Registration Number
0224U002872,
(0120U100179)
, R & D reports
Title
Chiral neurotropic compounds, ligands of CNS receptors. Synthesis, Structure, Structure-Property Relationship
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Синтез хіральних 3-алкоксипохідних 1,4-бенздіазепіну. Вивчення афінітету похідних флавоноїду та модифікованих похідних 1,4-бенздіазепіну або 1,5-бензодіазоцину до центральних бенздіазепінових рецепторів. Встановлення фармакологічних властивостей сполук-хітів. Аналіз механізмів центральної нейроактивної дії.
Head
Krysko Andrii A., Кандидат хімічних наук
Registration Date
07-03-2024
Organization
Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine
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Synthesis of new chiral benzodiazepine and serotonin ligands of CNS receptors. Establishment of dependence of ligand-receptor interaction, pharmacological properties on the structure and configuration of the optical center.
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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
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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.
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2024-03-07
