Use of 2-amino-4-acetylthiazolo[5,4-b]indole hydrobromide for body protection against effect of hemic and hypercapnic hypoxia

FIELD: medicine, pharmacology, organic chemistry.

SUBSTANCE: invention relates to using 2-amino-4-acetylthiazolo[5,4-d]indole for protection of body against effect of hemic and hypercapnic hypoxia. Invention proves high effectiveness of the protection effect.

EFFECT: enhanced effectiveness of agent.

2 tbl

 

The invention relates to pharmacology and specifically relates to the new activity of the compounds of formula 1.

Previously installed hepatoprotective activity of the hydrobromide of 2-amino-4-acetylthiazole[5,4-b]indole (Patent 2076867 RF, MKI36 07 D 478/04, a 61 K 31/40. The hydrobromide of 2-amino-4-acetylthiazole[5,4-b]indole protecting the liver from carbon tetrachloride poisoning and how to obtain it /Velieva B.C., Melman A.I., Tomchin A.B., Smirnov A.V., acavity SV, Gaivoronsky V.V. (Russia). - 5042409/04; Claimed 19.05.92) and protecting high capacity at its base to the effects of hypobaric hypoxia and toxic edema (Patent 2188824 RF, MKI37 07 D 478/04, a 61 K 31/40, a 61 P 11/00. 2-Amino-4-acetylthiazole[5,4-b]indole, protect the body from the effects of hypoxia and toxic lung edema. /Marysheva CENTURIES, Shabanov P.D., Torkunov P.A., Earth AV, Vlasova MB (RF). - 2000131823/04; Claimed 18.12.2000).

A similar action is reference antihypoxic drug antizol formula 2 (Methodical recommendations for a pilot study of drugs proposed for clinical studies as antihypoxic funds. /Edited Ludlowkoeni. - M.: B. I., 1990. - 18 C.).

Himicheskaya hypoxia develops when injected into the blood of toxins, blocking g is moglobin, consequently hampered the transport of oxygen in the body and death. Poisoning of this kind is not uncommon in case of emergency chemical industries. Hypercapnic hypoxia develops in a confined space without oxygen and quickly leads to death. In case of emergency on submarines, mines, it is extremely important to prolong the life of the victim, to the rescuers managed to extract. Therefore, the search for and development of drugs that work in such situations is very important.

The purpose of this invention is a new use for compounds of a number of thiazolo[5,4-b] indole, effectively protect the body from himicheskoi and hypercapnic hypoxia and expanding Arsenal of antihypoxants.

This goal is achieved by the chemical structure of the compound 1 having the above properties. In the study of biological activity of the claimed compounds is established that protects the body from the effects of himicheskoi and hypercapnic hypoxia, which in turn suggests the possibility of using it to prevent the harmful effects of factors hypoxia and toxins.

Study of the protective effect of compound 1 in equimolar dose in relation to antipolo when exposed to hypercapnic hypoxia. Hypoxia with hypercapnia (the owner's manual on experimental (preclinical) study of new pharmacological substances. Moscow (2000), 153-158) was investigated in mice-males weighing 18-20, Animals were placed in glass jars with a volume of 250 ml with tight lids, which dipped under the water to avoid air leaks. Connection 1 in the form of a thin slurry with tween-20 was administered 30 min before hypoxia intraperitoneally. We registered the time of animal life. The activity of the claimed compounds 1 in comparison with the known analogue presented in table 1.

Table 1

Hypercapnic hypoxia
MedicationDose

mg/kg
Qty animalsLifetime minLife expectancy % compared to the controlThe increase in survival rate, %
Phys. Solution-627,97±of 5.92--
Antizol25,0744,90±8,58**160,53-
Connection 167,6642,28±4,43***151,16-
Note. The difference is significant in comparison to the control animals **R≤0,01,***p≤0,001

The effect of the drug was compared with known antihypoxic drug-antisolar in on the ze 25 mg/kg Mice in the control were treated with equivalent volumes of saline. Compound 1 significantly increases the lifetime of the animals in half, in this respect almost as good as the reference antihypoxic drug.

Gemicescuu hypoxia (Manual on experimental (preclinical) study of new pharmacological substances. Moscow (2000), 153-158) was studied on mice-males weighing 18-20, study drug in equimolarly dose in relation to antipolo was injected intraperitoneally in the form of a thin slurry with tween-20 for 30 minutes before hypoxia, which was modeled by the introduction of intraperitoneally 2% solution of sodium nitrite at a dose of 200 mg/kg the Effect of the drug was compared with known antihypoxic drug-antisolar at a dose of 25 mg/kg to Mice in the control were treated with equivalent volumes of saline. Register the lifetime of animals and the number of surviving individuals. The activity of the claimed compounds 1 in comparison with the known analogue presented in table 2.

Table 2

Himicheskaya hypoxia
MedicationDose

mg/kg
Qty animalsLifetime minLife expectancy % compared to the controlThe increase in survival rate, %
Phys. solution -729,83±to 10.09--
Antizol25,0643,07±7,21*144,38-
Connection 167,6622,71±2,4276,1366,67**
Note. The difference is significant in comparison to the control animals *-R≤0,05, **-R≤0,01

The effect of the drug was compared with known antihypoxic drug-antisolar at a dose of 25 mg/kg to Mice in the control were treated with equivalent volumes of saline.

Connection 1 on the model himicheskoi hypoxia significantly saves the life 67% of individuals, while the reference drug antizol only increases life expectancy are not keeping it.

The application of the hydrobromide of 2-amino-4-acetylthiazole [5, 4-b] indole of the formula

to protect the body from exposure to himicheskoi and hypercapnic hypoxia.



 

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