RU-2861491-C1 - SUPRAMOLECULAR COMPLEX BASED ON 4-AMINOBUTANOIC ACID HAVING NEUROPROTECTIVE EFFECT UNDER CONDITIONS OF ISCHAEMIC BRAIN INJURY AND HYPOXIA

Abstract

FIELD: chemistry. SUBSTANCE: invention relates to a supramolecular complex based on 4-aminobutanoic acid (compound 1) having a neuroprotective effect under conditions of ischaemic brain injury and hypoxia. EFFECT: novel compound which can find use in medicine as a medicament having neuroprotective and antihypoxic activity. 1 cl, 2 ex

Inventors

• Chesalov Aleksandr Yurevich

Dates

Publication Date

20260505

Application Date

20250417

Claims (1)

1. A supramolecular complex based on 4-aminobutanoic acid, which has a neuroprotective effect under conditions of ischemic brain damage and hypoxia, compound 1

Description

Scope of application The invention relates to the field of medicine, specifically to a medicinal product possessing neuroprotective and antihypoxic activity, which is a supramolecular complex of magnesium bis-(4-aminobutanoic acid)-2-hydroxy-butanedioate, of the formula State of the art According to the WHO, the most pressing medical problem today is the prevention and treatment of cerebrovascular pathology, which causes high mortality among the population. According to the Russian Ministry of Health, as of 2023, strokes of various origins are the leading cause of death in the Russian Federation. The incidence of cerebrovascular diseases is increasing annually. High mortality rates from strokes, cerebral ischemia, and other causes, as well as disability from acute and chronic cerebrovascular accidents, are both a medical and socially significant problem. The proposed supramolecular complex is an original molecule. According to the results of patent studies of biologically active substances in Russia and abroad, Compound 1, magnesium bis-(4-aminobutanoic acid)-2-hydroxy-butanedioate, was not identified. Disclosure of invention The safety profile of a drug is crucial when developing drugs. Acute toxicity testing of Compound 1 indicates its low toxicity. Magnesium, contained in the supramolecular complex, exerts significant potential-dependent blockade of AMPA and NMDA receptors, preventing the development of glutamate excitotoxicity reactions. (Mnir K.W., Lees K.R., Ford J., 2004). 2-Hydroxybutanedioic acid, a component of Compound 1, exhibits antioxidant and membrane-stabilizing properties and inhibits lipid peroxidation processes. It activates the enzymes superoxide dismutase and catalase, improves cellular energy metabolism, and modulates the functioning of receptor complexes and the flow of ionic currents. The basis of the supramolecular complex is 4-aminobutanoic acid (GABA). The presence of GABA in brain tissue has revealed its role as a central inhibitory neurotransmitter. GABA's important role in improving cerebral blood flow and glucose utilization in the brain has also been identified. GABA's action in the central nervous system is mediated by interaction with specific GABAergic receptors. The aim of the invention is to synthesize a new compound of the supramolecular complex of magnesium bis-(4-aminobutanoic acid)-2-hydroxy-butanedioate (Compound 1) and to study its biological activity. Example 1. Synthesis of a supramolecular complex of magnesium bis-(4-aminobutanoic acid)-2-hydroxy-butanedioate (compound 1). 1) Magnesium-4-aminobutanoate was obtained by a modified method, compared to that described in the article by Kadyrova R.G., Kabirov G.F., Mullakhmetov R.R. “Development of a rational method for obtaining salts of γ-aminobutyric acid of alkali and alkaline earth metals”, Scientific Notes of the KGAVM im. N.E. Bauman. 2015. No., pp. 90-93. In a flask equipped with a stirrer and a thermometer, 5.1 g (0.05 m) of 4-aminobutanoic acid are charged, 60 ml of distilled water are poured in, the mixture is heated with stirring to 75-80 ° C, 2.0 g (0.05 m) of magnesium oxide are added, the mass is stirred for 1-1.5 hours at a temperature of 75-80 ° C, the resulting solution is filtered, and water is distilled from the filtrate in a vacuum at a temperature of 30-35 ° C. The resulting precipitate is recrystallized from propanol-2, 5.4 g (77.14%) of a white crystalline powder with T m = 198-200 ° C are obtained. 2) Obtaining a supramolecular complex of magnesium bis-(4-aminobutanoic acid)-2-hydroxy-butanedioate (compound 1). In a flask equipped with a stirrer and a thermometer, 4.42 g (0.035 m) of magnesium 4-aminobutanoate are placed, 50 ml of distilled water are poured in, the mixture is stirred and 4.7 g (0.035 m) of 2-hydroxybutanedioic acid are added, the mass is thoroughly mixed at a temperature of 35-40 °C until a solution is obtained. The solution is filtered, the water is distilled off in a vacuum at a temperature of 30-35 °C, the mass is crystallized, and dried in a vacuum at a temperature of 30-35 °C. 7.65 g (80.6%) of an almost white crystalline powder with a melting point of 169-170 °C are obtained. C 12 H 26 N 2 O 7 Mg M.m. 334.65. Found, %: C 42.91; H 7.86; N 8.31; Mg 7.17. Calculated, %: C 43.03; H 7.77; N 8.37; Mg 7.26; O 33.47. IR spectrum, ν cm -1 : 3410 (OH); 3156 (NH); 2280 (CH); 1980 (=N=); 1560 (COO - ); 1420 (CH). TLC: system - water:acetone (2:6) Rf 0.53 (one absorption zone). When performing the experimental part of the work (experiments on animals - example 2) were carried out in accordance with the requirements of GOST 33044-2014 Principles of Good Laboratory Practice: put into effect by the Order of the Federal Agency for Technical Regulation and Metrology dated October 20, 2014 No. 1700-st: date of introduction: 2015-08-01, as well as the Rules of Good Laboratory Practice of the Eurasian Economic Commission in the field of circulation of medicines: approved by the Decision of t