SU866966A1 - Bis(arylselenomethyl) esters exhibiting antiinflammatory and analgetic activity - Google Patents

Abstract

Bis (aripsepenometypovye) wave. The formulas AV -Se-CH2-O-CH-5b-Ar, where .Ag-.phenyl, -topyl, bevip, D-KCI lil, mesitype or p-xprenyl, exhibiting anti-inflammatory and analgesic activities.

Description

(L

with

CX)

about

Od

with

Od Isobregeyuyu refers to the new, I have described in the Pvturetura connections (aripse nometnpovym) Lg-e-CH -o-CH-Ze-Ag, () where AG - phenyl, p-topype, benzyl, p-ks / lin, mesitus or p-chorphenip, which show anti-resuscitation and anaphygetic activity and therefore are used in medicine. Compounds with antiinflammatory disorders are described in the literature (analgesic activities, for example, amidopyrine - 1-fench1-2,3-dimesh1-4-4-dimethicminoprazone-5 C1b. The aim of the invention is to expand the arsenal of means of action on a living organism. This is achieved by new compounds formulas (I) that exhibit anti-inflammatory and analgesic activities. The new compounds of formula (1) are reacted by reacting the corresponding bromomagnesium selenophenolate with dichloro ether in anhydrous diethyl ether at a The outputs of the chain of products 50-60%. The process proceeds according to the scheme 2A .. cesn20sn2se.-d -7chSёv 2 - 25bAg, where A | "- has the above significant Example 1. Synthesis of the bis- (phenylsepenometypic) ether ... To 0.1 mol of magnesium bromide from a methyl carbonate produced from 0.1 mol of bromobenzene, 0.1 magnesium atom and 0, 1 selenium atom in a medium of dry diethyl ether, 0, while cooling the reaction flask with cold water and with vigorous stirring, drop by drop. 05 mol of symmetric dichlorodimethyl ether pacivirovannogo in the double volume of anhydrous Bno- (arsh1 selenomets1) Ar Se Sech- OCHj SeAr

Divital table. Heat the reaction mixture in a water bath for 1 pg and hydrolyze with water. The organic layer is treated with 10% NaOH solution. water and dry anhydrous. All operations are conducted in an inert gas current. The solvent is distilled off, the product is distilled under vacuum. After distillation, the bis - (aryl selenomethyl) ether is closed off and further purification is carried out by recrystallization from ethyl alcohol. Yield 50%, m. 4O. Found%: 5e 44.39. S4 l40 2Calculated,%: Se 44.34. Example 2. Synthesis of bio- (mesitylsepenomethyl) ether. While cooling and stirring, 0.05 4 mol of a symmetrical dichloromethane broth dissolved in double the volume of diethyl ether was added dropwise to 0.1 mol of methyl bromide of itolium selenium. Heat the mixture for 1 h in a water bath and decompose it with water. Not dissolved in the ether bio- (mesityl selenomethyl) eff | 1p is filtered and recrystallized from ethanol. The ether layer is treated with a solution of NaOH, water, dried with anhydrous NagSO .. The ether is distilled off and another small amount of benz- (mesityl selenomethyl) ether is isolated. Yield 60%, mp. 118.5-119 ° C. Find about%: 5e 35.98. 5e. Calculated,%: 5e 35.86. The remaining compounds were obtained anapogically. Their physico-chemical contacts are presented in table. 1. Bio (aryl selenomethyl) ethers are crystalline crystalline substances that are not soluble in water, highly soluble in chloroform, benzene, diethyl acetate, and of these are poorly soluble in ether and in a tart.

2.4, in (CH) 6O 118.5-119 35.71 n-ClC H 60 79-79.5 37.39

The extinction of the new action of the new trends showed that they were suppressive in anaphygetic activity.

These compounds were tested in 6 rats of the Wistar pine and in mice (non-brewing) with intraperitoneal administration. To assess the anti-inflammatory effect, a formalin inflammation model is used, for which, under the aponeurosis of the rat's hind paw, a 2.5% solution of fi {1aline in an amount of 0.1 ml is administered. The magnitude of the edema (phenylseleno) methyl ester

Bis (mesityl)

Bis (Beveilsel & Nomethyl) Ether

Bis (p-chlorpheni71 selenomethyl) ether

Bis (2,5- "shh1bsepenometheshyuyy

Continued gab. i

 502 35.86. Se 37.15

her paws are determined by the onmetric method 3 and 6 hours after the administration of the phlogogenic agent. Test compounds are administered within 0, 5 hours and 3 hours after the administration of fori-aline.

To assess the analgesic effect, a conventional method of hot irritation is used. Amidopyrine at a dose of 100mg / kg (1/3 from Hugo) was taken as a comparison of the anti-inflammatory and ashylgetic action.

That blip 2

180

10A

5O

in

1OO

39 ± 6.5 5О t 4,1 р 0,001р О, ОО1

p 7 Oh, 5p. 0.5

69 ± 2,681 ± 5,2

4.6 41 44 t 7,9 Isspeaovanv pokaeapi that 6vo- (mezv tvpsepovometilovy) efvr protvvovospapitepnoy possesses activity, and (2,5 - ksnpsh1seavns 1W | tovy) WWF in 6vo- (p-hporfenipsepe yumetvtyuvy) 8fvr umereshyuy. Bvo-Sfenlsepevometvpovy) Werf in 6vo- (6zvspsepv (yumvtvopovy) 8fvr show a moderate anaphetchevuyu / activity.

Continued table. 2

lOO

36.4 t 4.33 The above 1a 1 soeuivn in maptoksvchl, in njlfQiOOO-3OO mg / kg. The tests are carried out in doses of 1/5 of LD5 (180,100,80,50 ig / kg). In the doses of toxic doses toxins vopenvy: gvbepv stomach EM X compounds cause. The oGpaaotA text claimed for the connection / are active and can find a name in the medication.

Claims (1)

Studies have shown that bio- (Maisy · * ce type penomeg yl) ester ₂₅ Coy possesses high anti-inflammatory activity and biological (2,5-ksilipsepenomegipov1y) ether and bis (p-hporfenipsepenometipovy) ether moderate. Bio- (fuvensepomepical) ester and bio- (benzippepenometypovy) efvr show moderate analgesic / activity. The above compounds have low toxicity, their LD ^ about 1000-300 mg / kg. The tests are carried out in doses of% 1/5 of LD ₅₀ (180,100,80,50 mg / hg). In the tested doses of toxic effects and: the death of animals does not cause a compound. Thus, the claimed compounds / are biologically active and • Chi * · -can be used in medicine.