Search academic texts

Information × Registration Number 0221U105703, 0120U100179 , R & D reports Title Chiral neurotropic compounds, ligands of CNS receptors. Synthesis, Structure, Structure-Property Relationship popup.stage_title Head Andronati Serhii A., Доктор хімічних наук Registration Date 12-08-2021 Organization Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine popup.description2 Synthesis of building blocks to obtain target chiral derivatives of 1,4-benzdiazepine and 1,5-benzodiazocin. Molecular design, synthesis and confirmation of the structure of new chiral derivatives of 1,4-benzdiazepine and 1,5-benzodiazocin - potential ligands of benzdiazepine receptors in the CNS. A method for producing optically active 3-alkyl-substituted 1,4-benzdiazepin-2-ones is proposed, which is based on the condensation of 2-aminobenzophenones by hydrochlorides of L- or D-α-amino acids. The reaction of α-alanine hydrochloride hydrochloride with 5-nitro-2-aminobenzophenone derivatives leads to the production of 7-nitro-substituted 3-methyl-1,4-benzdiazepin-2-ones. Optimal conditions (composition and velocity of the mobile phase, column temperature) for efficient distribution of enantiomers of 3-alkyl-1,4-benzdiazepines by chiral HPLC were selected. It was found that the use of the acid chloride method leads to chiral target structures with high yields and a high degree of optical purity (more than 99%). As a result, seven pairs of optically active isomers of 3-alkyl-substituted 1,4-benzodiazepin-2-ones were synthesized. In the "open field" test, the greatest effect, which can be regarded as anxiolytic, was demonstrated by the compounds R-3-methyl-7-chloro-, S-3-methyl-7-chloro-5-(o-chlorophenyl)- and R -3-methyl-7-bromo-5- (o-fluorophenyl)-1,4-benzdiazepines. S-3-Methyl-7-chloro-5-(o-chlorophenyl)-, S- and R-3-methyl-7-bromo-5-(o-fluorophenyl)-1,4-benzodiazepines showed a significant protective effect, reaching 100 %, 66.67 % and 83.33 % respectively. Administration of test compounds at doses of 4-40 μmol/kg showed no signs of impaired coordination, loss of balance and muscle relaxation in experimental animals.  Product Description popup.authors Illyushko Natalia О. Andronati Serhii А. Bachinsky Serhii Yu. Burenkova Natalia O. Golovenko Mykola Ya. Kabanova Tetiana A. Kornylov Oleksandr Yu. Krysko Andrii А. Krysko Olga L. Larionov Vitaly Borisovich Tsapenko Zhanna М. popup.nrat_date 2021-08-12 Close