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Information × Registration Number 0225U000186, (0120U100179) , R & D reports Title Chiral neurotropic compounds, ligands of CNS receptors. Synthesis, Structure, Structure-Property Relationship popup.stage_title Синтез білдінг-блоків для отримання цільових хіральних похідних арилпіперазинів. Молекулярний дизайн та синтез нових похідних арилпіперазинів – потенційних лігандів серотонінових рецепторів, та підтвердження структури. Скринінг отриманих сполук за афінітетом до серотонінових рецепторів та встановлення фармакологічних властивостей сполук-хітів. Head Krysko Andrii A., Кандидат хімічних наук Registration Date 07-01-2025 Organization Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine popup.description1 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. popup.description2 The purpose of the research: Molecular design and synthesis of new arylpiperazine derivatives - potential serotonin receptor ligands. Starting from Phenibut, a pair of optical isomers of 4-phenylpyrrolidin-2-one were synthesized in three stages, which were used as building blocks for obtaining ligands of serotonin receptors. For the resolution of the racemic mixture of methyl esters of 4-amino-3-phenylbutanoic acid, the method of crystallization of the corresponding diastereomeric tartrates was used. S- and R-4-Phenylpyrrolidin-2-one were used as terminal “imide” fragments for the synthesis of chiral ligands of 5-HT1A receptors. Individual optical isomers of 4-phenylpyrrolidin-2-one were alkylated with 1-(4-bromobutyl)-4-aryl-piperazine derivatives according to the method developed by us: boiling in dry toluene in the presence of potash and a catalyst – 15-crown-5. L- or D-pyroglutamic acids were also used as other terminal “amide” fragments. The latter were converted into the corresponding pentafluorophenyl esters of Boc-protected pyroglutamic acids. The assembly of the phenyl-piperazine terminal fragment began with the alkylation of di-tert-butyl-iminodicarboxylate with 1,4-dibromobutane, resulting in δ-bromo-butyl di-Boc-imide. In turn, p-nitrophenyl-piperazine was alkylated with the δ-bromo-butyl derivative obtained at the previous stage. Sequential removal of the protecting groups, condensation with activated Boc-pyroglutamic acid esters, and re-removal of Boc-protection led to chiral 5-HT1A receptor ligands. The structures of the synthesized compounds were confirmed by Mass spectrometry and NMR spectroscopy.  Product Description popup.authors Illiushko Nataliia О. Bachynskyi Serhii Yu. Burenkova Nataliia O. Нolovenko Mykola Ya. Kornilov Oleksandr Yu. Krysko Andrii А. Larionov Vitalii B. Tsapenko Zhanna М. popup.nrat_date 2025-01-07 Close