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
