RU1828860C - 1-phenyl-4,5-bis(4-nitrobenzoyloxymethyl)-1,2,3-triazole having antiinflammatory activity - Google Patents

Abstract

The inventive product: 1-phenyl-4, 5-bis- (4-nitrobenzoyloxymethyl H, 2,3-triazole, BFS24N1708M5. Yield: 85%, mp 188-189 ° C. Reagent 1: 1 , 4-bis- (4-nitrobenzoyloxy) -butin-2, reagent 2: phenylazide, Reaction conditions1 in toluene at a boiling point of 1 table

Description

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This invention relates to the synthesis of new derivatives of 1, 2, 3-triazole, in particular to the synthesis of 1-phenyl-4, 5-bis (4-nitrobenzoyloxymethyl) -1.2, 3-triazole formLY1, -L

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possessing anti-inflammatory activity.

The aim of the invention is the synthesis of a new derivative of 1, 2. 3-triazole, which has greater activity than the known structural analogues of this action.

This goal is achieved by obtaining 1-phenyl-4, 5-bis- (4-nitrobenzoyloxymethyl) -1, 2, 3-triazole.

Example 1. The following example illustrates the method for preparing the new compound: 4.99 (0.01 g-mol) 1, 4-bis (4-nitrobenzenyloxy} -butin-2 dissolved in 20 ml dry of toluene, then 1.309 g (0.011 mol) of super-refluxed phenylazide is added. hours), the solvent is evaporated, os the residue is recrystallized in heptane. Yield 5.25 g (85%). The obtained material is odorless yellow crystals insoluble in organic solvents.

The identity was checked by TLC on AljOa 11 st. activity in the hexane ether system (5: 3). Rf-0.41 T mp 188 189 ° C

00 K) 00

IQO | about about

The structure is proven by elemental analysis. IR spectroscopy. Found. %:

C 57.29 N 3.31 N 13.98. Calculated for C24Hi7NsOe,%:

57.21 3.33 13.96

C 57.25 N 3.37 N 13.91

In the IR spectrum of the obtained compound, there are absorption bands which are characteristic of vibrations of aromatic heterocyclic rings (3200. 1550, 1450, 1270.910 cm 1).

A study on anti-inflammatory activity was carried out on white rats (weight 175-200 g) of a mixed population, the inflammation was caused by formalin, which was injected under an aponeurosis of the ankle joint with 0.2 ml of a 1% solution. Rat paw volume was measured oncometrically 3 times before and 3, 6, 24, 48, and 72 hours after formalin administration.

The test compound was administered by mouth (orally) using a metal probe in the form of an oil solution. 3-5% solution of the drug was administered at the rate of 0.1 ml per 100 g of animal body weight at doses of 25.50 and 100 mg / kg. They were administered according to a specific pattern: four times before causing inflammation: i.e., 72, 48, 24 hours and 2 hours before formalin was administered.

For comparison, the known anti-inflammatory drugs were taken - amidopyrine, butadione, indomethacin, voltaren.

As a result of the studies, it was found that the drug 1-phenyl-4, 5-bis (4-nitrobenzoyloxymethyl) -1,2,3-triazole at a dose of 25 mg / kg reduces inflammation by 37.0%, at a dose of 50 mg / kg by 59.3%, at a dose of 100 mg / kg by 39.0%. While amidopyrine at a dose of 100 mg / kg reduces inflammation by 25%, indomethacin at a dose of 100 mg / kg - 28.0%, voltaren at a dose of 25 mg / kg 39.4%, butadione at a dose of 100 mg / kg - 26.1%. These preparations were used at those doses at which, according to published data, they are most active.

The toxicity was radiated on white mice of both sexes weighing 18-23 g. The substance was administered subcutaneously as a 1-10% oil solution. The volume of the injected solution did not exceed 1 ml. The mean lethal dose (LDd) was determined by the Litchithield Wilcoxon method at P 0.04.

It is established that the described compound is low toxic. It even at a dose of 2500 mg / kg did not cause the death of animals, while amidopyrine has LDzd 225 mg / kg, butadiene LDzd 430 (344-538) mg / kg,

indomethacin LDu 47 (344-525) mg / kg, voltaren LDvo 370 (247-555) mg / kg.

From the above data it follows that 1-phenyl-4, 5-bis (4-nitrobenzoyloxymethyl) - 1, 2, 3-triazole shows a higher

anti-inflammatory activity compared with amidopyrine, butadiene, indomethacin, voltaren (basic ob-) and with structural analogues, which at a dose of 100 mg / kg (compound 2) reduces

formalin inflammation by 56% and compound 3 at a dose of 100 mg / kg reduces formalin inflammation by 59.6%,

The new compound has a higher therapeutic latitude index (50 than compound 2 (25), amidopyrine (2.25), voltaren (14.8), indomethacin (4.7), butadione (4.3, compound 3 (35) ,

Claims (1)

Claims 1-Phenyl-4,5-bis- (4-nitrobenzoyloxy methyl T.Z-triazole formula oo (О) - С-0-СН -, -, - О- СЧО) g V-T9 45 possessing anti-inflammatory activity, 51828860b Comparative characteristics of anti-inflammatory activity and toxicity of 1-phenyl-4, 5-bis (4-nitrobenzoyloxymethyl) -1, 2, 3-triazole (the claimed drug), structural analogue and well-known drugs (base object).