SU756810A1 - Trialkylsilyl esters of gamma-trialkylsiloxyvaleric acid possessing antiinflammating and analgetic activity - Google Patents

Description

The invention relates to new chemical compounds, to trialkylsilyl ethers of β-trialkylsiloxy-. 'valeric acid of general formula T _e CH - CH-ck _z -CH _z -COO CA _2N $ ₅₎ to $ 1 _{g of} 0- (C ₂ H ₆₎ K _r where K having antiinflammatory and analgesic activity, which may find use in medicine £ 1].

The proposed compounds relate to oxygen-containing organosilicon compounds such as silyl 15 esters of z-trialkylsiloxycarboxylic acids.

The closest structural analogue _{: the} type of organosilicon compounds is ditriethylsilyl ether of min-20 dalic acid

C ₆ H ₅ -CH-Coo ^ (C ₂ H $) s

OY1 C ^ ₂ ^ 5) of 25 that was obtained mandelic acid by reaction with triethylsilane in the presence of a catalyst tris-trifenilfosfinhlorrodiYa £ 1].

However, no data on the biological activity of these compounds are available.

The aim of the invention is to expand the arsenal of means of exposure to a living organism.

This goal is achieved by compounds of the formula 1 having anti-inflammatory and analgesic activity.

These compounds of formula T are prepared by reacting levulinic acid with trialkylsilane in the presence of colloidal nickel as a catalyst.

The preparation of trialkylsilyl esters of] -trialkylsiloxyvaleric acid occurs in two stages.

At the first stage, as a result of the interaction of levulinic acid in tetrahydrofuran with trialkylsilane, the formation of trialkylsilyl ether of levulinic acid CH3 - <2 - CH ₂ - CH ₂ - COOH + Η $ ί (CaNb) Н ^

- * Sn ₅ - S-yoyg - Sn ₂ - Soo & (S ₂ n ₅ ) I ₂ , Not about

KC _g N ₅ ; C ₄ H ₉ .

In the second stage, the purified trialkylsilyl ether of · levulinic acid reacts already without a solvent with an equimolecular amount of trialkylsilane to form the corresponding trialkylsilyl ether of .ί-trialkylsiloxyvaleric acid:

c-sn _gg ss _? & wo _(r with H5) ₂ * n k _(<r H5) of ^A

-> CH ₂ - <2N. - SL ₂ ~ CH ₂ -COOY1 (C ₂ n ₅ ) where _I οδί (s _g n ₅ ) _J2

A = r C ^ Nd,

Example. Preparation of z-Ethyldibutylsiloxyvaleric Acid Ethyldibutylsilyl Ester

A mixture of levulinic acid.

(0.1 g ”mol) dissolved in 25 ml of tetrahydrofuran and ethyl dibutylsilane (0.1 g mol) in the presence of colloidal nickel is heated at the boiling point of the reaction mixture with stirring for 6 hours. After completion of the reactions, the solvent is distilled off and the product - ethyldibutylsilyl. ester of levulinic acid is distilled in vacuum.

₉₀ T.kip. 128-130 ° C / 1mm; yield 75%

0.9341? n ^ ° 1.4455.

A mixture of freshly distilled ethyl dibutylsilyl ester of levulinic acid (0.1 g mol) and ethyl dibutyl silane (0.1 g mol) in the presence of colloidal nickel is heated for 4 hours at a temperature of 110 ° C. ' At the end of the reaction, the ethyl dibutylsilyl ester of z-ethyldibutylsiloxyvaleric acid is isolated by distillation in vacuo. Yield 90%.

The triethylsilyl ether of] -triethylsiloxyvaleric acid is obtained in a similar manner. For the final products of formula I, the following physicochemical characteristics are determined (see table. 1).

The compounds of formula I are colorless liquids with a slight odor, insoluble in water, well soluble in organic solvents.

A study of the biological effect of trialkylsilyl ethers) -trial · kylsiloxyvaleric acid showed that they have anti-inflammatory and analgesic effects.

These compounds were tested with intraperitoneal administration at a dose of 80 mg / kg (1/10 of LL _{? O} ) in white Wistar rats and white mice. To assess the analgesic effect, the hot plate technique was used. To evaluate the anti-inflammatory effect, we used a model of formalin inflammation, for which a 2.5% formalin solution in a volume of 0.1 ml was injected under the plantar aponeurosis of the hind paw. The magnitude of the edema of the foot was determined by the oncometric method of L.S. Sa45 Damon, 3 and 6 hours after the introduction of formalin. Test compounds were administered at a dose of 80 mg / kg (<£ 1/10 of LD50) for 0.5 h and 3 h after the phlogogenic agent. The control group of animals was injected with equivolume amounts of 2% starch mucus. The anti-inflammatory and analgesic effects of the claimed drugs were compared with that of amidopyrine (100 mg / kg). Studies have shown that trialkylsilyl _x esters of β-trialkylsiloxyvaleric acid have anti-inflammatory and analgesic effects. The data are given in table. 2.

The proposed drugs have low toxicity, their LD ^ -0 exceeds 800 mg / kg. They are biologically active and can find application in practical medicine.

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Claims (1)

, ' Claim Trialkylsilyl esters of] -trialkylsiloxyvaleric acid of the general formula СЛ ^ -ei-СН ^ -Снг-СООБ-! (С _а Н5-) К ₂ ο-5ΐ (ε ₂ Η _? ) Β ₂ 5 where К - С _а Н _? ; SCN ₉ , • with anti-inflammatory and analgesic activity.