Pavlovskyy V. Derivatives of 1,4-benzodiazepine and related heterocyclic structures: synthesis, "structure-properties" relationship

Object of study: substituted 1,2-dihydro-3H-1,4-benzodiazepine-2-one and related heterocyclic compounds. Aim of reseach: molecular design and synthesis of new derivatives of dihydro-3H-1,4-benzodiazepine-2-one and related heterocyclic systems - potential ligands of central benzodiazepine receptors, establishment of communication "structure-molecular mechanisms of action-property" and evaluation of the prospects for their practical use. Methods: fine organic synthesis, 1H NMR spectroscopy, IR, UV, mass spectrometry, X-ray diffraction analysis, in vivo and in vitro pharmacology studies, radioligand analysis (affinity, internal activity). Theoretical and practical results: The methods for obtaining of 1,2-dihydro-3H-1,4-benzodiazepin-2-ones, 16- and 18-membered dioxotetrazaheterocycles have been developed. Among synthesized derivatives (3-alkoxy-, 3-acyloxy-, 3-arylamino-, 3-arylidene(hetarylidene)-1,4-benzodiazepin-2-ones) there were found about 30 compounds that have high analgesic activity. Some of these compounds with analgesic activity along with anti-inflammatory activity. An optimal method for synthesizing the substance of the drug cinazepam (levana IC) has been developed. Together with the staff of SLC "INTERCHEM", a technology for obtaining the substance was created and implemented.