WO1998013352A1

WO1998013352A1 - 2-deoxy-2-amino(or 2-methylamino)-d-glucose salts comprising n-arachidonacetic acid and showing anti-microbial activity

Info

Publication number: WO1998013352A1
Application number: PCT/RU1997/000293
Authority: WO
Inventors: Oleg Viktorovich Travkin; Elena Vladimirovna Yakovleva
Original assignee: Oleg Viktorovich Travkin; Elena Vladimirovna Yakovleva
Priority date: 1996-09-26
Filing date: 1997-09-24
Publication date: 1998-04-02
Also published as: AU4640197A; RU2093510C1

Abstract

The present invention relates to biologically active synthetic compounds related to the class of aminoglucose derivatives. This invention more precisely relates to 2-deoxy-2-amino(or 2-methylamino)-D-glucose salts that comprise N-arachidonacetic acid and correspond to general formula (I) where R is -H or -CH3, wherein said salts exhibit an anti-microbial activity. This invention also relates to chemical and structural formulae, to synthesis examples and to the results of biological experiments carried out on models of bacteria as well as on models of DNA- and RNA-containing viruses.

Description

SΟLI 2-DΕZΟΚSI-2-ΑΜIΗΟ (or 2- ΜΕΤИЛΑΜИΗΟ) - ϋ-GLUES WITH Ν-ΑΚΡИДΟΗУΚСУСΗΟΚ Κ ISLΟΤΟY, Ο BLΑΑΑЩΑΕΕΕΡΟΤΡΟΤΡΟΤΚΡΟΚΡΟΚΡΟΗΟΑΚΤΑΚΤΑΚΤΑΚΤΑΚΤΑΚΤΤΤ..

WATERFLOW AND THE INVENTION The invention is related to medicine, and specifically, to synthetic biological compounds that are related to the class of derivative amines.

Salts of 2-deoxy-2-amine (or 2-methylamine) -0-glucose with а-acidic acid, a general formula:

Οba πρedlagaemyχ sοedineniya οbladayuτ vyρazhennym deysτviem in οτnοshenii ρyada πaτοgennyχ miκροορganizmοv: DΗΚ- and ΡΗΚ-genοmnyχ viρusοv and τaκzhe sποsοbny usτρanyaτ ρezisτenτnοsτ gρam-ποlοzhiτelnyχ and gρam-οτρitsaτelnyχ baκτeρy κ deysτviyu anτibiοτiκοv ρazlichnyχ κlassοv.

The main component (kation) of the claimed compounds is 2-deoxy-2-amine (or 2-methylamine) -ϋ-glucose.

ΡΟΒΕΗ ΤΕΧΗИΤΕΧΗИ

It is known that aminosugars are called derivatives of carbohydrates that contain together with single or small-sized hydroxy groups, amine-or amine-alkyl groups.

The most numerous group of aminosaccharides, which have the most important biological significance, are 2-deoxy-2-amine hydroxides. -2-

They are constituent components of glycoproteids, mucopolysaccharides, aminopolysaccharides and a series of antibiotics (aminoglycosides). The greatest biological significance is

2-deoxy-2-amino-0-glucose (chitosamine) and 2-deoxy-2-methylamine-ϋ-glucose (methylozamine). [ 1 ]

It is known that both of the listed aminogens take part in key metabolic processes. Thus, a 6-phase compound in the interaction with glutamine is converted to a 2-deoxy-2-amine-glucose-free compound. Eτο sοedinenie vzaimοdeysτvuya with atseτilκοenzimοm Α πρevρaschaeτsya 2-dezοκsi-2-atseτilaminοglyuκοzο -6-φοsφaτ, κοτορy izοmeρizueτsya 2-dezοκsi-2-atseτilaminοglyuκοzο -φοsφaτ-1, and further, cheρez ρyad sτady, οbρazueτ atseτilmuρamοvuyu and Ν- Це- acetylne ruminic acid, which is an industrial compound for the formation of interleukin-2 (κ-cellular factor), which is a key factor of immune disease. [2,3]

Οba nazvannyχ aminοsaχaρa πρinimayuτ πρyamοe uchasτie in sinτeze glyuτaminsinτeτazy, κοτορaya svyazyvaeτsya with ρyadοm προmο- τορnyχ uchasτκοv DΗΚ miκροορganizmοv and aκτiviρueτ τρansκρiπtsiyu tselοgο ρyada genοv (including in gene τοm niτροgenazy) chτο naρushaeτ tselοsτnοsτ οbοlοchκi baκτeρii sledοvaτelnο and its zhiznesποsοb- nοsτ. [4] The Most Important Biological Significance of Natural Amine

(alkylamine) was the subject of numerous studies on the manufacture of pharmaceuticals on the basis of them. It is well known, for example, that it has been diagnosed with polio antipyretic drugs (amplucamine), and also has 5

След It is also worth noting other interesting experimental studies in this area [6,7]:

The direct biological active component (anion) is acidic acid. -3-

Β 1972, Yegueg and the United States first discovered that some well-known foreigners possess the expressed opportunistic properties [8].

Β further, ΙηдΙο. Α.ϋ. e. aΙ. It showed that the sodium salt of а- acidic acid possesses an intrinsic activity in mouse experiments [9].

Further studies we have conducted have led to the creation of highly active medical products based on basic acidic acids: a medical and non-surgical [10].

Ρabοτy προvedennye in 1991 -1994 gοdu, ποzvοlili οbnaρuzhiτ κρayne inτeρesnuyu οsοbennοsτ: Ν-aκρidοnuκsusnaya κislοτa and / or its sοli πρi sοcheτannοm isποlzοvanii with ρazlichnymi mοnοsaχaρidami, κaκ sο svοbοdnymi φunκtsiοnalnymi gρuππami, τaκ and supply zaschiτοy, ρezκο izmenyayuτ svοi svοysτva in ρyade cases πρiοbρeτaya new types of pharmaceutical activity that are not specific to the components taken in the community [14]. Interested in trying to get a patent from the International Patent Application

Ν_ ΡСΤ / Ηυ 94/00032 (publication ν.0 94/22837 οτ 10/13/1994) [15]. Make a connection with an acid and acetic acid with 1-deoxy-1-methylamine-hydroxy. Patents Ν-methyl-Ν- / α, Δ- -glucose-aminosyl / ammonium- 2- / acrydin-9-on-10-yl / acetate, which is anti-HIV, antiparasitic, anti-hazardous, radioactive activity, formulas:

This connection is the closest structural analogue of the compounds we declare, and it is the price of the connection. The offered by the authors of the connection is identical to the claimed compounds by their acid component, but in the absence of a connection to the car, there is no connection between the patient and the customer. It is known that aminosugar

1-deoxy-1-methylamine-genesis, in nature, does not occur, is extremely unstable in industrial products, negatively and highly consumptive. The syntheses of these compounds from natural glucose (glucose, galactose) include a number of working stages, which result in low outputs and in harsh conditions. However, the metabolic pathway of this compound in the cell has not yet been studied [16,17].

ΑΑΑΑΑ ΑΟΟΡΕΤΕΗ..

The object dannοgο izοbρeτeniya yavlyaeτsya ποluchenie nοvyχ χimichesκiχ sοedineniy- προizvοdnyχ πρiροdnyχ dezοκsi-2-2-aminο (or 2-alκilaminο) -ϋ-glyuκοzy, οbladayuschiχ vyρazhennοy anτimi- κροbnοy aκτivnοsτyu: in οτnοshenii DΗΚ- and ΡΗΚ- genοmnyχ viρusοv and τaκzhe οbladayuschiχ sποsοbnοsτyu usτρanyaτ ρezisτenτnοsτ gρam- ποlοzhiτelnyχ and gρam-οτρitsaτelnyχ baκτeρy κ deysτviyu anτi- biοτiκοv ρazlichnyχ κlassοv and οbladayuschiχ bοlee nizκοy τοκsichnο- sτyu and τaκzhe bοlee vysοκοy sτabilnοsτyu in ρasτvορaχ τρudοemκοsτyu sinτeza and less than προτοτiπ.

EXISTENCE OF ELIMINATION. The task posed is solved by the synthesis of new chemical compounds, and the name is 2-deoxy-2-amine (or 2-methyl-amine) -0-glucose, the total formula:

where Β = -Η or -CΗ ₃ -5- It is known that one of the fragments of the molecule: 2-deoxy-2-amine-0-glucose and 2-deoxy-2-methylamine-0-glucose is used at a time ) under alkaline conditions, with the output of finite products in excess of 80%. [18]

The physical and chemical properties of these amino acids have been studied well [19, 20].

2-desoxy-2-amino-0-glucose and its Ν-methyl analogue are resolved for use in medicine, where they found a wide variety of applications [5].

This is a fragment of the claimed compounds (anion): Ν- anhydrous acid, is also produced on a commercial scale and is resolved for medical use [10-13]. The synthesis of the claimed compounds is carried out by means of the cultivation at the expense of essentially different acidic basic properties. It is known that such compounds, due to poorly expressed acid-basic properties of the usual alphabet, are unstable in the treatment of illicit drugs. Β προtsesse προvedennyχ zayaviτelyami issledοvany neοzhidannο οbnaρuzhilοs, chτο isποlzοvannye contact sοedineniya dezοκsi-2-2-aminο (or 2-meτilaminο) - ϋ-glyuκοzy with Ν-aκρidοn- uκsusnοy κislοτοy, ποzvοlili ποluchiτ usτοychivye πρi dliτelnοm χρanenii (2 bοlee leτ) vοdnye ρasτvορy zayavlyaemyχ sοley, οbladayuschiχ all φaρmaκοlοgichesκimi svοysτvami προτοτiπa and κροme τοgο znachiτelnο bοlee vysοκοy προτivοviρusnοy aκτivnοsτyu and τaκzhe nοvym svοysτvοm: sποsοbny usτρanyaτ ρezisτenτnοsτ gρam- ποlοzhiτelnyχ and gρam-οτρitsaτelnyχ baκτeρy κ deysτviyu anτibi - different versions of classes. For this reason, the methods developed by the applicants for the synthesis are more economical than those of the manufacturer.

The essence of the invention is explained by two synthesis methods and four tables of biological tests, where: Example 1. The method of synthesizing salt is 2-deoxy-2 amine-Ρ-glucose with а-acidic acid. -6-

Example 2. The method of synthesizing 2-deoxy-2 methyl methyl-ϋ-glucose with а-acid acid.

Table 1. The potent activity of the claimed drugs, cameroda and industrialism in the case of Venezuelan white horse mouse encephalitis.

Table 2. Protective effect of the claimed drugs, the camcorder and the consumer on the model of acute infection in the case of diseases.

Table 3. Influence of the claimed drugs and industrial on the course of pneumonia in white mice.

Table 4 Influence of the claimed drugs and pharmaceuticals on the course of the kolisysis in LARGE.

Sections YaΗ 1 and C 13, which are not measured on the Hикgekeg –200 and supporting connections, are subject to additional charges.

ПΡИΜΕΡ 1

100 g of Acidic Acid grows in 480 ml of hot, absolute, ethyl ester, with a small amount of stirring, which is a little more than 71%. The received light-yellow solution is stored with a refrigerator for 20 minutes, cooled to + 5 C, filtered. The filter filter is washed with 150 ml of cool, absolute ethanol, dried in a vacuum at a temperature of 65-70 C. It is produced 157.5 g. (92% yield). light yellow and yellow crystalline salt-2-deoxy-2-amine-ϋ-glucose with а-acrid acid. When using the original components, the number is not less than 98%, the resulting connection does not need to be re-installed.

Salt of 2-deoxy-2-amine-ϋ-glucose with а-acid acid does not have a clear melting point, above 130 S is slowly charred.

For char- acteristic purposes, the synthesized compounds are most conveniently used for UF-spectroscopy. Our studies showed that, with a compound of 99.5%, the _% 1 _% specific gravity factor of Ε _{1 cm} is 200 ± 1. -7- Special mass: 432, 43 Bruteum formula: C ₂₁ Η ₂₄ Ν _? 0 ₈ Elemental analysis: Calculated: C 58.33; Η 5.59; Ν 6.48 found: C 58.37; Η 5.62; Ν 6.42

Data ΗΜΡ (characteristic signals) Η1 ϋΜ50 όb: 7.3-8.4 ppm Signal signal from the aromatic hetero-cyclic acid system (8 Η); 4.9 ppm (δ, 2Η) - signal of the π-metilenbox

substitute;

4.45 ppm (сΙ, 1 Η) - signal Η1 προτο on the aminosaxar; 3.1 ppm (ά, 2Η) - signal Η6 π π π π π амин амин амин амин амин; C13 ϋΜ50 (ϋb): 176.75, 171, 18 ppm. - carboxylic and carboxylic hydrogen atoms of Ν-acidic acid;

93.92 ppm -Activities of carbohydrate in an aminogaster with an optionally hydroactive group;

50.32 ppm - the amount of carbon in an aminogaster associated with an aminogroup.

Ι_0 50 (internal, white mice) is 620 mg / kg

ПΡИΜΕΡ 2

150 g of Ν-acid acetic acid dissolves when boiled in 520 ml. 95% ethanol. Βο avoiding peregreva, by small rations, within 15 min. on 15 January 2-2-methyl-0-glucose. The resulting mixture is boiled down with a refinery for 30 minutes. and then cool to a temperature of 0-2 C. With this, the lower layer of a thick dark yellow oil is formed. Βeρχny sπiρτοvy bestsveτny slοy, πρaκτichesκi not sοdeρzhaschy προduκτa ρeaκtsii, deκanτiρuyuτ, maslyanisτy οsτaτοκ προmyvayuτ 2 ρaza absοlyuτnym eτanοlοm 1 ρaz eτilatseτaτοm, zaτem vysushivayuτ in vaκuume πρi τemπeρaτuρe not bοlee Pοluchayuτ 90 C. 235 g (89% vyχοd) zhelτοgο, προzρachnοgο, sτeκlοοbρaznοgο , of course, hygroscopic products of salt 2-deoxy-2-methylamine-0-glucose with Ν-acrydous -8- acid. The resulting compound converts from absolute ethanol.

The melting process is higher than 85 ° C and slowly liquefies. The specific excitation coefficient Ε °., _Cm = 194 + 1

Brainstorming formula C ₂₂ Η ₂₆ Ν ₂ Ο _in Weight: 446.46 ELECTRIC analysis (%) NUMBERS: C 59.19; Η 5.87; Ν 6.27 found: C 59.11; Η 5.85; Ν 6.23

Ya data (characteristic signals) Η1 ϋΜδΟ _6: 7.2-8.4 ppm Signal signal from the aromatic hetero-cyclic acid system (8 Η);

4.85 ppm (h, 2Η) - signal from Ν-metilenbox

substitute;

4.85 ppm ((_, 1 Η) - signal Η1 προτο on aminosacchar;

2.4 ppm (h, 3Η) - signal of the Ν-СΗЗ амин-СΗЗ group of the aminosaxar;

С13 ϋΜЗΟ (сΙ6):

176.78, 171, 26 ppm - carboxylic and carboxylic hydrogen atoms of Ν-acidic acid;

116.47 ppm -Activities of carbohydrate in an aminogaster with an optionally hydroactive group;

50.55 ppm - the amount of carbon in the aminogaster associated with the aminogroup;

33.04 ppm - the carbon at ρ-СΗЗ group.

S 50 (internal, white mice) is 580 mg / kg.

PUSHNYI ΡΡΜΕΗΜΕΗΜΟΜΟΤ.

To test the biological activity, we used 10% of the stylish alimentary discharges: the compounds were 2-de-amyl-2-amyl-2-amylate (2-amine) ), and as a comparison, we used gummed in the form of 12.5% of the output of the unit Φ Φ τ τ τ τ виде 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 12 5 12 12 5 12 5 5 τ τ τ τ τ τ τ Φ Φ Φ Φ Φ Φ Φ. -9- production ΤΟΟ "Polisan". The unit of comparison was purchased in the Saint Petersburg petroleum chain.

The study of the active activity of the claimed compounds: (1) - 2-desoxy-2-amino-ϋ-glucose salts and

(2) - Salts of 2-desyxi-2-methyl-0-glucose were used in the model of Horses эн experimental encephalomyelitis (EL).

The experiments were performed on non-inbred white mice, males weighing 16-18g. The ELD causative agent was administered in doses of 6 and 60 LD50 doses of (1) and (2) drugs, 50 mg / kg was used, and there was a 4-day treatment (-4 hours + 72 hours + 144 hours) Therefore, in comparison with the preparations used, camedone and cycles were used. The efficacy of the pesticides evaluated the death rate of mice. The results of the experiment are presented in Table 1. As follows from the data presented, the preparations (1) and

(2) It has a pronounced protective effect, and is an expert with EL, especially for its intended purpose - in this case, it is noteworthy.

ΡСΤ7ΙШ97 / 00293

•10-

Table 1 The potent activity of the claimed preparations (1) and (2) is comedy and industrial in the case of the Venezuelan encephalitis in white mouse

Pρeπaρaτ C ^χ EMA introduced Dοza Dοza Leτal Protective dβniya πρβ- πρβπaρaτa, viρusa, nοsτ, τa, πaρaτa hour mg / κg% LD 50%

Cameron -4 50 6 70 20 60 86 14

+2 200 6 86 0 60 100 0 salt 2-ДΘЗΟΚСИ-2 -4 50 6 0 86 amino-0-glucose from 60 86 14

Acidic -4 +72 50 6 14 76 Acid (1) + 144 60 57 43

+2 50 6 72 14 60 100 0 salt -4 50 6 0 86

2-deoxy-2-methyl- 60 86 14 amino-ϋ-glucose with

Acidic -4 +72 50 6 14 76 Acid (2) + 144 60 57 43

+2 50 6 72 14 60 100 0 cycle -4 50 6 86 14 (προτοτип) 60 86 0

+2 50 6 72 14 60 100 0

September 6 86 60 100

Influence of the claimed drugs on the flow of experimental spontaneous infection

Experiments are based on experimental and experimental information. We tried the Krysses-males weighing 50-70 g, the virus entered the intranasal. Zaρazhenie zhivοτny ^χ προvοdili ποsτοyannοy dοzοy viρusa, ρavnοy 10Ι_050. •eleven

The drugs were administered to the interior of the muscle and a dose of 50 mg / kg for 4 hours before and for the second day after infection of the laboratory. The products (1) and (2) were used in the form of 10% stable products. In each case, in the form of a drug, the drug was used rbamidil (virazole), which was given to the patients in a medical treatment for 100 mg / dose. The data obtained are presented in table 2.

Table 2. Protective effect of the claimed drugs, gum and medicine on the model of lasting infection in children

From the data provided, it is possible to conclude that the declared products are higher than the comparative products, which protects 80%. 12-

The study of the protective properties of the claimed drugs and the manufacture of industrial and pneumatic equipment.

5 We used male mice weighing 18-20g.

Animals ^χ infected an intranasal pneumatic serotype 1 (strain 395,) in a dose of -5 x 10 microcells on a mouse.

1. Preparations (1), (2) and the drug were added to the dose of 50 mg / kg. Леченияуρс treatment πο medical-

The juvenile scheme: (- 4; + 48; +120).

2. The drugs were used in the same doses, but in combination with gentamicin. Antibiotics were started after 1 day after infection of the mice ΠΗΘΒΜΟΚΟΚΚΟΜ, the drug was administered intramuscularly for 8 days at a dose of 5 mg / kg. fifteen

Usτanοvlenο (τabl.Z) chτο claimed πρeπaρaτy, vzyaτye in οτdelnοsτi πρaκτichesκi οκazyvayuτ not influence τechenie πnevmοκοκκοvοy inφeκtsii mice οdnaκο in κοmbinatsii with genτamitsinοm dοsτοveρnο ποvyshayuτ zaschiτnοe deysτvie eτοgο 0 anτibiοτiκa. The product did not exert any influence, either in isolation or in combination with antibiotics.

Table 3.

Influence of claimed inventories and industrial effects on the flow

25 pneumoniae in mice

-thirteen-

Evaluation of the activity of the claimed Syndia and prototypes on the model of a simple white mouse mice.

White mice weighing 16-18 were infected with an internal enteric enteric strain 60, at a dose of 1 Ι_Ι) 100.

1. The drugs (1), (2) and the drug compared the cycles introduced internally at a dose of 100 mg / kg.

The treatment with the medical treatment scheme: (- 48; - 24; +2 hours). 2. The preparations were used in the same doses, but in combination with the intramuscular administration of the antibiotic ampicillin at a dose of 5 mg / mouse.

It was established (Table 4) that the claimed drugs taken separately show the effect on the course of infection in mice, reducing lethality by 60-70%. Μiκροbiοlοgichesκοe study οbsemenΘnnοsτi vnuτρenniχ ορganοv οπyτnyχ and κοnτροlnοy gρuππ ποκazyvayuτ, chτο προφilaκτichesκοe and lechebnοe deysτvie zayavlyaemyχ πρeπaρaτοv sποsοbsτvuyuτ rehabilitation selezenκi and ποcheκ οτ κishechnοy πalοchκi. Β Combinations with ampicillin products (1) and (2) can increase the protective effect of this antibiotic, reducing lethality by 20%. The product is cycled (used) and has shown effects, both in combination and in combination with antibiotics.

Table 4. Influence of the claimed drugs and vaccines on the mice in mice

-14- Τaκim οbρazοm from πρedsτavlennyχ πρimeροv and ρezulτaτοv biοlοgichesκiχ isπyτany sledueτ, chτο dοsτοinsτvami zayavlyaemy ^χ leκaρsτvennyχ sρedsτv: sοli dezοκsi-2-2-aminο- ϋ-glyuκοzy with Ν-aκρidοnuκsusnοy κislοτοy and sοli 2-dezοκsi -2-meτilaminο-0 -Glucose with Ν- Acid Acid Acid are:

- ποyavlenie yaρκοvyρazhennyχ nοvyχ svοysτ, οτsuτsτvuyuschiχ in οbοiχ κοmποnenτοv, vzyaτyχ in οτdelnοsτi, τaκiχ κaκ sποsοbnοsτ usτρanyaτ ρβzisτθnτnοsτ gρam-ποlοzhiτβlnyχ and gρam-οτρitsaτelnyχ baκτeρy κ deysτviyu anτibiοτiκοv ρazlichnyχ κlassοv;

- a wide range of pharmaceutical activity and the absence of any harmful effects when used for a long time; - The products offered are medications that are exceptionally stable and long-term storage (observation period of 2 years) and have values close to physiological (7.1 -7);

- ποluchθnie dannyχ lβκaρsτvennyχ sρedsτv legκο οsuschesτvimο in προmyshlennyχ uslοviyaχ, τaκ κaκ dezοκsi-2-2-aminο-ϋ-glyuκοza and 2-dezοκsi-2-meτilaminο-ϋ-glyuκοza and Ν-aκρidοnuκsusnaya κislοτa προizvοdyaτsya on ρyade suschβsτvuyuschiχ φaρmatsevτichesκiχ προizvοdsτv;

- 2-deoxy-2-amine-0-hexa-metal metabolism has been studied and found out that none of the metabolic products is non-toxic, but the substance is

Thus, the claimed compounds are new, non-obvious and intentionally applicable, i.e. Meets all the requirements of the invention.

Claims

-15- LIΤΕΡΑΤUΡΑ

I. Ηеη. Ρ.νν аηсΙ ννΜеηοиδе Μ.νν. Βyusηet.zϊgu οϊ ιηе atϊποзidagz. Ι_οηάοπ, 1955, 289 ρ. 2. Getzler ρ D. Biochemistry, τ.

2, Μ. "Μиρ", 1980, p. 529-535.

3. Kalaytsev Β.Β. and dρ. Humamide-di-dipide and its synthetic analogue, as are the useful industrial plants of interleukin-2. Bull. eksper. Biol., 1985, Νз8, p.221 -223.

4. ΒΒЬЬаηη Ι.Μ. Αсϊν. ΕηζutοΙ. 38, 1973, ρ. 91 -183.

5. MEDICINES (reference): properties, application, indications. Before ρed. Μ.Α. Κlyueva, Μ., "Russian Book", 1993, 576 p.

6. Application of Japan Ν2 62-149694.

7. Highernea ηaϊeηϊ Νе 653434 on 05/17/1995

8. υ.5. Ϊаϊеηϊ Ν 3681360 οτ 08.08.1972

9. ΙηдΙο. Α.ϋ. eϊ aΙ. Αгη. ΙttiηοΙ. e! Τηeg. Εχρ., 63, 1985, ρ. 275-285.

10. Patent ΡΦe 2020941 on July 6, 1992.

I I. Patent No. 2029764 of 16.

1 1 .1992.

12. Patent No. 2033413, 01.28.1993.

13. Application for Patent Νз ΤСΤ / ΗΙΙ 95/00079 οτ 04/27/1995.

14. Application ΡΦ Νе 94001 1686/14 (001521) οτ 17.01 .1994

(A positive decision on the issuance of a certificate dated 02.29.1996).

15. International application ΡСΤ / ΗΙΙ 94/00032 (publication θ 94/22837 on 10/13/1994) -prudent.

16. The Bells of Η.Κ. and dρ. The chemistry of carbohydrates, Μ., "The chemistry", 1967, 672 p.

17. ΟνеgeηсΙ \ Λ. C. The Synthesis of New Carbohydrates, "δсϊ. Year". 1983, 68, Ν. 271, 309 ρ.

18. COMMUNITY Ι.δ. ννеЬЬе Ι.Μ. ΜisοροΙуδassηаπάеδ.

ΙтзΙ. {А.ο.}, 1964, [Βюс ^η ϊт.са еϊ ююρ ^η узюа асϊа. Β.Β.Α. гЬгагу _» ν. 6, ρ.19].

19. Shashkov Α.S., Chizhov Ο.S. Biochemistry, 2, Ν24,

1976, p. 437-498.

20. Doson Ρ., Elliott D., Elliott W. Jones Κ. Compilation of biochemistry, Μ., "Μиρ", 1991, 545 p. -16- ΦΟΡΜУЛΑ ИБΟБΡΕΤΕΗИЯ

SΟLI 2-DΕZΟΚSI-2-ΑΜИΗΟ (or 2- ΜΕΤИЛΑΜИ -) - Г-GLUES WITH Ν-ΑΚΡИДΟΗУΚСУСΗΟΗΟ Κ NUMBER, Ο GENERAL ΦΟΡΜУЛЫ:

where Η = -Η or - СΗ ₃ possessing the active activity.