SU1513882A1 - Amide pentaacetylglycyrrhisin asid with octadecylamine possessing antiflammatory activity - Google Patents

Description

The invention relates to glycyrrhizic acid analogues, in particular pentaacetylglycyrrhizic acid amide, soctadecylamine, exhibiting anti-inflammatory activity. The purpose of the invention is the creation of more active and less toxic substances of the specified class. Synthesis is carried out by the reaction of pentaacetylglycyrrhizinic acid chloride with octadecylamine in tetrahydrofuran by boiling. After crystallization from a mixture of chloroform and hexane, the expected product is obtained. Output 80%, so pl. 140-143 ° C

[o /] d + 25 ° (methanol, c = 0.03), the gross formula Ογ _ο Η _<ο9 Νθ20. At a dose of 100 mg / kg, a new substance exhibits anti-inflammatory activity that exceeds the activity of the glycopeptide peptaacetylglycyrrhizic acid with 4-phenylalanine methyl ester on the formalin edema model, with toxicity = 8900 mg / kg against 1 ^) 50 =

= 8000 mg / kg. 2 tab.

1513882

The invention relates to novye chemical compounds, specifically to the amide of peitaacelglycyrrhainic,

acids with octadecylamine: 1-0- £ (3 ^) ,, 20β) -1 1, ΟΟ-ΛΗΟκοο-ΟΟ-ίΝ-οκτΒΛβπΗΠ, ΛΜΗΗο) - 18 - ^ - olean-12-en-3-yl] 2- 0β = 0-2,3,4-tri-0 - acetylglucuronopyranosyl-3,4-di-0-acetylglucurono

3

four

where K - C ^ NeUYN,

Showing ^ anti-inflammatory

activity.

The purpose of the invention is to obtain new derivatives of glycyrrhizic acid, which have advantages in pharmacological activity in comparison with known structural analogues.

1513882

The inflammation of the anti-inflammatory effect of amide I is similar to the effects of ^ lcirrieic acid, ngliein I 'is more pronounced than that of voltaren (at a dose of 50 mg / kg). In formalin inflammation, compound 1 retards the development of inflammatory edema in the same way as voltaren, nglieinu and glycyrrhizin

Example 1. Getting amide 1.10 acid (see tab.1).

To 1.3 g (1 mmol) of pentaacetylglycyrrhizinic acid trichloride in 50 ml of dry tetrahydrofuran add 1 * 1 g (4 1 mol) octadecylamyl and reflux. Cool the mixture to room temperature and drink it with a meteorological solution in ice water acidified with hydrochloric acid. The precipitate is filtered off, washed with cold water to 20 neutral and suiat. The first product is recrystallized from chloroform - hexane. Output 1.4 g "(80X), mp. 140-143 ^e C, £ ¢¢ £ + 25 °

(MeOH, c = 0.03), K £ = 0.44 (benzene alcohol 5: 1, silufol); IR spectrum ,,

cm- ': 3400 (ΝΗ), 1750 (OAc), 1660

(с ”= 0), 1540 anhydrous.).

Found X: N, 0.79.

^With YuN * _{O ()} H0

with

(SOON), 1800 (C = 0 C, 65.24; H, 8.52;

Wislönb, X: C 65.45; H 8.55;

H 1.09.

The antiinflammatory activity of amide I was studied in mice in two models of inflammation caused by the introduction of a 1X = solution of carrageenin and 3XX of formalin solution into the aponeurosis of the foot.

The test compound was given animals inside * in doses of 50 and 100 mg / kg aa 1 hour before the reproduction of inflammation and 1 and 2 hours after the administration of phytogenesis. Voltaren and prediisolone, highly active antifogging used in medical practice, and structural analogs of glycyrrhenic acid (II) and its tseyatykotiiiiat (III) and the glycopeptide pentaacetylene pycrrhizinic acid with methyl ester of Atfenkpalpala-zalic acid, were used as reference substances.

It has been established that the proposed compound has a pronounced anti-inflammatory * action in doses of 50 to 100 mg / kg in both models of inflammation. On the carrageenin model

15

25

35

The proposed compound has a more pronounced anti-inflammatory * action compared to predioneolon on the model of carganenin and formalin inflammation. The anti-inflammatory effect of compound I is similar to the effect of glycopeptide IV on the carrageenan edema model and more pronounced on the formalin edema model when administered in equal doses (P <0.0001) (see table, 2).

The acute toxicity of amide I was determined on white outbreds of both sexes after a single injection into the stomach.

It is established that amide I refers. ^ k_practically non-toxic * to substances' (S) amide I is 8900 (68461 1570) mg / kg. 1D) _5o voltaren 3® 380 mg / kg, glitsyrRyeiiovoy acid 680 mg / kg, pentanikotinata 1800 mg / kg * prednieolona 680 mg / kg, glycopeptide 8000 mg / kg.

Thus, the proposed connection has anti-inflammatory

activity similar to the activity of the structural analogue, glypopeptide pentaacetylglycyrrhizic acid with methyl Avfeiilapanin ester on the 40th model of carrageenan edema and more pronounced on the formalin edema model when administered in equal doses, and is less toxic * to the substance.

45

Claims (1)

Claim Amide pentaacetylglycyrrhizinic acid with octadecylamia common form50 mules one Loyatous anti-inflammatory activity. five 1513882 6 • Table 1. Effect of amide I on carragenine and formalin inflammation Compound Dose, mg / kg Ζ increase swelling, caused by carrageenin R ' Dose, mg / kg X increase swelling, caused by Go carr genin R X increase swelling, caused formalin ' R Amid I 50 39,313,74 <0.001,100 67.6 + 7.5 <0.02 39.6 + 4.7 <0.001 Glycirri zine acid 50 36.0 ± 3.4 <0.001 100 68.1 + 4.95 <0.002 44.3 + 3.2 <0.001 Nig lysine 50 43.8 ± 2.9 <0.001 100 66.0 ± 3.9 <0.001 42.0 + 2.9 "0.001 Voltaren eight 46.8 ± 4.76 <0.02 eight 50.5 + 3.15 * 0.001 42.0 + 1.7 <0.001 Control 66.0 + 3.57 94.1 + 4.5 70.0 + 3.9 ι table 2 ι Compound Dose, mg / kg X increase carrageenan edema > P Dose, mg / kg ί X increase 1 swelling, call! bath for- I raspberries eleven ' R Amid I 50 39.1 + 4.2 <0.001 100 39.3 + 3.9 <0.001 Ptopeptide (Iv) 50 42.5 + 2.9 <0.01 100 48.9 ± 4.9 <0.05 Prednisolone ten 54.6 + 6.3 <0.01 ten 48.9 + 3.9 <0.05 Control 67.1 + 5.9 60.5 ± 4.6 --four-