Bachynskyi S. 3-Arylidene(hetarylidene)-1,2-dihydro-3H-1,4-benzodiazepin-2-ones. Synthesis, structure and properties

The present thesis is devoted to the synthesis of new derivatives of 3-arylidene(hetarylidene)-1,2-dihydro-3H-1,4-benzodiazepin-2-ones, studying of their physical and chemical properties, their affinity for benzodiazepine receptors (BDR) of central nervous system (CNS) and pharmacological properties. New 3-arylidene(hetarylidene)-1,2-dihydro-3H-1,4-benzodiazepin-2-ones, 3-arylidene(hetarylidene)-5-[(E)-2-aryl(hetaryl)vinyl]-1,2-dihydro-3H-1,4-benzodiazepin-2-ones. The method of synthesis of 3-arylidene(hetarylidene)-1,2-dihydro-3H-1,4-benzodiazepin-2-ones was improved to achieve yields of target compounds 60 - 90%. For the first time 3-arylidene(hetarylidene)-5-[(E)-2-aryl(hetaryl)vinyl]-1,2-dihydro-3H-1,4-benzodiazepin-2-ones were synthesized in the conditions of the developed synthetic method. Structures of five synthesized compounds were determined by X-ray analysis. It was found that the diazepine cycle has "pseudobath" conformation in crystal structure, an arylidene substituent at position 3 of the diazepine cycle has Z-configuration of the double bond and an arylvinyl substituent at position 5 has E-configuration. For the first time annelated systems on positions 1-2 of benzodiazepine cycle were synthesized based on 3-arylidene(hetarylidene)-1,2-dihydro-3H-1,4-benzodiazepin-2-ones. It was found that compounds from the series of 3-arylidene(hetarylidene)-1,2-dihydro-3H-1,4-benzodiazepin-2-ones possess high affinity for CBDR of CNS. The relationship between position and nature of substituents and affinity of compounds for CBDR and PBDR of CNS was established. Pronounced analgesic activity in the series of synthesized compounds was found and relationships between position and nature of substituents in the arylidene moiety and analgesic activity of compounds were established.