RU2825134C1 - Antihyperglycemic agent - Google Patents

Abstract

FIELD: medicine; pharmaceutics.

SUBSTANCE: invention relates to use of 2-(5-oxo-2,4-diphenyl-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl-acetic acid of formula I, where R=Ph, as an antihyperglycemic agent.

EFFECT: invention provides effective hypoglycemic action.

1 cl, 2 tbl, 2 ex

Description

The invention relates to the field of organic and medicinal chemistry, namely to 2-(5-oxo-2,4-diphenyl-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl)acetic acid of formula I, where: R=Ph., which can find application in medicine as a potential antihyperglycemic agent.

The compound 2-(5-oxo-2,4-diphenyl-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl)acetic acid is known [CAS RN 2191161-19-8, entry date 03/14/2018, found in STN // REGISTRY (online)].

The biological activity and toxicity of 2-(5-oxo-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl)acetic acid are not known from patent and scientific literature.

The objective of the proposed group of inventions is to determine the possibility of using the compound as an active component of a medicinal product.

The task is accomplished by identifying the biological activity and toxicity of 2-(5-oxo-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl)acetic acid.

The proposed invention is illustrated by examples of practical implementation.

Example 1. Determination of acute toxicity of 2-(5-oxo-2,4-diphenyl-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl)acetic acid.

All animal experiments were conducted in accordance with the Decision of the Council of the Eurasian Economic Commission of November 3, 2016 N 81 "On approval of the Rules of Good Laboratory Practice of the Eurasian Economic Union in the Sphere of Circulation of Medicines" and the National Standard of the Russian Federation GOST R-53434-2009 "Principles of Good Laboratory Practice".

All experimental and control animals were taken from the same delivery and were quarantined for 14 days. Laboratory animals were kept under standard conditions of the experimental pharmacology center. All manipulations with laboratory animals were reviewed and approved at a meeting of the bioethics commission of the Federal State Budgetary Educational Institution of Higher Education St. Petersburg Chemical Federal University of the Ministry of Health of the Russian Federation.

Acute toxicity was determined on white outbred female mice weighing 22±3 g. Compound I was administered orally, once in a dose range from 500 to 1000 mg/kg as suspensions in a mixture of dimethyl sulfoxide (DMSO): water for injection (1:5). The survival of the animals was determined by observing them 24 and 48 h after the administration of the drug. The animals were observed for 72 h. The development of the main symptoms and the time of death of the animals were recorded. The experimental median lethal dose (LD50) was calculated using the installed software "STATISTICA 7.0", which uses the least squares method to calculate LD50. The median lethal dose is presented in Table 1.

According to Table 1, compound I belongs to class 3 - “moderately toxic” (according to the Hodge and Sterner classification).

Example 2. Study of the antihyperglycemic activity of 2-(5-oxo-2,4-diphenyl-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl)acetic acid.

All animal experiments were conducted in accordance with the Decision of the Council of the Eurasian Economic Commission of November 3, 2016 N 81 "On approval of the Rules of Good Laboratory Practice of the Eurasian Economic Union in the Sphere of Circulation of Medicines" and the National Standard of the Russian Federation GOST R-53434-2009 "Principles of Good Laboratory Practice".

All experimental and control animals were taken from the same delivery and were quarantined for 14 days. Laboratory animals were kept under standard conditions of the experimental pharmacology center. All manipulations with laboratory animals were reviewed and approved at a meeting of the bioethics commission of the Federal State Budgetary Educational Institution of Higher Education St. Petersburg Chemical Federal University of the Ministry of Health of the Russian Federation.

To study the antihyperglycemic effect, a model of adrenaline hyperglycemia was used. To model adrenaline hyperglycemia, white outbred female mice weighing 22±3 g were used, of which 7 groups of 5 individuals each were formed.

Hyperglycemia in animals was induced by intraperitoneal administration of a 0.01% adrenaline solution at a dose of 1 mg/kg.

Compound I was dissolved in purified water with the addition of DMSO (5:1) and administered orally through a probe in dosages of 10, 50 and 100 mg/kg. Animals of the control group received purified water in an equivalent volume. All substances were administered 30 min before pathology modeling. Blood sugar levels were recorded. The antihyperglycemic activity of the test compound was assessed by the absolute value of blood glucose concentration.

The study showed that compound I has a pronounced antihyperglycemic activity, affecting the blood glucose level caused by an injection of adrenaline.

The results of the assessment of antihyperglycemic activity are presented in Table 2.

M±SD, * - Differences with the “control after 1 hour” group are statistically significant p≤0.001.

Claims (3)

Use of 2-(5-oxo-2,4-diphenyl-5,6-dihydro-4H-1,3,4-thiadiazin-6-yl acetic acid of formula I where R=Ph, as an antihyperglycemic agent.