obtained. Pharmaceutical properties of synthesized compounds and affinity for benzodiazepine receptors has been studied. The type of functional activity of the most affinity compounds has been determined. High analgesic activity of 3-alkoxy derivatives has been found.