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Information × Registration Number 0224U002872, 0120U100179 , R & D reports Title Chiral neurotropic compounds, ligands of CNS receptors. Synthesis, Structure, Structure-Property Relationship popup.stage_title Head Krysko Andrii A., Кандидат хімічних наук Registration Date 07-03-2024 Organization Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine popup.description2  The purpose of the research: Establishing the pharmacological properties of the obtained compounds and screening according to the affinity of benzodiazepine receptors of the central nervous system. Synthesis of chiral 3-alkyl-3-alkoxy derivatives of 1,4-benzdiazepin-2-one. Screening studies of individual S- and R-enantiomers of 3-methyl derivatives of 7-nitro-substituted 1,4-benzdiazepines and 7-bromo-5-(2,4-dichlorophenyl)-3-methyl-1,4-benzdiazepine were carried out in mice in the "open field", corazol-induced seizure and "rotating trident" tests. (3R)-7-bromo-5-(2,4-dichlorophenyl)-3-methyl-1,4-benzdiazepine exhibits anxiolytic properties in the dose range of 4-12.7 μmol/kg. 3-(S)-7-bromo-5-(2,4-dichlorophenyl)-3-methyl-1,4-benzdiazepine at a dose of 4 μmol/kg causes an increase in the time spent by experimental animals in the central zone, which indicates the manifestation of significant anxiolytic properties of the compound. (3S)-5-(2-chlorophenyl)-3-methyl-7-nitro- and (3S)-7-bromo-5-(2,4-dichlorophenyl)-3-methyl-1,4-benzdiazepine were not detected anticonvulsant properties in antagonism tests with corazol. (3R)-3-methyl-7-nitro-5-phenyl-1,4-benzdiazepin-2-one showed moderate anticonvulsant activity. The most active were (3S)-3-methyl-7-nitro-5-phenyl-1,4-benzdiazepin-2-one and (3R)-5-(2-chlorophenyl)-3-methyl-7-nitro-1 ,4-benzdiazepin-2-one. The latter compounds showed activity greater than that of clonazepam and phenazepam. In the "rotating rod" test, the compounds mostly showed a moderate muscle relaxant effect at doses of 4-40 μmol/kg. Only (3S)-3-methyl-7-nitro-5-phenyl-1,4-benzdiazepin-2-one exhibits a pronounced myorelaxant effect; in the tested dose range, the compound causes 100% of the effect. A low level of 3-alkyl-3-alkoxy derivatives of 1,4-benzdiazepin-2-one was synthesized. The affinity of individual S- and R-enantiomers of 3-methyl derivatives of 1,4-benzdiazepin-2-one to central benzodiazepine receptors was established by radioligand analysis. Product Description popup.authors Illyushko Nataliia О. Bachinsky Serhii Yu. Burenkova Nataliia O. Holovenko Mykola Ya. Kornilov Oleksandr Yu. Krysko Andrii A. Krysko Olha L. Larionov Vitalii B. Tsapenko Zhanna М. popup.nrat_date 2024-03-07 Close