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Information × Registration Number 0226U001978, (0125U000750) , R & D reports Title Molecular design, synthesis and properties of target-directed derivatives of 1,4-benzodiazepines substituted in the "3" position with potential antiepileptic and related activities. popup.stage_title Молекулярний дизайн, синтез та вивчення біологічних властивостей складних ефірів 3-оксипохідних 1,4- бензодіазепіну Head Kuzmin Viktor Ye., Доктор хімічних наук Registration Date 04-02-2026 Organization Physico-Chemical Institute O. Bogatsky National Academy of Sciences of Ukraine popup.description1 Directed synthesis of new 3-substituted 1,4-benzodiazepine derivatives - highly active, effective and safe potential antiepileptic drugs. Establishment of the dependence of pharmacological properties and ligand-receptor interaction on structure. Comparative analysis and selection of compounds most promising in terms of target activity and associated properties. popup.description2 Molecular docking of a number of 1,4-benzodiazepin-2-one esters with hydrocarbon chain lengths from C1 to C7 to GABAA receptors of the human CNS was performed. According to the results of virtual screening, a pattern of change in affinity for GABAA receptors depending on the length of the hydrocarbon radical was established. The interaction of a number of 3-alkanoyloxy derivatives of 7-bromo-5-(o-chlorophenyl)-1,4-benzodiazepin-2-ones with the active center of the benzodiazepine binding site was investigated and analyzed. The pattern of change in affinity for GABAA receptors depending on the optical isomerism of 1,4-benzodiazepin-2-one esters was also established. The effect of the substituent in the p-position of the aromatic substituent on the affinity for GABAA receptors of the CNS was investigated. Based on molecular modeling, a number of promising compounds for further synthesis and further study of their affinity for GABAA receptors of the CNS were proposed. To obtain 3-acetoxy substituted 1,4-benzodiazepines, in collaboration with specialists from additional liability company "INTERCHEM", an effective method of acetoxylation of 1,4-benzodiazepines was developed, which turned out to be better than other existing methods of acetoxylation of 1,4-benzodiazepines. The proposed approach is based on the use of available sodium hypochlorite as a chlorinating agent. The use of a concentrated solution of sodium hypochlorite allows the acetoxylation process to be carried out under mild conditions and obtain target products with high yields. Under the conditions of the developed method, the synthesis of 3-hydroxy-7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one, a substance of the drug LORAZEPAM, was carried out. The synthesis consists of 4 stages: obtaining 2-amino-N-[4-chloro-2-(2-chlorobenzoyl)-phenyl]acetamide hydrochloride, obtaining 7-chloro-5-(2-chlorophenyl)-1,3-dihydro-2H-1,4-benzodiazepin-2-one. Product Description popup.authors Krysko Andrii А. Bachynskyi Serhii Yu. Illiushko Nataliia О. Zlatov Yevhen V. Viktor Y. Kuzmin Olexander Y. Kornylov popup.nrat_date 2026-02-04 Close