Derivatives of neuraminic acid, or their pharmaceutically acceptable salts or their esters, as well as a pharmaceutical composition having sialidase - inhibitory activity


C07D309/28 - with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms

 

(57) Abstract:

Derivatives of neuraminic acid of the formula I, where R1- C1-C4-alkyl or C1-C4-haloalkyl; R2and R3is a hydrogen atom or a C2-C25-aliphatic acyl group; X is hydroxy, halogen, alkoxy or a group of the formula RaO-, where Ra- C2-C25-aliphatic acyl group; Y represents a group of formula RbRcN or RbRcN-O-, where Rband Rcis a hydrogen atom or a C1-C4-alkyl; Z is oxygen atom or sulfur atom; or their pharmaceutically acceptable salts possess excellent inhibitory activity against sialidase and which therefore are useful for the treatment and prevention of influenza and other viral diseases, where the replication of the virus is sensitive to inhibitors sialidase. 3 C. and 25 C.p. f-crystals, 6 PL.

This invention relates to a series of new derivatives of neuraminic acid, which have excellent inhibitory activity against sialidase and are, therefore, useful for the treatment and prevention of influenza and other viral diseases, where the replication of the virus is sensitive to inhibitors sialidase. The invention also ochotnych viral infections, as well as the methods for obtaining these compositions.

The compounds of this invention have the structure of 2-deoxy-2,3-didehydro-allairlines acid. Salimova acid is-acetylneuraminic acid.

The influenza virus, as well as several other types of the virus, has sialidase on the surface of viral particles. During replication of such viruses, the virus progeny (Balk virus) develops on the surface of infected cells and then separated from the cells. Virus progeny binds to sialic acid on the cell surface through hemagglutinin on the surface of virus progeny. Virus progeny is separated from the cells by degradation of sialic acid sialidase on the surface of virus progeny, after which it then infects other cells.

Accordingly, removal of virus progeny from the surface of infected cells can be blocked by inhibiting the activity of sialidase and, thereby, it is possible to prevent secondary infection. Therefore, I believe the substance having an ability of inhibiting the action of sialidase, can be useful for the treatment or prevention of influenza.

A series of compounds having inhibitory sialidase activity and paponi (Kokoku) N. Hei 5-507068]. Other such compounds known from WO 92/26933.

We have found a number of new compounds having the main circuit 2-deoxy-2,3-didehydro-allairlines acids, which have excellent inhibitory sialidase activity, which is significantly greater than the activity known before the present compounds referenced above and which, therefore, can be used for the treatment and prevention of influenza and other diseases caused by validatename viruses.

The invention

Accordingly, the purpose of this invention is the development of a number of new compounds that have inhibitory sialidase activity.

Other objectives and advantages of this invention become apparent from the following description.

The compounds of this invention are compounds of formula (1):

< / BR>
where R1represents an alkyl group having from 1 to 4 carbon atoms, or haloalkyl group having from 1 to 4 carbon atoms;

R2and R3are the same or different from each other, and each represents a hydrogen atom or an aliphatic acyl group having from 2 to 25 carbon ItemGroup formula RaO-, where Rarepresents an aliphatic acyl group having from 2 to 25 carbon atoms;

Y represents a group of formula RbRcN or RbRcN-O-, where Rband Rcare the same or different from each other, and each represents a hydrogen atom or alkyl group having from 1 to 4 carbon atoms;

Z represents an oxygen atom or a sulfur atom;

Provided that when Y is amino group and Z represents an oxygen atom, X represents a halogen atom or alkoxy group;

and their pharmaceutically acceptable salts and esters.

This invention also provides a pharmaceutical composition for treating or preventing infections in a mammal, which may be caused validatename viruses, such as family viruses influenza, and this composition comprises an inhibitory sialidase compound in a mixture with a pharmaceutically acceptable carrier or diluent, where the inhibitory sialidase connection represents at least one compound selected from the group consisting of compounds of the formula I and their pharmaceutically acceptable salts and esters.

In addition, this from the EC, caused validatename virus, such as a virus of the family of influenza, and this method includes the introduction of the specified mammal an effective amount inhibits sialidase connection, and inhibiting sialidase compound is at least one compound selected from the group consisting of compounds of the formula I and their pharmaceutically acceptable salts or esters.

The invention also provides methods of making compounds of the present invention, and these methods are described in detail below.

A detailed description of the invention

The compounds of this invention are called based on the terminology of saccharides, in which the main provisions are numbered as indicated in the following formula:

< / BR>
Compounds referred to as unsaturated sugar non-2 - topiramate (enopyranosoic) acid:

< / BR>
The configuration of the carbon atoms in positions 4-7 are galacto, while the configuration of the carbon atom at the 8-position is-glycero as follows from the following private formula:

< / BR>
In the compounds of this invention where R1represents an alkyl group, this group may be a group with a straight or branched chain, having the, boutelou, isobutylene, second-boutelou and t-boutelou groups, of which methyl group is preferable.

In the case where R1is haloalkyl group, the halogen atom may be a fluorine atom, chlorine, bromine or iodine, preferably fluorine atom, chlorine or bromine, and more preferably a fluorine atom. The alkyl part of this haloalkyl group can represent any of the above alkyl groups having from 1 to 4 carbon atoms. Specific examples of such haloalkyl groups include formeterol, deformational, triptorelin, 1-foretelling, 2-foretelling, 1-forproperty, 2-forproperty, 3-forproperty, 4-terbutaline, chlormethine, 1-chloraniline, 2-chloraniline, 1-chloropropylene, 2-chloropropionyl, 3-chloropropylene, bromatology, 1-bromatology, 2-bromatology, 1-bromopropyl, 2-bromopropyl and 3-bromopropyl group, of which preferred a methyl group substituted by at least one fluorine atom, especially permetrina or deformational group.

More preferably, when R1represents a methyl group or halomethyl group, especially methyl, formeterol or deformational group, more p is limfaticheskoi carboxylic acyl group (acyl group, aliphatic carboxylic acids), having from 2 to 25 carbon atoms, it can be a group with a straight or branched chain, and preferably is alkanoyloxy (alkylcarboxylic) group having from 2 to 25 carbon atoms. Specific examples of such groups include acetyl, propionyl, butyryloxy, isobutyryloxy, pivaloyloxy, valerino, isovaleryl, octanoyl, noninterpolating, metilcarbonievy, 3-methylnoradrenaline, 8-methylnoradrenaline, 3-atractylenolide, 3,7-dimethylchlorosilane, undeclinable, dodecacarbonyl, tridecylamine, tetradecylammonium, pentadecylcatechol, hexadecacarbonyl, 1-methylpentylamino, 14 - methylphenyldichlorosilane, 13,13-dimethyldichlorosilane, heptadecafluoro, 15-methylhexadecanoic, octadecylammonium, 1-methylheptadecyl, nondeclining, coolkennylee and trichotillomania group. Among them, preferred acylcarnitine group having 6 to 25 carbon atoms, more preferred acylcarnitine group having from 8 to 16 carbon atoms [and especially octonaria, monicamonica, unnecessarily (for example, dodecanoyl), t is LASS="ptx2">

R2preferably represents a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms, more preferably an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms, especially Oceanology, noninterpolating, undeclinable, tridecylamine or pentadecylcatechol group.

R3preferably represents a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms, more preferably a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms, especially Oceanology, noninterpolating, undeclinable, tridecylamine or pentadecylcatechol group.

Even more preferably, when R2represents an aliphatic acyl group having from 8 to 16 carbon atoms (especially Oceanology, noninterpolating, undeclinable, tridecylamine or pentadecylcatechol group), and R3represents a hydrogen atom.

In the case where X represents a halogen atom, it may be a fluorine atom, chlorine, bromine or iodine, preferably fluorine atom, chlorine or the t 1 to 4 carbon atoms, it can be a group with a straight or branched chain, and examples include methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy or t butoxypropyl, of which preferred methoxy, ethoxy group.

X preferably represents a fluorine atom or a methoxy or ethoxy group.

In the case where Y represents a group of the formula or, and Rband/or Rcrepresents an alkyl group having from 1 to 4 carbon atoms, it may be a group with a straight or branched chain, and examples include methyl, ethyl, sawn, ISO-propyl, boutelou, isobutylene, second-boutelou and t-boutelou groups, of which methyl group is preferable. However, most preferably, at least one and preferably both of Rband Rcwould represent a hydrogen atom. Thus, the preferred group represented by RbRcN-O-, is a group of the formula NH2-O-, and the preferred group represented by RbRcN-is the NH2-, i.e., the amino group.

Y preferably represents a group of formula NH2or NH2-O-, more preferably amino group of the formula NH2.

Z group and may therefore, to form salts with cations. There is no specific limitation on the nature of these salts, provided that when these compounds should be used in medicine, these salts must be pharmaceutically acceptable, i.e. they do not have to be any more toxic (or unacceptably more toxic) than the free acid, and should not be less active (or is less active than the free acid. When the connection is to be used for other purposes, for example as intermediates for other and perhaps more active compounds, this restriction does not apply. Examples of such salts include: salts of alkali metals such as sodium salt, potassium salt and lithium; salts of alkaline earth metals such as calcium salts and magnesium salts of other metals, such as aluminum salts, iron, zinc, copper, Nickel and cobalt; other inorganic salts such as ammonium salt; amine salts such as t-octylamine, dibenzylamine, morpholine, glucosamine, alkilany ester of phenylglycine, Ethylenediamine, methylglucamine, guanidine, diethylamine, triethylamine, dicyclohexylamine, dibenziletilendiaminom, chloroprocaine, procaine, diethanolamine, benzyl penicillin, piperazine, salts of Tetramethylammonium and Tris (who group it can also be turned into salt. Such salts are, similarly, is not particularly limited, except that in the case of medical use, they must be pharmaceutically acceptable. Examples of such salts include hydrogenogenic, such as hydroptere, hydrochloride, hydrobromide or hydroiodide; other salts of inorganic acids, such as nitrate, perchlorate, sulfate or phosphate; lower alkanesulfonyl, such as methanesulfonate, triftorbyenzola or econsultant; arylsulfonate, such as bansilalpet or p-toluensulfonate; organic acid salts, especially salts of carboxylic acids, such as acetate, triptorelin, malate, fumarate, succinate, citrate, tartrate, oxalate or maleate; and salts of amino acids such as salts of glycine, lysine, arginine, ornithine, glutamic acid or aspartic acid. Among them, preferred alkali metal salts, such as salts of sodium, potassium and lithium; salts of organic acids such as acetate and triptorelin, and inorganic salts such as hydrochloride and sulfate.

Since the compounds of this invention contain a carboxy group, they can form esters. Special restrictions on the nature of these complex efecte acceptable i.e. they should not be more toxic (or unacceptably more toxic) than the free acid, and should not be less active (or is less active than the free acid. If using this connection for other purposes, for example as intermediates for other and perhaps more active compounds, such restrictions are not required. Examples of groups that can form such esters include:

alkyl group, preferably having from 1 to 30, more preferably from 1 to 25 carbon atoms, such as methyl, ethyl, sawn, ISO-propyl, bucilina, isobutylene, second-bucilina, t-bucilina, pentilla, isopentyl, 2-methylbutyl, neopentyl, 1-ethylpropyl, hexeline, isohexyl, 4-methylpentyl, 3-methylpentyl, 2-methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutylamine, 1-methylhexane, 2-methylhexane, 3-methylhexane, 4-methylhexane, 5-methylhexane, 1-propylethylene, 4,4-dimethylpentyl, anjilina, 1-methylheptane, 2-methylheptane, 3-methylheptane, 4-methylnonane, 3-methylaniline, 4 - methylaniline, 5-methylaniline, 6-methylaniline, 1-propylhexedrine, 2-etilefrine, 6,6-dimethylheptyl, decile, 1 - methylnonane, 3-methylnonane, 8-methylnonane, 3-atrakcyjna, 3,7-dimethyloctyl, 7,7-dimethyloctyl, angellina, 4,8 - dimethylaniline, Godzilla, redecilla, tetradecyl, pentadactyla, 3,7,11-trimethyldodecane, hexadecimally, 4,8,12 - trimethylthiazole, 1-methylpentadiene, 14-methylpentadiene, 13,13-dimethyltrimethylene, heptadecyl, 15 - methylhexadecanoic, octadecyl, 1-methylheptadecyl, Donatella, Casilina, 3,7,11,15-tetramethylhexadecane, genitailia and cocosila group;

alkeneamine group, preferably having from 2 to 10, and more preferably from 2 to 8 carbon atoms, such as ethynyl, 1-propenyl, 2-propenyl, 1-methyl-2-propenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, 2-ethyl-2-propenyl, 1-butenyl, 2-butenyl, 1-methyl-2-butenyl, 1-methyl-1-butenyl, 3-methyl-2-butenyl, 1-ethyl-2-butenyl, 3-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 1-ethyl-3-butenyl, 1-pentenyl, 2-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3 - pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, the matter of from 2 to 10, and more preferably from 2 to 8 carbon atoms, such as ethinyl, 2-PROPYNYL, 1-methyl-2-PROPYNYL, 2-methyl-2-PROPYNYL, 2-ethyl-2-PROPYNYL, 2-butynyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 1-ethyl-2-butinyl, 3-butinyl, 1-methyl-3-butynyl, 2-methyl-3-butynyl, 1-ethyl-3-butinyl, 2 - pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 4-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl and 5-hexenyl group;

haloalkyl group, preferably having from 1 to 6, more preferably from 1 to 4, carbon atoms, such as triptorelin, trichlorethylene, deformational, dichlorethylene, dibromoethylene, permetrina, 2,2,2-triptoreline, 2,2,2 - trichlorethylene, 2-brometalia, 2-chloraniline, 2-florachilena, 2-iodoaniline, 3-chloropropylene, 4-terbutalina, 6-iodohexane and 2,2-dibromoethylene group;

hydroxyalkyl group, preferably having from 1 to 6, more preferably from 1 to 4, carbon atoms, such as 2-hydroxyethylene, 2,3-dihydroxypropyl, 3-hydroxiproline, 3,4-dihydroxybutyl and 4-hydroxybutyrate group;

aliphatic acetamidine alkyl groups in which the alkyl part preferably has eticeskaja acyl group, such groups as illustrated above with respect to R2and especially group having from 2 to 5 carbon atoms, such as acetylecholine group;

kalkilya group in which an alkyl group having from 1 to 6 carbon atoms, a substituted from 1 to 3, unsubstituted carbocyclic aryl groups such as benzyl, fenetylline, 3-phenylpropionate, -naphthylethylene. - naphthylethylene, diphenylmethylene, triphenylethylene, 6-phenylhexane, -afterdirectly and 9-intellilink group;

kalkilya group in which an alkyl group having from 1 to 6 carbon atoms, a substituted from 1 to 3 substituted carbocyclic aryl groups, the substituents are, for example, alkyl, alkoxy, nitro, halogen, cyano galacticosronaldo groups such as 4-methylbenzyl, 2,4,6-trimethylbenzyl, 3,4,5-trimethylbenzyl, 4-methoxybenzyl, 4-methoxy-phenyldiethanolamine, 2-nitroaniline, 4-nitroaniline, 4-chloraniline, 4-brombenzene, 4-cyano-benzyl, 4 - cyanobenzeneboronic, bis(2-nitrophenyl)methyl, piperella and 4-methoxycarbonylbenzyl group;

silyl group, including trialkylsilyl, dialkylaminoalkyl and ascidiella, triethylsilyl, isopropylideneuridine, t-butyldimethylsilyl, methyldiisopropanolamine, methyldi-t-butylstyrene, triisopropylsilyl, methyldiphenylamine, isopropylideneuridine, butyldiphenylsilyl and phenyldimethylsilane group;

alkoxyalkyl groups in which the alkoxy and alkyl parts both have from 1 to 6, preferably from 1 to 4, carbon atoms, such as methoxymethyl, 1-amoxicilina, 1-methyl-1-methoxyaniline, 1-(isopropoxy)-ethyl, 2-methoxyaniline, 2-ethoxyethylene, 1,1-dimethyl-1-methoxymethyl, ethoxymethylene, propoxymethyl, isopropoxyaniline, butoxymethyl and t-butoxymethyl group;

alkoxylalkyl groups in which each of the alkoxy units and the alkyl part, all have from 1 to 6, preferably from 1 to 4, carbon atoms, such as 2-methoxyethoxymethyl group;

aryloxyalkyl groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, such as proximately group;

halogenated alkoxyalkyl groups in which the alkoxy and alkyl parts both have from 1 to 6, preferably from 1 to 4, carbon atoms such as 2,2,2-trichloroacetimidate, both have from 1 to 6, preferably from 1 to 4, carbon atoms, such as methoxycarbonylmethyl group;

cyanoaniline groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, such cyanomethylene and 2-cyanoethylene group;

alkylthiomethyl groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, such as methylthiomethyl and ethylthiomethyl group; aristotelia groups, such as phenylthiomethyl and naphthylthiourea group;

alkylsulfonyl groups in which each alkyl parts has from 1 to 6, preferably from 1 to 4, carbon atoms, and which may be substituted by one or more halogen atoms, such as 2-methanesulfonanilide and 2-triftormetilfullerenov group;

arylsulfonyl groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, such as 2-benzolsulfonate and 2-toluensulfonyl group;

aryloxyalkyl groups, including aliphatic carboxylic aryloxyalkyl groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, and aliphatic acyl is strong, propionylthiocholine, butyrylcholine, pivaloyloxymethyl, valeriakittynice, isovalerylglycine, hexanolactone, 1-formyloxyethyl, 1-acetoxy-ethyl, 1-propionylcarnitine, 1-butyrolacetone, 1-pivaloyloxymethyl, 1-valeriakittynice, 1-isovalerylglycine, 1-hexanolactone, 2-formyloxyethyl, 2-acetoxyethyl, 2-propionylcarnitine, 2-butyrolacetone, 2-pivaloyloxymethyl, 2-valeriakittynice, 2-isovalerylglycine, 2-hexanolactone, 1-formicariidae, 1-acetoxypropionyl, 1-propionoxypiperidine, 1-butyrylcholine, 1-pivaloyloxymethyl, 1-valeriucciobello, 1-isovalerylglycine, 1-hexanoyloxyfucoxanthin, 1-acetoxymethyl, 1-propionylthiocholine, 1-butyrolactone, 1-pivaloyloxymethyl, 1-acetoxyethyl, 1-propionoxypiperidine, 1-butyrolacetone, 1-pivaloyloxymethyl and 1-pivaloyloxymethyl group;

cycloalkylcarbonyl groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, and cycloalkyl part has from 3 to 8, preferably 5 or 6, carbon atoms, such as cyclopentanecarbonitrile, 1-cyclopentanecarbonitrile, 1-cyclohexanecarbonitrile, 1-cyclopentanecarboxylate and 1-cyclohexanecarbonitrile group;

aromatic aryloxyalkyl groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, such as benzoyloxymethyl group;

(alkoxycarbonyl)alkyl groups in which the alkoxy and alkyl parts both have from 1 to 6, preferably from 1 to 4, carbon atoms, such as methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonyl, isopropoxycarbonyloxymethyl, butoxycarbonyloxyimino, msobuttoniconandcaption, pentyloxyphenylacetylene, hexyloxybenzoyl, 1-(methoxycarbonylamino)ethyl, 1-(ethoxycarbonyl)ethyl, 1-propoxycarbonyl, 1-(isopropoxycarbonyl) ethyl, 1-butoxycarbonyloxyimino, 1-msobuttoniconandcaption, 1-(tert-butoxycarbonylamino) ethyl, 1-pentyloxyphenylacetylene, 1-hexyloxyethoxy, 1-(ethoxycarbonyl) through 2-methoxycarbonylethyl, 2-ethoxycarbonylethyl, 2-propoxycarbonyl, 2-isopropoxyaniline, 2-hexyloxyethoxy, 1-methoxycarbonylpropionyl, 1-ethoxycarbonylmethylene, 1-propoxycarbonyl, 1-isopropoxycarbonyloxymethyl, 1-butoxycarbonyloxyimino, 1-msobuttoniconandcaption, 1-pentyloxyphenylacetylene, 1-hexyloxybenzoyl, 1-methoxycarbonyl-oxibutinina, 1-ethoxycarbonylmethylene, 1-propoxycarbonyl, 1-isopropoxycarbonyloxymethyl, 1-butoxycarbonyloxyimino, 1 isobutoxy-carbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-methoxycarbonylmethylene and 1-ethoxycarbonylmethylene group;

(cycloalkylcarbonyl) alkyl and (cycloalkylcarbonyl) (cycloalkyl) alkyl group in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, and cycloalkyl part has from 3 to 8, preferably 5 or 6, carbon atoms, such as cyclohexyloxycarbonyloxy, cyclohexyloxycarbonyloxy (cyclohexyl) methyl, 1-cyclopentanecarbonitrile, 1-cyclopentanecarbonitrile, 1-cyclohexyloxycarbonyloxy, 1-cyclopentanetetracarboxylic group, in which the alkyl part has from 1 to b, preferably from 1 to 4, carbon atoms, including exodeoxyribonuclease groups such as (5-phenyl-2-oxo-1,3-dioxolan-4-yl)methyl, [5-(4-were)-2-oxo-1,3-dioxolan-4-yl] methyl, [5-(4-methoxyphenyl)-2-oxo-1,3-dioxolan-4-yl] methyl, [5-(4-forfinal) -2-oxo-1,3-dioxolan-4-yl] methyl, [5-(4-chlorophenyl) -2-oxo-1,3-dioxolan-4-yl]methyl, (2-oxo-1,3-dioxolan-4-yl) methyl, (5-methyl-2-oxo-1,3-dioxolan-4-yl)methyl, (5-ethyl-2 - oxo-1,3-dioxolan-4-yl)methyl, (5-propyl-2-oxo-1,3-dioxolan-4-yl)methyl, (5-isopropyl-2-oxo-1,3-dioxolan-4-yl)methyl and (5-butyl-2-oxo-1,3-dioxolan-4-yl)methyl group;

felicilda and substituted felicilda groups, such as felicilda, dimethylpyridine and dimethoxytrityl group;

aryl group, preferably having from 6 to 14 carbon atoms in one or more carbocyclic rings, such as phenyl and indayla group;

carboxialkilnuyu groups in which the alkyl part has from 1 to 6, preferably from 1 to 4, carbon atoms, such as carboxy methyl group; and

amide-forming amino acid residues.

Of the above ester groups, the following split is s or salts by hydrolysis or similar reactions in the human body, in particular:

alkyl group, alkoxyalkyl group, alkoxylalkyl group, aryloxyalkyl group, halogenated alkoxyalkyl group, alkoxycarbonyl group, cyanoaniline group, alkylthiomethyl group, alkylsulfonyl group, arylsulfonyl group, aryloxyalkyl group (alkoxycarbonyl)alkyl groups, (cycloalkylcarbonyl)alkyl groups, (cycloalkylcarbonyl) (cycloalkyl)alkyl groups, carbonylcyanide group, phthalidyl and substituted phthalidyl group, aryl group, carboxialkilnuyu group, and amide-forming amino acid residues.

Of them, preferable are straight and branched alkyl groups having from 6 to 25 carbon atoms, more preferred alkyl group having from 16 to 25 carbon atoms.

The compound of the present invention, when it is kept in atmospheric conditions, can absorb some moisture, and it may, as a result, contact with the adsorbed water or it can turn into a hydrate. Such hydrates are also part of this invention.

Preferred classes of compounds given is:

(A) R1represents methyl or halomethyl group.

(B) R2represents a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms .

(C) R3represents a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms .

(D) X represents a halogen atom or alkoxy group having from 1 to 4 carbon atoms.

(E) Y represents an amino group or a group of the formula RbRcN-O-, where Rband Rcare as defined above.

Of the above compounds are preferred those compounds of formula I and their pharmaceutically acceptable salts and esters in which R1such as defined in (A) above, R2such as defined in (B) above, R3such as defined in (C) above, X is as defined in (D) above, and Y as defined in (E) above, particularly compounds in which R1such as defined in (A) above, R2such as defined in (B) above, R3such as defined in (C) above, X is as defined in (D) above, Y is as defined in (E) above, and Z represents an oxygen atom.

More preferred classes with the author esters, where:

(F) R1represents a methyl group or a methyl group having at least one fluorine-Deputy.

(G) R2represents a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms.

(N) R3represents a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms.

(I) X represents a fluorine atom, methoxy group or ethoxy group.

(J) Y represents an amino group or aminooxy group.

(K), Z represents an oxygen atom.

Of the above compounds are preferred those compounds of formula (I) and their pharmaceutically acceptable salts and esters where R1such as defined in (F) above, R2such as defined in (G) above, R3such as defined in (H) above, X is as defined in (I) above, Y is as defined in (J) above, and Z as defined in (K) above.

Even more preferred class of compounds of this invention are the compounds of formula (I) and their pharmaceutically acceptable salts and esters, where:

(L) R2represents a hydrogen atom or an aliphatic carboxylic acyl group, keywordpattern the compounds of formula (I) and their pharmaceutically acceptable salts and esters, where R1such as defined in (F) above, R2and R3such as defined in (L) above, X is as defined in (I) above, Y is as defined in (J) above, and Z as defined in (K) above.

Other preferred classes of compounds of this invention are the compounds of formula (I) and their pharmaceutically acceptable salts and esters, where:

(M) R1represents methyl, formeterol or deformational group.

(N) R2is octanoyl, technology, dodecanoyl, meritorious or Palmitoyl group.

(O) R3represents a hydrogen atom or octanoyl, technology, dodecanoyl, meritorious or Palmitoyl group.

(R) Y represents an amino group.

Of the above compounds are preferred those compounds of formula (I) and their pharmaceutically acceptable salts and esters where R1such as defined in (M) above, R2such as defined in (N) above, R3such as defined in (O) above, X is as defined in (I) above, Y is as defined in (B) above, and Z as defined in (K) above.

As a more preferred class of compounds of this ISOR>1represents a methyl group.

(R) R2is octanoyl, technology, dodecanoyl, meritorious or Palmitoyl group, and R3represents a hydrogen atom.

Of the above compounds, preferred compounds of formula (I) and their pharmaceutically acceptable salts and esters where R1such as defined in (Q) above, R2and R3such as defined in (R) above, X is as defined in (I) above, Y is as defined in (B) above, and Z as defined in (K) above.

Specific compounds of this invention are illustrated below with the help of formula (I'), where the group substituents are as defined in the following Tables 1 and 2. Any individual connection can be determined by taking the combination of the definitions of R1X, Y and Z in any row of Table 1 and combining them with a combination of the definitions of R2, R3and W in any row of Table 2. Then, the connection may be identified by number as is, where is the number of the corresponding row of the Table 1 and the number of the corresponding row of the Table 2. Thus, for example, the compound of formula (I) given below, which is a compound of formula (I'), where R1you submitted the ablity 1), R2represents a hydrogen atom, R3represents a hydrogen atom and W represents undecyloxy group (row 4 of Table 2) is the Compound N 1 - 4.

< / BR>
The Tables use the following abbreviations:

Bu - butyl

iBu is isobutyl

Et - ethyl

Me - methyl

Pr - propyl

iPr is isopropyl

Thus, disclosed the following connections N 1-1, 1-2, 1-3 (see end of description)

Among the combinations shown in Table 1 above, preferred are combinations of groups identified N 1, 2, 3, 4, 5, 6, 7, 8, 9, 31, 34, 35, 36, 76, 77, 78, 106, 107, 108, 136, 137, 138, 163 and 199, and more preferred combinations of the groups identified N 1, 163, 199.

Among the combinations shown in Table 2 above, preferred are combinations of groups identified N 1 - 8, 32 - 53 and 87 - 97, and more preferred combinations of the groups identified N 1, 38, 40, 41 and 42.

Among the compounds represented by combinations of the groups selected from Table 1 and table 2, the preferred are compounds N 1 - 1, 1 - 2, 1 - 3, 1 - 4, 1 - 5, 1 - 6, 1 - 7, 1 - 8, 1 - 32, 1 - 33, 1 - 34, 1 - 35, 1 - 36, 1 - 37, 1 - 38, 1 - 39, 1 - 40, 1 - 41, 1 - 42, 1 - 43, 1 - 44, 1 - 45, 1 - 48, 1 - 49, 1 - 50, 1 - 51, 1 - 52, 1 - 53, 7 - 1, 7 - 2, 7 - 3, 7 - 4, 7 - 5, 7 - 6, 7 - 7, 7 - 8, 7 - 32, 7 - 33, 7 - 34, 7 - 35, 7 - 36, 7 - 37, 7 - 38, 7 - 39, 7 - 40199 - 42.

The most preferred compounds are compounds of the following numbers:

1 - 1. 5-acetamido-4-guanidino-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-enternotify acid;

IUPAC name: 5-acetamido-6-(1-fluorescent-2,3-dihydroxypropyl)-4-guanidino-2 3 dihydropyran-2-carboxylic acid;

1 - 40. 5-acetamido-4-guanidino-9 dodecanoyl-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-enternotify acid; IUPAC name: 5-acetamido-6-(1-fluorescent-2-hydroxy-3-dodecenylsuccinic)-4 guanidino-2 3 - dihydropyran-2-carboxylic acid;

1 - 41. 5-acetamido-4-guanidino-9 myristoyl-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-enternotify acid; IUPAC name: 5-acetamido-6-(1-fluorescent-2 - hydroxy-3-myristoylation)-4 guanidino-2 3 - dihydropyran-2-carboxylic acid;

1 - 42. 5-acetamido-4-guanidino-9 Palmitoyl-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2 - enternotify acid; IUPAC name: 5-acetamido-6-(1 - fluorescent-2-hydroxy-3-palmitoylation)-4 guanidino-2- -dihydropyran-2-carboxylic acid;

163 - 1. 5-acetamido-4-guanidino-2,3,4,5,7 - pentadecane-7-methoxy glycero galacto-non-2-enternotify acid; IUPAC name: 5-acetamido-6-(2,3-dihydroxy-1-methoxypropyl)-4 guanidino-2 dayzero galacto-non-2-enternotify acid: 5-acetamido-6-(2-hydroxy-1-methoxy-3-myristoylation)-4 guanidino-2 dihydropyran-2-carboxylic acid;

199 - 1. 5-acetamido-4-guanidino-2,3,4,5, 7 pentadecane-7 - ethoxy glycero galacto-non-2-enternotify acid; IUPAC name: 5-acetamido-6-(1-ethoxy-2,3-dihydroxypropyl)-4 guanidino-2 dihydropyran-2-carboxylic acid;

199 - 38. 5-acetamido-4-guanidino-9 octanoyl-2,3,4,5,7-pentadecane-7-ethoxy glycero galacto-non-2-enternotify acid; IUPAC name: 5-acetamido-6-(1-ethoxy-2-hydroxy-3-Oceanological)-4 guanidino-2 3 dihydropyran-2-carboxylic acid;

199 - 40. 5-acetamido-4-guanidino-9 dodecanoyl-2,3,4,5,7 - pentadecane-7-ethoxy glycero galacto-non-2 - enternotify acid; IUPAC name: 5 - acetamido-6-(1-ethoxy-2-hydroxy-3-dodecenylsuccinic)-4 guanidino-2 dihydropyran-2-carboxylic acid;

199 - 41. 5-acetamido-4-guanidino-9 myristoyl-2,3,4,5,7 - pentadecane-7-ethoxy glycero galacto-non-2-enternotify acid; IUPAC name: 5-acetamido-6-(1-ethoxy-2-hydroxy-3-myristoylation)-4 guanidino-2 dihydropyran-2-carboxylic acid;

199 - 42. 5-acetamido-4-guanidino-9 Palmitoyl-2,3,4,5,7 - pentadecane-7-ethoxy glycero galacto-non-2 - enternotify acid; IUPAC name: 5-acetamido-6-(1-ethoxy-2 - hydroxy-3-palmitoylation)-4 guanidino-2 dihydropyran-2-carboxylic acid.

The compounds of this invention mailstream in the following Ways D, E, F or G.

The compound of the formula (5), which is used as the starting material in Method C can be obtained using the following Method N.

< / BR>
In the above formulas:

R1, R2, R3X and Z are such as defined above;

R2arepresents any of the groups or atoms represented by R2or hydroxyamides group, preferably t-butyldimethylsilyloxy group;

R3arepresents any of the groups or atoms represented by R3or hydroxyamides group, preferably t-butyldimethylsilyloxy group;

Xarepresents any of the groups or atoms represented by X, or protected by a hydroxy-group, preferably t-butyldimethylsilyloxy group;

W represents a hydrogen atom or difficult-volatile residue;

Warepresents any of the groups or atoms represented by W, or a carboxy-protecting group, preferably allyl group, methoxymethyl group, methylthiomethyl group, [2-(trimethylsilyl)ethoxy]methoxy group or diphenylmethylene group, more preferably diphenylmethylene group; and

Boc represents t-butoxycarbonyl group.

In this Way joint is of the compounds of formula (3), which then removes the protection.

STAGE A1

In this stage, the compound of formula (3) is produced by interaction of the compounds of formula (2) with di-t-butoxycarbonylamino in the presence of a base and mercury chloride in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. Special restrictions on the nature of the subject using the solvent does not exist, provided that it has no adverse effect on the reaction or involved in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dietilen glycol dimethyl ether; and amides, such as dimethylacetamide and dimethylformamide. Among them, preferred amides, especially dimethylacetamide or dimethylformamide.

Special restrictions on the nature of the used grounds also does not exist, and can be used equally any base commonly used in reactions of this type. Examples of such bases include: body is the eye of the temperature range, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents, bases and solvents. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 1 hour to 24 hours, more preferably from 5 hours to 10 hours.

After completion of the reaction, the desired compound can be obtained in the usual way. For example, one suitable method for detecting comprises: filtering the reaction solution under reduced pressure to remove insoluble substances; adding immiscible with water, an organic solvent, such as ethyl acetate, separating the organic layer containing the desired compound after washing vodou">

Connection required, if necessary, may be further subjected to purification by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

STAGE A2

In this stage, the compound of formula (1a), which is a compound of the present invention, is obtained by treatment of compounds of formula (3) reagent, which can remove the t-butoxycarbonyl group, in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. Special restrictions on the nature of the solvent to be used, does not exist, provided that it has no adverse effect on the reaction or involved in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol or ethanol; water; or a mixture of any two or more of them.

Similarly, there is no particular restriction on the nature of the reagents used to remove t-butoxycarbonyl group, and it also can be used by any reagent commonly used rst acid catalyst, can be used, for example acid Bronsted, such as an inorganic acid (e.g. hydrochloric acid, Hydrobromic acid, sulfuric acid, Perlina acid or phosphoric acid) or organic acid (e.g. acetic acid, formic acid, oxalic acid, methanesulfonate acid, p-toluene-sulfonic acid, triperoxonane acid or triftormetilfullerenov acid), preferably an organic acid (particularly acetic acid or triperoxonane acid).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents, bases and solvents. However, provided that the reaction is carried out in the PDF, more preferably from 1 to 5 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting includes: a neutralization reaction solution and purification of the residue obtained by distillation of the solvent under reduced pressure, chromatography on silica gel.

In the case when R2aor R3ais hydroxyamides group, Xarepresents a protected hydroxy group, or Wais carboxyamide group, the compound of the present invention further can be obtained by removing these protecting groups.

The reaction used to remove the protecting groups can vary, depending on the nature of the protecting group. However, it can be done in a standard way, for example, by the method described in "Protective Groups in Organic Synthesis", Second Edition (written by Greene and Wuts, John Wiley & Sons, Inc., published in 1991), which is here referred to.

When the hydroxy-protecting group is trialkylsilyl group, such as t-butyldimethylsilyl group, preferably it is possible to use acetic acid in a mixture of water and t is I diphenylmethylene group, you can use catalytic reduction using gas-hydrogen and a catalyst such as palladium black in a mixture of methanol and tetrahydrofuran, triperoxonane acid phenol, acetic acid as the acid and solvent, or complex trevormoran-diethyl ether to acetic acid.

METHOD B

In this Method, the compound of formula (1) is produced by interaction of the compounds of formula (2) with ammonia or hydroxylamine, which can be substituted by an alkyl group having from 1 to 4 carbon atoms in the amino-part, optionally with subsequent removal of the protection.

< / BR>
In the above formulas, R1, R2, R3, R2a, R3aX, Y, W, Z, Xaand Waare as defined above.

Stage B1

In this stage, the compound of formula (4) is produced by interaction of the compounds of formula (2) with tianyoude reagent in an inert solvent. The reaction is normally and preferably carried out in the presence of a solvent. Special restrictions on the nature of the solvent to be used, does not exist, provided that it has no adverse effect on the reaction or involved in the reaction reagents and that he can restoe as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and onomatology ether of ethylene glycol (methyl of Cellosolve "Cellosolve" is a trade mark); amides, such as formamide, dimethylformamide, dimethyl-acetamide", she methyl-2-pyrrolidone, methylpyrrolidinone and triamide hexamethylphosphoric acid, and sulfoxidov, such as dimethyl sulfoxide and sulfolane. Among them, preferred alcohols (particularly methanol).

There is also no particular restriction on the nature of the used tianyoude agents, and any tianyoude agent commonly used in reactions of this type can be used here equally. Examples of such tianyoude agents include CYANOGEN bromide, in the case of which, at the same time, as the basis of using sodium acetate.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50o

After completion of the reaction, the desired compound can, for example, to allocate using chromatography on silica gel to purify the residue obtained by distillation of the solvent.

STAGE B2

In this Stage, the compound of formula (1), which is a compound of the present invention, is produced by interaction of the compounds of formula (4) with ammonia or hydroxylamine, which can be substituted by an alkyl group having from 1 to 4 carbon atoms in the amino-part, optionally with subsequent removal of the protection,

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or involved in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include perature reaction is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents, bases and solvents. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method of isolation involves the use of chromatography on silica gel to purify the residue obtained by distillation of the solvent.

In the case where R2aor R3arepresents a hydroxy-protecting group, Xarepresents a protected hydroxy group, or Warepresents carboxy-zashishayu group, the compound of the present invention can >In this Method, the compound of formula (1c) is produced by interaction of the compounds of formula (5) with allermuir agent, followed by removal of the protection.

< / BR>
In the above formulas:

R1, R2, R3, W, Z, and Wasuch as defined above;

R5represents a halogen atom, aliphatic, acyloxy group having from 2 to 25 carbon atoms, or alkoxy group having from 1 to 4 carbon atoms.

STAGE C1

In this Stage, the compound of formula (6) is obtained by introduction of the desired acyl group in the compound of the formula (5) in an inert solvent.

The method of acylation can be carried out on any of the following Methods 1, 2 and 3.

Method 1

In this Method, the compound of formula (5) is subjected to interaction with the compound of the formula RCO-L or a compound of the formula RCO-O-COR where R is alkyl group having from 1 to 24 carbon atoms; and L represents tsepliaeva group. Special restrictions on the nature of the used tseplyaesh groups does not exist, and it can be used equally any nucleophilic tsepliaeva group commonly used in reactions of this type. Examples of such tseplyaesh groups include: atoms, alkoxy part, such as methoxycarbonylamino, ethoxycarbonyl group; halogenated, alkanoyloxy groups, such as chloroacetoxy, dichloracetate, trichloroacetoxy, triptoreline group; alkanesulfonyl group having from 1 to 6 carbon atoms in the alkyl part, such as methanesulfonate, econsultancy group; halogenated, alkanesulfonyl group having from 1 to 6 carbon atoms in the alkyl part, such as tripterocalyx, pentafluoroethanesulfonyl group; and arylsulfonate groups, such as benzosulfimide, p-toluensulfonate and p-nitrobenzenesulfonyl group. Among them, preferred halogen atoms, halogenated, alkanesulfonyl group, arylsulfonate group.

The reaction may proceed in the presence or absence of a base and in a solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or involved in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents clolour and xylene; halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl, butyl acetate and diethyl carbonate; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; NITRILES, such as acetonitrile and isobutyronitrile; and amides, such as formamide, dimethylformamide, dimethylacetamide, methyl-2-pyrrolidone, methylpyrrolidinone and triamide hexamethylphosphoric acid.

Special restrictions on the nature of the used grounds also does not exist, and it can be used equally any base commonly used in reactions of this type. Examples of such bases include: organic bases, such as methylmorpholine, triethylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, methyl-piperidine, pyridine, 4-pyrrolidinedione, picoline, 4-( dimethylamino)pyridine, 2,6-di(t-butyl)-4-methylpyridine, quinoline, dimethylaniline and diethylaniline.

4-( Dimethylamino)pyridine and 4-pyrrolidinone can be used in catalytic quantities in combination with one or more other: Quaternary ammonium salts, such as chloride of benzyltriethylammonium and tetrabutylammonium chloride; and crown ethers such as dibenzo-18-crown-6.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -20oC to the boiling point of the used solvent, more preferably from 0oC to the boiling point of the used solvent. The time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents, bases and solvents. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 10 minutes to 3 days, more preferably from 1 hour to 6 hours.

Method 2

In this Method, the compound of the formula: RCOOH [where R is as defined above] is subjected to interaction with the compound of the formula (5) in the presence of Asteri the operation can also be carried out in the presence of a condensing agent.

Special restrictions on the nature of the used esterificados agents does not exist, and it also can be used any esterificados agent commonly used in reactions of this type. Examples of such esterificados agents include active esters, especially alkyl californiathe, such as methyl chloroformate and ethyl chloroformate; and diesters cyanophosphonate acid such as the diethyl cyanoformate. Esterification with such active esters proceeds in the presence of at least one condensing agent. Specific examples of such condensing agents include hydroxy derivatives, such as hydroxysuccinimide, 1-hydroxybenzotriazole and hydroxy-5-norbornene-2,3-dicarboximide; disulfide compounds such as 2,2'-dipyridyl disulfide; compounds, succinic acid, such as disuccinimidyl carbonate; compounds, phosphinic acid chloride of the acid such as the acid chloride of bis(2-oxo-3-oxa-aridisol)phosphinic acid; oxalate derivatives, such as disuccinimidyl oxalate (DSO, DSO), depthlimit-oxalate (DFO DPO), bis(norbornadiene) -oxalate (BNO, BNO), 1,1'-bis(benzotriazolyl) oxalate (BTO, WTO), 1,1'-bis(6-chlorobenzotriazole) oxalate (BTBO, ESPO) and livostin, dialkyl azodicarboxylate-triarylphosphine, in which the alkyl part has from 1 to 6 carbon atoms, such as diethyl-azodicarboxylate-triphenylphosphine; alkyl - 5-arylisocyanate (isoxazolium)-3'-sulfonates in which the alkyl part has from 1 to 6 carbon atoms, such as ethyl - 5-phenylisoxazole-3'-sulfonate; carbodiimide derivatives, including dicyclohexylcarbodiimide, such as dicyclohexylcarbodiimide (DCC, DCC) and 1-ethyl-3- (3-dimethylaminopropyl)carbodiimide (ADPC, EDAPC); deteroriated, such as di-2-pyridylmethylene; arylsulfonate, such as p-nitrobenzenesulfonate; halides 2-halo-1-alkylpyridine, in which the alkyl part has from 1 to 6 carbon atoms, such as iodide 2-chloro-1-methylpyridine; directorrelated, such as diphenylphosphoryl (DFFA, DPPA); imidazole derivatives such as 1,1'-oxalylamino and carbonyldiimidazole; derivative benzotriazole, such as 1-hydroxybenzotriazole (HOBT, HOBT); and derivatives of dicarboximide, such as hydroxy-5-norbornene-2,3-dicarboximide (HONB), preferably directorrelated.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature espolio reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane and heptane; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl, butyl acetate and diethyl carbonate; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; NITRILES, such as acetonitrile and isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide, methyl-2-pyrrolidone, methylpyrrolidinone and triamide hexamethylphosphoric acid.

Special restrictions on the nature of the used grounds also does not exist, and can be used equally any base commonly used in reactions of this type. Examples of such bases include bases described in relation to Method 1, above.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. Preferred temperatureto or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -20 to 80oC, more preferably from 0oC to room temperature. The time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 10 minutes to 3 days, more preferably from 30 minutes to 1 day.

Method 3

In this Method, the compound of the formula: RCOOH [where R is as defined above] is subjected to interaction with the compound of the formula (5) in the presence of dialkylamide ether, halogenated phosphoric acid, such as diethyl-chlorophosphate, and base in a solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: alipay; halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl, butyl acetate and diethyl carbonate; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; NITRILES, such as acetonitrile and isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide, methyl-2-pyrrolidone, methylpyrrolidinone and triamide hexamethylphosphoric acid.

Special restrictions on the nature of the used grounds also does not exist, and can be used equally any base commonly used in reactions of this type. Examples of such bases include bases described in relation to Method 1, above.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperature is the temperature to 50oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 10 minutes to 3 days, more preferably from 30 minutes to 1 day.

The number of input acyl groups varies depending on the number Alliluyeva agent.

After completion of the reaction according to any one of the aforementioned Methods, the desired compound of formula (6) can be isolated from the reaction mixture in a standard way. For example, the desired compound can be obtained by the following procedure: the appropriate neutralizing the reaction mixture; adding an immiscible with water, an organic solvent, such as ethyl acetate, there after removing insoluble substances, if necessary, by filtration; washing with water; separating the organic layer containing the desired compound; drying the organic layer over anhydrous magnesium sulfate; the distillation of the solvent.

The compound thus obtained can be separated and oresident or other methods, usually used for separation and purification of organic compounds, for example: adsorption column chromatography, which is used as a carrier, such as silica gel, aluminum oxide or gel of magnesium silicate (such as supplied under the trademark of "Florisil"); the way in which use synthetic (synthesis) adsorbing agent, such as a distribution chromatography using a carrier such as Sephadex LH-20 (trade mark substances produced by Pharmacia Co., Ltd.), Amberlite XAD-11 (trade mark substances produced by Rohm & Haas Co., Ltd.) or Diaion HP-20 (trademark substances produced by Mitsubishi Kasei Co., Ltd.); or column chromatography with normal or reversed phase (preferably liquid chromatography high resolution), using silica gel or alkilirovanny silica gel and elution with a suitable eluent.

Stage C2

In this Stage, the compound of formula (1c), which is a compound of the present invention, is obtained by treatment of compounds of formula (6) reagent, which can remove the t-butoxycarbonyl group. The reaction is normally and preferably carried out in the presence of an inert solvent.

This reaction is basically the same as the can A.

When Warepresents a carboxy-protecting group, the compound of the present invention can be obtained by subsequent removal of these protecting groups, as described in Stage A2.

Method D

This Method illustrates obtaining the compounds of formula (2a), which is one of the starting compounds used in the Methods A and B.

< / BR>
In the above formulas:

R1, R5, Z and Wasuch as defined above;

R4represents a hydrogen atom, acetoxy group or an alkoxy group having from 1 to 4 carbon atoms;

Ac represents acetyl group;

Boc represents t-butoxycarbonyl group; and

Me represents a methyl group.

Stage D1

In this Stage, the compound of formula (8) is produced by interaction of the compounds of formula (7) with a base in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable the automatic hydrocarbon, such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; and alcohols, such as methanol. Among them, preferred halogenated hydrocarbons and methanol.

Special restrictions on the nature of the used grounds also does not exist, provided that it does not affect other functional groups (for example, methyl group of ester), and any base commonly used in reactions of this type, equally can be used here. Examples of such bases include methoxide alkali metals, such as sodium methoxide and potassium methoxide.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at a temperature of from to register, depending on many factors, particularly the reaction temperature and the nature of the reagents, bases and solvents. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting comprises: neutralizing the reaction solution with a solution of hydrogen chloride in dioxane; the distillation of the solvent under reduced pressure and purification of the residue, thus obtained, using chromatography on silica gel.

Stage D2

In this Stage, the compound of formula (9) is produced by interaction of the compounds of formula (8) with a reagent for introducing isopropylidene group.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some train and petroleum ether; aromatic hydrocarbons, such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone. Among them, preferred ketones, especially acetone).

The reagent used to introduce isopropylidene group is preferably 2,2-dimethoxypropane. The reaction is usually carried out in the presence of acid, such as p-toluensulfonate acid as a catalyst.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also widely marinovaniya and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting comprises: adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the reaction solution, extraction of the desired compound in a solvent such as ethyl acetate; and the distillation of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage D3

This stage can be performed, if necessary, by:

1) the conversion of a methyl group of an ether carboxylic acid to another Deputy;

2) hydrolysis of the ether carboxylic acids; or

3) run the above 2) and then obtained the security of a free carboxylic acid.

1. The transformation of ester

In E. in order to give the desired ester group, in the presence of a base in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, the cyclohexanol and onomatology ether of ethylene glycol (such as supplied under the trade mark "of Methyl Cellosolve"). Among them, preferred alcohols, which form the desired ester group.

the second degree any cause, commonly used in reactions of this type. Examples of such bases include organic bases, such as pyridine, triethylamine, diethylamine and 4 - dimethylaminopyridine.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting comprises: neutralizing the reaction mixture with acid; adding a water-immiscible solvent such as ethyl acetate; the extraction of the desired compound in a solvent such as ethyl acetate; washing the extract and distillation of the solvent. Further, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography, if necessary.

The same compound of the formula (10) can also be obtained by the interaction of the carboxylic acid [obtained by removal of the methyl group of the compounds of formula (9)] with alcohol of the formula Wd-OH, or alkylhalogenide formula Wd-Hal (where Wdrepresents an alkyl group and Hal represents a halogen atom).

2. Hydrolysis

In this stage, the compound of formula (10) receive doctitle carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include water or a mixture of water and one or more organic solvents. Such suitable organic solvents are: alcohols, such as methanol and ethanol; and ethers, such as diethyl ether, tetrahydrofuran and dioxane. Among these solvents, preferred is water or a mixture of water and one or more alcohols.

Special restrictions on the nature of the used grounds also does not exist, and can be used equally any base commonly used in reactions of this type. Examples of such bases include hydroxides of alkali metals such as sodium hydroxide and potassium hydroxide. The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and the nature of the source of the substance or reagent. occhialino from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents, bases and solvents. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting includes: adding Dowex-50x8 (H+type) (Dowex is a trademark) to the reaction solution for neutralization, distillation of the solvent under reduced pressure and purification of the thus obtained residue by chromatography on silica gel.

3. Diphenylmethylsilane

In this Stage, the compound of formula (10) is produced by interaction diphenyldiazomethane with the compound of the formula (9) in the presence of a Lewis acid in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the solvent used, provided that he has not the least to a certain extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, the cyclohexanol and onomatology ether of ethylene glycol (such as supplied under the trade mark "of Methyl Cellosolve"). Among them, preferred alcohols (particularly methanol), halogenated hydrocarbon (particularly dichloromethane), and mixtures thereof.

The Lewis acid, which is commonly used in this reaction, preferably represents a complex of boron TRIFLUORIDE - diethyl ether.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature is usually Savino, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably at room temperature. The time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent.

However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 10 minutes to 5 hours, more preferably from 1 to 3 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting includes: adding an acid, such as acetic acid, to the reaction mixture; the distillation of the solvent and purification of the residue via recrystallization or chromatography.

Stage D4

In this Stage, the compound of formula (11) are obtained from the compounds of formula (10), using a reducing agent in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it does not OK the at least to a certain extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; alcohols, such as methanol, ethanol, propanol, isopropanol, butanol, Isobutanol, t-butanol, isoamyl alcohol, diethylene glycol, glycerin, octanol, cyclohexanol and onomatology ether of ethylene glycol (such as supplied under the trade mark "of Methyl Cellosolve"); ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone, isophorone and cyclohexanone; NITRILES, such as acetonitrile and isobutyronitrile; amides, such as formamide, dimethylformamide, dimethylacetamide, methyl-2-pyrrolidone, methylpyrrolidinone and triamide hexamethylphosphoric acid; sulfoxidov, such as dimethyl sulfoxide and sulfolane; fatty acids, such as acetic acid; and a mixture of water and any one or more of these organic solvents. Among them, preferred alcohols (particularly methanol), ethers such as tetrahydrofuran and dioxane, and fatty acids, such as acetic sour is the nature of the used reducing agents, and it also can be used by any reducing agent commonly used in reactions of this type. Examples of such reducing agents include hydrogenation catalyst such as palladium-on-carbon, platinum or Raney Nickel, in the presence of a gas - hydrogen. Especially preferably using Lindlar catalyst (Pd-BaSO4or Pd-CaCO3and the quinoline or lead acetate in combination).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, is usually sufficient period of time from 15 minutes to 10 hours, more than before the R, by filtering the reaction solution under reduced pressure to remove the catalyst and distillation of the solvent under reduced pressure. Further, if necessary, the desired compound can be cleaned by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage D5

In this Stage, the compound of formula (2a) is obtained by removal of the protecting isopropylidenebis group of compounds of formula (11) in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: halogenated hydrocarbons, such as methylene chloride or chloroform.

The reagent used to remove protection isopropylidene group, preferably the acid. There is no particular restriction on the nature of the used acids, and it also can be used in the s of such acids include acid Bronsted, such as inorganic acids (e.g. hydrochloric acid, Hydrobromic acid, sulfuric acid, Perlina acid or phosphoric acid) or organic acids (e.g. formic acid, oxalic acid, methanesulfonate acid, p-toluensulfonate acid, triperoxonane acid or triftormetilfullerenov acid; a Lewis acid such as zinc chloride, tin tetrachloride, trichloride boron TRIFLUORIDE boron or tribromide boron; and acidic ion-exchange resin. Which one is preferable organic acids (in particular, triperoxonane acid).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. But what of catachan period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method of isolation include: neutralization of the reaction solution and distillation of the solvent under reduced pressure. Further, if necessary, the desired compound can be cleaned by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Method E

In method E obtain the connection formula (2b) or the compound of the formula (2c), which are among the starting compounds, which can be used in Method A or B.

< / BR>
In the above formulas:

R1, Z and Wasuch as defined above;

R5arepresents a hydroxy group; and

R6represents an aliphatic acyl group having from 2 to 25 carbon atoms.

Stage E1

At this Stage, get the connection formula (12) by introducing the desired acyl group in the compound of the formula (10a) in an inert solvent.

This reaction is basically the same as and may be the same R> At this Stage, get the connection formula (13) by removing the protection isopropylidenebis group of compounds of formula (12) in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D5 Method D.

Stage E3

At this Stage, get the connection formula (2b) of the compounds of formula (13), using a reducing agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D4 Method D.

Stage E4

At this Stage, get the connection formula (14) by treating the compounds of formula (12) with a reagent which removes isopropylidene group in the presence of an acid catalyst and in a suitable solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some who simultaneously acts as acid catalyst).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 10 to 70oC, more preferably from 30 to 60oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 24 hours, more preferably from 10 to 20 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method of isolation include: distillation of the solvent under reduced pressure; adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the reaction solution, extraction of the desired connection is my connection can be cleared by recrystallization or by using different types of chromatography such as column chromatography or preparative thin layer chromatography.

Stage E5

At this Stage, get the connection formula (2c) of the compounds of formula (14), using a reducing agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D4 Method D.

Method F

In Method F receive the connection formula (2d) or a compound of the formula (2e), which are among the starting compounds used in the Methods A and B.

< / BR>
In the above formulas:

R1, R3a, R6, Z and Wasuch as defined above;

R2bis hydroxyamides group, preferably t-butyldimethylsilyloxy group; and

R7represents an aliphatic acyl group having from 2 to 25 carbon atoms.

The F1 stage

At this Stage, get the connection formula (15) by reacting with the compound of the formula (14) with a reagent, which protects the primary hydroxy group in an inert solvent.

There is no particular restriction on the nature of the protecting group, provided that it can with izumisawa group, usually used in organic synthesis. Examples of such groups include trialkylsilyl, dialkylanilines and alkyldiphenylamine groups such as t-butyl dimethylsilicone group and t-butyldiphenylsilyl group.

Similarobama can be performed by any standard method. For example, similarobama can be carried out by reacting the compounds of formula (14) with t-butyldimethylsilyl a halide (particularly chloride) in the presence of a base such as triethylamine or 4-( dimethylamino)pyridine, in a solvent such as dimethylformamide.

The reaction may proceed in a wide range of temperatures and the precise temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 40oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that d is hours, more preferably from 10 to 20 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting comprises: adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the reaction solution, extraction of the desired compound with a suitable solvent, such as ethyl acetate, and the Stripping of the solvent. Further, if necessary, the desired compound can be cleaned by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage F2

At this Stage, get the connection formula (16) by introducing the desired acyl group in the compound of formula (15) in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage C1 Method C.

Stage F3

At this Stage, get the connection formulas (17) the interaction of the compounds of formula (16) with a reagent which removes the protecting group of doritis. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol and ethanol; water, or a mixture of any two or more of these solvents.

There is no particular restriction on the nature of the used agents that remove the protection, and it also can be used to remove the protecting agent commonly used in reactions of this type. Examples of such removed protection agents include acid. The nature of this acid is not critical, and there can be used any acid commonly used in standard reactions as acid catalyst. Examples are: acid Bronsted, such as inorganic acids (for example, chlorotoluron acid, Hydrobromic acid, sulfuric acid, Perlina acid and phosphoric acid) and organic acids such as acetic acid, formic acid, oxalic acid, methanesulfonate acid, p-toluensulfonate acid, triperoxonane acid and CryptoMemory and tribromide boron; and acidic ion-exchange resin. Which one is preferable organic acids (particularly acetic acid and triperoxonane acid).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method of isolation include: neutralization of the reaction solution; the distillation of the solvent under reduced pressure the acyl group (R7in the 8-position is shifted to the 9-position.

If needed, the reagent for the formation of Floridiana, such as tetrabutylammonium fluoride, can be used as removing the protecting agent.

Stage F4

This Stage can be done by:

1) acylation of the hydroxy group at the 8-position; or

2) protecting the hydroxy group.

The reaction of stage 1 is essentially the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage C1 Method C.

Reaction stage 2) can be carried out using t-butyldimethylsilyl triflate as a reagent for introduction of a protecting group and using lutidine as a base, in methylene chloride as solvent.

Stage F5

At this Stage, get the connection formula (2d) of the compounds of formula (18), using a reducing agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D4 Method D.

Stage F6

At this Stage, get the connection formula (2e) of the compounds of formula (16), AI can be carried out in the same manner, as and using the same reagents and reaction conditions as in Stage D4 Method D.

Method G.

In Method G get the connection formula (2f) or the compound of the formula (2g), which are among the starting compounds used in the Methods A and B.

< / BR>
< / BR>
In the above formulas:

R1, R6, Z and Wasuch as defined above; and

R8represents an aliphatic acyl group having from 2 to 25 carbon atoms.

Stage G1

At this Stage, get the connection formula (19) by introducing the desired acyl group in the compound of formula (13) in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage C1 Method C.

Stage G2

At this Stage, get the connection formula (2f) of the compounds of formula (19), using a reducing agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D4 Method D.

Stage G3

At this Stage, get the connection forms which This reaction, basically, the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage C1 Method C.

Stage G4

At this Stage, get the connection formula (2g) of the compounds of formula (20), using a reducing agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D4 Method D.

Method H

In Method H obtain the connection formula (5), which is among the starting compounds used in the Method C

< / BR>
In the above formulas:

R1, R4, R5, Z, Wa, Ac, Boc, and Me are such as defined above;

Xcrepresents an alkoxy group having from 1 to 4 carbon atoms; and

Bz represents a benzyl group.

Stage H1

At this Stage, get the connection formula (22) by the interaction of alkylhalogenide with the compound of the formula (21) [described in Carbohydrate Research, 83, 163 - 169 (1980)] in the presence of a base in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is not a special ograniczona participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; amides, such as formamide, dimethylformamide, dimethylacetamide, methyl-2-pyrrolidone, methylpyrrolidinone and triamide hexamethylphosphoric acid; sulfoxidov, such as dimethyl sulfoxide and sulfolane. Of them preferred amides (particularly dimethylformamide).

Special restrictions on the nature of the used grounds also does not exist, and can be used equally any base commonly used in reactions of this type. Examples of such bases include hydrides of alkali metals such as lithium hydride, sodium hydride and potassium hydride; alkoxides of alkali metals such as sodium methoxide, ethoxide sodium, potassium methoxide, ethoxide potassium t-piperonyl potassium and lithium methoxide; mercaptans alkali metals, such as methylmercaptan sodium and ethyl mercaptan sodium; organic bases, such as methylmorpholine, 4-pyrrolidinedione, picoline, 4-( dimethylamino)pyridine, 2,6-di(t-butyl)-4-methylpyridine, quinoline, dimethylaniline, diethylaniline, 1,5-diazabicyclo[4.3.0] non-5-ene (DBN, DBN), 1,4-diazabicyclo- [2.2.2] octane (DABCO) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU); and organic base metals, such as utility, lithium diisopropylamide and lithium bis (trimethylsilyl)amide. Of them preferred hydrides, alkali metal (especially sodium hydride).

Special restrictions on the nature of the used alkylhalogenide also does not exist, and it also can be used any alkylhalogenide commonly used in reactions of this type. Preferred such alkylhalogenide are were synthesized and alkalinity.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent and the nature of the source of the substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 0oC to 50oC, more preferably at about room temperature. The time required for the reaction may also widely paronomasia and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 24 hours, more preferably from 2 to 10 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting comprises: adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the reaction solution, extraction of the desired compound with a suitable solvent, such as ethyl acetate; and the distillation of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage H2

In this Stage, the compound of formula (23) are obtained by reacting a reducing agent with a compound of formula (22) in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, when usloviiakh reagents, at least to some extent. Examples of suitable solvents include: alcohols, such as methanol, ethanol; ethers, such as tetrahydrofuran and dioxane; fatty acids, such as acetic acid; or a mixture of any one or more of these organic solvents and water. Of these, acetic acid is preferred.

Recovery is preferably carried out using hydrogen in the presence of a hydrogenation catalyst. There is no specific limitation on the nature of the used hydrogenation catalysts, and it also can be used any hydrogenation catalyst commonly used in reactions of this type. Examples of hydrogenation catalysts include palladium-on-carbon, platinum and Raney Nickel, preferably palladium-on-carbon.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 0oC to 50oC, more p is to reroute, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 24 hours, more preferably from 2 to 10 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting includes: removal of the hydrogenation catalyst by filtration, distillation of the solvent and purification of the thus obtained residue by recrystallization or by using various types of chromatography.

Stage H3

At this Stage, get the connection formula (24) by reacting sodium pyruvate with the compound of the formula (23) in the presence of aldolase acetylneuraminic acid and of sodium azide in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at the ü in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 0oC to 50oC, more preferably at about room temperature. The time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 5 hours to 5 days, more preferably from 1 to 3 days is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method of isolation include: desalination connection using a cation exchange resin and purification of compounds using chromatography using anion-exchange resin.

Stage H4

At this Stage, get the connection formula (25) esterifications the compounds of formula (24) in the presence of CII equally can be used any acid, usually used as an acid catalyst in reactions of this type. Examples of such acids include acid Bronsted, such as inorganic acids (e.g. hydrochloric acid, Hydrobromic acid, sulfuric acid, Perlina acid or phosphoric acid) or organic acids (e.g. acetic acid, formic acid, oxalic acid, methanesulfonate acid, p-toluensulfonate acid, triperoxonane acid or triftormetilfullerenov acid; a Lewis acid such as zinc chloride, tin tetrachloride, trichloride boron TRIFLUORIDE boron or tribromide boron; and cation exchange resin. Of them preferred cation exchange resins.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 0oC to 50oC, more preferably at about room temperature. The time required for the reaction may also widely variostream. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 1 to 48 hours, more preferably from 5 to 24 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in the usual way. For example, one suitable method for detecting includes: removing the cation exchange resin by filtration, distillation of the solvent and purification of the thus obtained residue by recrystallization or by using various types of chromatography.

Stage H5

In this Stage, the compound of formula (25) acelerou in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage C1 Method C.

Stage H6

In this Stage, the compound obtained in Stage H5, glorious by reacting the compound obtained in Stage H5, hydrogen chloride in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it is not provided is ina least to a certain extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol. Of these preferred esters (in particular, dioxane).

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 0oC to 50oC, more preferably at about room temperature. The time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 5 hours to 2 days, more predpochtitel distilled off under reduced pressure and the product is used, as such for the next reaction.

Stage H7

In this Stage, the compound of formula (26a) is produced by interaction of the base with the compound obtained in Stage H6, to carry out the dehydrochlorination.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol. Of these preferred aromatic hydrocarbons (particularly benzene).

Special restrictions on the nature of the used grounds also does not exist, and can be used equally any base commonly used in reactions of this type. Examples of such bases include alkoxides of Molochny the ID of lithium; mercaptans of alkali metals, such as methylmercaptan sodium and ethyl mercaptan sodium; organic bases, such as methylmorpholine, triethylamine, Tripropylamine, tributylamine, diisopropylethylamine, dicyclohexylamine, methyl-piperidine, pyridine, 4-pyrrolidinedione, picoline, 4-( dimethylamino)pyridine, 2,6-di(t-butyl)-4-methylpyridine, quinoline, dimethylaniline, diethylaniline, 1,5-diazabicyclo-[ 4.3.0]non-5-ene (DBN, DBN), 1,4-diazabicyclo[2.2.2] octane (DABCO) and 1,8-diazabicyclo[5.4.0]-undec-7-ene (DBU), preferably DBU.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from 0oC to 50oC, more preferably at about room temperature.

The time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in prepost 10 to 24 hours, usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting comprises: adding a water-immiscible solvent, such as methylene chloride, and an aqueous solution of ammonium chloride to the reaction solution, extraction of the desired connection and the Stripping of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage H8

In this Stage, the compound of formula (27) are obtained by reacting the compounds of formula (26a), obtained as described in Stage H7, or other compounds of formula (26), which can be obtained as described in W0 95/32955, with aidarous (azidating agent in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve avodart, such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride and chloroform; ethers such as ether, tetrahydrofuran, dioxane and dimethoxyethane, and NITRILES, such as acetonitrile.

Special restrictions on the nature of the used aidarous agents also does not exist, and it can be used equally any aidarous agent commonly used in reactions of this type. Examples of such aidarous agents include derivatives azide diarylphosphino acid, such as azide diphenylphosphinic acid; triallelic azides, such as trimethylsilyl azide and triethylsilyl azide; and alkali metal azides such as sodium azide and potassium azide. Of them, preferable sodium azide.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10oC to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also Shir is hentov and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting comprises: neutralizing the reaction solution with a solution of hydrogen chloride in dioxane; the distillation of the solvent under reduced pressure and purification of the thus obtained residue by chromatography on silica gel.

Stage H9

In this Stage, the compound of formula (28) are obtained by reacting the compounds of formula (27) with t-butoxycarbonylamino agent in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aromatic hydrocarbons, such as benzene, colortemperature, dioxane and dimethoxyethane, and amides, such as dimethylformamide.

t-Butoxycarbonylamino can be carried out by reacting di-t-butyl dicarbonate or 2-(t-butoxycarbonyloxyimino) -2-phenylacetonitrile in the presence of a base, such as 4-( dimethylamino)pyridine.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting includes: a neutralization reaction solution; the distillation of the solvent under reduced pressure; adding a water-immiscible solvent such as ethyl acetate, and water to the residue; the extraction of the desired compound with a suitable solvent, such as ethyl acetate; and the distillation of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage H10

In this Stage, the compound of formula (29) are obtained by reacting the compounds of formula (28) with a base in an inert solvent.

This reaction is basically the same as and may be carried out by those who>Stage H11

In this Stage, the compound of formula (29) will acetimidoyl in an inert solvent.

Acetylation can be carried out in a standard way, usually used to protect the hydroxy group. For example, acetylation can be carried out 1) by reacting the compounds of formula (29) with acetic anhydride in pyridine or 2) by reacting the compounds of formula (29) with acetyl-halide (especially chloride) in the presence of a basic catalyst (e.g. triethylamine, dimethylaminopyridine) in methylene chloride.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting includes: a neutralization reaction solution; the distillation of the solvent under reduced pressure; adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the residue; the extraction of the desired compound with a suitable solvent, such as ethyl acetate; and the distillation of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatogaphy (30) is obtained by processing the connection, obtained in Stage H11, with a reagent which eliminates t-butoxycarbonyl group, in an inert solvent.

Elimination of t-butoxycarbonyl group can be done in the usual way.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvent, provided that it has no adverse effect on the reaction or on participating in the reaction reagents and that it can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; esters such as ethyl formate, ethyl acetate, propyl, butyl acetate and diethyl carbonate; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol; amides, such as formamide, dimethylformamide, dimethylacetamide, methyl-2-pyrrolidone, methylpyrrole-Denon ctically halogenated hydrocarbons (particularly methylene chloride).

Special restrictions on the nature of the reagent used for the elimination of the t-butoxycarbonyl group does not exist, and it also can be used by any agent commonly used in reactions of this type. An example of such a reagent is hydrochloric acid.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at temperatures from -10 to 50oC, more preferably from 10 to 30oC. the Time required for the reaction may also vary widely, depending on many factors, particularly the reaction temperature and the nature of the reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 24 hours, more preferably from 1 to 10 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture standardem pressure; adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the reaction solution, extraction of the desired compound with a suitable solvent, such as ethyl acetate; and the distillation of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage H13

In this Stage, the acyl group is introduced into the compound of the formula (30) by reaction with allermuir agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage C1 Method C.

Stage H14

In this Stage, the compound of formula (31) are obtained by reacting the compound obtained in Stage H13, with a reagent that converts the carbonyl group, thiocarbonyl group in an inert solvent.

The reaction is normally and preferably carried out in the presence of a solvent. There is no specific limitation on the nature of the used solvents which can dissolve the reagents, at least to some extent. Examples of suitable solvents include: aliphatic hydrocarbons such as hexane, heptane, ligroin and petroleum ether; aromatic hydrocarbons such as benzene, toluene and xylene; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride, dichloroethane, chlorobenzene and dichlorobenzene; ethers, such as diethyl ether, diisopropyl ether, tetrahydrofuran, dioxane, dimethoxyethane and dimethyl ether of diethylene glycol. Of them preferred ethers (particularly tetrahydrofuran).

There is no particular restriction on the nature of the reagent used for the conversion of the carbonyl group in a thiocarbonyl group, and preferably is Lawesson''s reagent.

The reaction may proceed in a wide range of temperatures, and the precise reaction temperature is not essential for the invention. The preferred reaction temperature usually depends on such factors as the nature of the solvent, and used the original substance or reagent. However, in General, we found that the reaction is conveniently carried out at a temperature of from 10 to 100oC, more preferably from 40 to 70oC. the Time required for the reaction, ispolzuemykh reagents and solvent. However, provided that the reaction is carried out in the preferred conditions described in General terms above, the period of time from 15 minutes to 10 hours, more preferably from 1 to 5 hours is usually sufficient.

After completion of the reaction, the desired compound can be isolated from the reaction mixture in a standard way. For example, one suitable method for detecting comprises: adding a water-immiscible solvent such as ethyl acetate, and an aqueous solution of acid sodium carbonate to the reaction solution, extraction of the desired compound with a suitable solvent, such as ethyl acetate; and the distillation of the solvent. Further, if necessary, the desired compound can be purified by recrystallization or by using various types of chromatography, such as column chromatography or preparative thin layer chromatography.

Stage H15

In this Stage, the compound of formula (32) is obtained from the compounds of formula (31) by using a reducing agent in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D1 Method d

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage A1 of Method A.

Stage H17

In this Stage, the compound of formula (34) are obtained by reacting the compounds of formula (33), described later, with a base in an inert solvent.

This reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D1 of the Way D.

Stage H18

If necessary, this stage can be carried out by 1) conversion of the methyl group of ester of carboxylic acid in the other Deputy, 2) hydrolysis of ester carboxylic acid or 3) protect the carboxylic acid after the above stage 2).

The reaction is basically the same as and may be carried out in the same manner as and using the same reagents and reaction conditions as in Stage D3 Method D.

In some cases, the compounds of this invention can be effectively obtained by implementation of the above stages in a different order, which is obvious to the skilled reader.

Connection data and, diluents or adjuvants and in various combinations, as is well known in this field. For example, the compounds of this invention can be used orally or via the intranasal route in the form of a liquid preparation such as a solution or suspension (optionally in aqueous medium or in a mixture or the kind of environment and water co-solvent), or in the form of a spray or of the drug in powder form. Liquid preparations such as solutions, not necessarily including water co-solvent, can be prepared in a standard way, for example, using purified water, pharmaceutically acceptable organic solvent (e.g. ethanol, propylene glycol or PEG), stabilizing agent (peroxybenzoate, such as methylparaben or propylparaben; alcohol, such as chlorobutanol, benzyl alcohol or phenethyl alcohol; benzalkonium chloride; phenol, such as phenol or cresol; thimerosal; or dehydroacetic acid). Aerosols can be obtained in a standard way, using propellant, such as various gases, such as Chlorofluorocarbons (Freon) (trade mark) and the gas is nitrogen and surfactant, such as lecithin. Preparations in powder form can be obtained in a standard way, using any one or more of the organic fillers, including sugar derivatives such as lactose, sucrose, glucose, mannitol and sorbitol; starch derivatives such as corn starch, potato starch, a-starch, dextrin and carboxymethyl starch; cellulose derivatives such as crystalline cellulose, hydroxypropyl cellulose of low substitution hydroxypropylmethyl cellulose, carboxymethyl cellulose, calcium carboxymethyl cellulose and intermolecular-linked sodium carboxymethyl cellulose; gum Arabic; dextran & pullulan. Other fillers include inorganic fillers, including silicate derivatives such as soft silicon dioxide, synthetic aluminum silicate and aluminate of metasilicate magnesium; phosphates such as calcium phosphate; carbonates such as calcium carbonate; and sulfates such as calcium sulfate. Examples of lubricants include stearic acid; metal salts of stearic acid such as calcium stearate and magnesium stearate; talc; colloidal silica; waxes such as beeswax and Carnauba wax sperm whale (sperm whale); boric acid; adipic acid; sulfates such as sodium sulfate; glycol; fumaric acid; sodium benzoate; leucine; sodium salts of fatty acids; laurilsulfate, such as laurelwood derivatives of starch. Examples of stabilizing agents include: peroxybenzoate, such as methylparaben and propylparaben; alcohols such as chlorobutanol, benzyl alcohol and phenethyl alcohol; benzalkonium chloride; phenols such as phenol and cresol; thimerosal; dehydroacetic acid and sorbic acid.

Examples corrigentov include classtitle, acidifying agents and flavorings.

The number of the active component to be used, usually varies depending on symptoms, age and body weight of patient, but also on the method of application and the severity of the disease. However, in General, it is desirable to apply the active ingredient in an amount of from 0.1 mg / day, preferably 1 mg to 1000 mg (preferably 500 mg) in the case of liquid preparations; in the case of dry powder, the active ingredient is preferably used in an amount of from 0.1 mg / day, preferably 1 mg to 1000 mg (preferably 500 mg); in the case of aerosols, the active component is preferably used in an amount of from 0.1 mg / day, preferably 1 mg to 1000 mg (preferably 500 mg). It can be applied as a single dose or in divided doses, depending on the state.

BIOLOGICAL Aktivno sialidase-inhibitory activity and, in line with this, are useful for prevention and treatment of influenza. The activity of the compounds of the present invention is illustrated further by the following experiments.

Experiment 1

Inhibiting the replication of influenza virus activity

Strain A/Yamagata/32/89 (HINI) influenza virus multiplies rapidly in the living chicken (bird) eggs, and the virus obtained in this way, then put on a plate with MDCK cells (derived from kidney of the dog) to get platelets. MDCK cells infecting virus in the presence or absence of various concentrations of the test compounds. Inhibiting the replication of influenza virus activity of the test compounds can then be calculated by comparing the quantity of platelets in the control and test samples.

The methodology of this experiment is, in General, in accordance with Antimicrobial Agents And Chemotherapy, 17, pp.865 - 870 (1980).

In particular, MDCK cells cultivated in one confluent layer on the surface of Petri dishes with a diameter of 35 mm, the conditions of culturing MDCK cells on these plates represent the 37oC in a sterile atmosphere containing 5% V/V gas-carbon dioxide. After the merge cell culture gigastor, containing 50-100 Toya (pfu) (thrombocyte (platelet) - forming units) of the virus.

The resulting plate is then left to stand for 1 hour at 37oC to allow adsorption of the virus, and after this time the remaining phosphate buffered physiological saline solution is absorbed and it is replaced with MEM medium (Gibco BRL) containing 1 μg/ml of trypsin (Cooper Biomedical), 0.01% weight/weight DEAE dextran Pharmacia LKB), and 0.6% weight/weight of agar (Sigma) together with the test compound in an amount of from 0,00056 to 5.6 µg/ml.

Cultivation plates continue at 37oC for 40 hours in a sterile atmosphere containing 5% gas, carbon dioxide, and after this time utverzhdennuyu agar medium isolated. The dye crystal violet (Merck) dissolved in 19% methanol, obtaining a final concentration of 0.01%, and add to selected the agar to capture and stained cells, thus enabling to determine the number of platelets.

The number of platelets formed in the absence of the test compound, is taken as 100% (control). It is then possible to calculate 1C50(concentration in nm/ml, at which the test compound reduces the number of platelets by 50%), as Velich the present invention show high inhibitory replication of influenza virus activity, what is presented in Tables 3 and 4.

The compound A in the above Tables 3 and 4, as well as in Tables 5 and 6 below, is a compound obtained in Example 3, Toku-Hyo-Hei 5-507068. Its structure is presented below:

< / BR>
Experiment 2

Inhibiting sialidase influenza activity

In this experiment, the sample strain A/PR/8/34 (HINI) virus influenza is dissolved by using surface-active substances, after which the fraction of viral membrane purified by centrifugation. Cleared thus the fraction used as raw sialidase influenza virus, and as a substrate using p-nitrophenyl-N-acetylneuraminic acid (Wako Pure Chemical) to conduct tests similar to those described in Analytical Biochemistry, 94, 287- 296 (1979).

First get a solution of the enzyme, such that the resulting enzyme activity was 0,0011 units/ml (1 unit is that amount of enzyme which hydrolyzes 1 μmol of substrate in 1 minute). In addition, they receive beforehand aqueous solutions of the test compounds at various concentrations; aqueous substrate solution with a concentration of 33 μg/ml, and 20 mm buffer solution of 2 - (morpholino)econsultancy acid (pH 6.5) containing 50 mm chloride is th at 37oC for 20 minutes. The absorption of p-NITROPHENOL formed in the mixture was measured at 415 nm. The absorption measured at 415 nm when the mixture is produced by adding water instead of the aqueous solution of the test compound, taken as 100%. Thus, in order to measure inhibitory sialidase influenza activity, IC50(mm) is defined as the concentration of the sample at which the absorption is reduced by 50%.

These results are presented below in Table 5.

EXPERIMENT 3

Test for infection of mice

Previously getting the solution 1500 pfu adapted to mice of strain A/PR/8/34 influenza virus in 50 μl of 0.42% V/V phosphate buffer containing bovine serum albumin, and mice (BALB/C, female, age: 5-6 weeks, 20 g) infect dropwise, intranasal, obtained by the solution. The test compound suspended in physiological solution, getting a dose of 0.9 µmol/kg/50 ál. The obtained suspension is injected dropwise, intranasal, in the amount of 3 times, once for 4 hours before infection with the virus, once after 4 hours after infection and once after 17 hours after infection. The result is presented in terms of the number of mice surviving after 6 days, 8 days, 10 days and 15 days after infection. Tested the 6 below.

Thus you can see that the compounds of the present invention greatly increase the degree of survival of animals subjected to infection with influenza virus.

EXAMPLE 1

5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-7-O-hexanoyl - 2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

The compound N, 76-1)

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1 (i), Methyl 5-acetamido-4-azido-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate

7 g of 15.3 mmol) of methyl 5-acetamido-7,8,9-tri-acetyl-4 - azido-2,3,4,5-tetradeoxy glycero galacto-non-2 - topiramate dissolved in 20 ml of methanol, and the resulting solution was added dropwise 0.2 ml of 4.9 M methanolic solution of sodium methoxide (0.98 mmol), with stirring at room temperature. Then the reaction mixture was stirred at room temperature for 2 hours, after which it added dropwise 4 M solution of hydrogen chloride in dioxane, pH of the mixture was adjusted to a value of 6-7, and then the mixture is evaporated to dryness in a vacuum. The resulting residue is subjected to processing using column chromatography on silica gel using a 10:1 by volume mixture of methylene chloride and methanol as eluent, obtaining of 3.56 g (yield 69%) of the named compound as a colourless solid fast atom")

[]2D5+28,4o(to 0.21, methanol).

Spectrum of infrared absorption maxmax(cm-1): 2100, 1731, 1657.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 5.92 (1H, doublet, J = 2.3 Hz);

4,34 (1H, doublet of doublets, J = 9.3 and 2.5 Hz);

4,27 (1H, doublet of doublets, J = 10.7 and 1.2 Hz);

of 4.13 (1H, doublet of doublets, J = 10,8 and 9.4 Hz);

3,82 - to 3.92 (2H, multiplet);

with 3.79 (3H, singlet);

3,66 (1H, doublet of doublets, J = 11.4 and 5.0 Hz);

of 3.60 (1H, broad doublet, J = 9,3 Hz);

2,03 (3H, singlet).

1(ii) of Methyl 5-acetamido-4-azido-8,9-O-isopropylidene-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-topiramate

3.33 g (10.1 mmol) of methyl 5-acetamido-4-azido - 2,3,4,5-tetradeoxy glycero galacto-non - 2-topiramate [obtained as described in stage (i) above] dissolved in 10 ml of acetone, and added to the resulting solution of 3.7 ml of 2,2-dimethoxypropane (30.2 mmol) and 100 mg p-toluensulfonate acid 1 hydrate (0.52 mmol) under stirring at room temperature. The mixture is then stirred for 30 minutes. At the end of this time the reaction mixture is added 200 ml of ethyl acetate and 60 ml of a saturated aqueous solution of acid sodium carbonate, and the mixture is separated to separate the organization of the Nata sodium and then once with 50 ml saturated aqueous solution of sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure, obtaining the remainder. This residue was subjected to purification using column chromatography on silica gel using a 2:1 by volume mixture of ethyl acetate and hexane as eluent, getting 3,24 g (yield 87%) of the named compound as a colourless solid.

Rf = 0,38 (20:1 = methylene chloride: methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/z 371 (M++H).

[]2D5+160,93o(C = 0,32, CHCl3).

Spectrum of infrared absorptionmaxmax(cm-1): 2094, 1734, 1656.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,98 (1H, doublet, J 2.5 Hz);

to 5.66 (1H, broad doublet, J = 6,9 Hz);

4,32 - to 4.41 (1H, multiplet);

a 4.03 - to 4.28 (6H, multiplet);

3,81 (3H, singlet);

of 3.57 (1H, doublet of doublets, J = 7,9 and 5.2 Hz);

a 2.12 (3H, singlet);

of 1.66 (1H, singlet);

of 1.39 (3H, singlet);

of 1.36 (3H, singlet).

1 (iii) of Methyl 5-acetamido-4-azido-7-O-hexanoyl-8,9-O - isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - topiramate

1.35 g (3.65 mmol) of methyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate who give 490 mg (4,01 mmol) dimethylaminopyridine and 0.61 ml (4,37 mmol) hexanoyl chloride under stirring and cooling with ice. Then the reaction mixture was stirred at room temperature for 30 minutes, then added dropwise with ice cooling type of 0.56 ml of triethylamine. The mixture was then stirred at room temperature for another 2 days. To the resulting solution was added 200 ml of ethyl acetate and 100 ml of a saturated aqueous solution of acid sodium carbonate, and the mixture is separated, to separate the organic layer. The organic layer is washed three times, each time with 50 ml of a saturated aqueous solution of sodium chloride, and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure, obtaining the remainder. The residue was subjected to purification using column chromatography on silica gel using 100:1, by volume mixture of methylene chloride and methanol as eluent, getting to 0.69 g (yield 34%) of the named compound as a yellow oil.

Rf = 0,46 (20:1 = methylenechloride:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/z 469 (M++H).

[]2D5+87,7o(C = 0,26, CHCl3).

Spectrum of infrared absorptionmaxmax(cm-1): 2099, 1745, 1660.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,95 (1H, doubleyou, J = 9.0 and 2.7 Hz);

to 4.73 (1H, doublet of doublets, J = 10,4 and 1.7 Hz);

4,39 (1H, doublet of doublets, J = 11,4 and 6.1 Hz);

to 4.14 (1H, doublet of doublets, J = 12.3 and 6.3 Hz);

of 3.95 (1H, doublet of doublets, J = 8.8 and 6.2 Hz);

3,81 (3H, singlet);

3,40 (1H, doublet of doublets, J = 18,7 and 8.6 Hz);

2,28 - 2,52 (2H, multiplet);

2,02 (3H, singlet);

1,53 - 1,72 (2H, multiplet);

of 1.37 (3H, singlet);

of 1.35 (3H, singlet);

1,25 - of 1.43 (4H, multiplet);

0,86 - of 0.94 (3H, multiplet).

1 (iv) of Methyl 5-acetamido-4-amino-7-O-hexanoyl-8,9-O - isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - topiramate

650 mg (1.38 mmol) of methyl 5-acetamido-4-azido-7 hexanoyl-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (iii) above] dissolved in 20 ml of methanol, and to the resulting solution under stirring at room temperature add 400 mg of Lindlar catalyst. Then the reaction system dearyou and the air is replaced by hydrogen. Then the reaction mixture was stirred at room temperature for 2 hours, after which it was filtered under reduced pressure, and the solvent removed from the filtrate by means of distillation under reduced pressure, obtaining the remainder. The obtained residue was subjected to purification using kolonochnoi, of methylene chloride and methanol as eluent, getting to 0.63 g (yield 100%) of the named compound as a yellow amorphous substance.

Rf = 0,17 (10:1 = methylene chloride:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/z 443 (M++H).

[]2D5+ 30,6o(C = 0,32, CHCl3).

Spectrum of infrared absorptionmaxmax(cm-1): 1743, 1660.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,97 (1H, doublet, J = 2.3 Hz);

the 5.51 (1H, broad doublet, J = 9.0 Hz);

5,43 (1H, doublet of doublets, J = 5.0 and 1.9 Hz);

however, 4.40 (1H, doublet of doublets, J = 17,2 and 6.5 Hz);

4,37 (1H, doublet of doublets, J = 9.9 and 1,4 Hz);

to 4.15 (1H, doublet of doublets, J = 8,9 and 6.3 Hz);

of 3.95 (1H, doublet of doublets, J = 8.7 and 6.8 Hz);

of 3.80 (3H, singlet);

to 3.73 - of 3.80 (1H, multiplet);

of 3.60 (1H, doublet of doublets, J = 19,0 and 9.3 Hz);

2,24 - 2,49 (2H, multiplet);

2,02 (3H, singlet);

1,53 is 1.70 (2H, multiplet);

of 1.37 (3H, singlet);

of 1.35 (3H, singlet);

1,25 - of 1.43 (4H, multiplet);

0,86 - of 0.94 (3H, multiplet).

1 (v) 5-Acetamido-4-amino-7-O-hexanoyl-8,9-O-isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - enternotify acid

470 mg (1.06 mmol) of methyl 5-acetamido-4-amino-7 hexanoyl-8, 9 isopropylidene-2,3,4,5-terml of methanol and 4 ml of water, to the resulting solution was added with stirring at room temperature 47 mg (1.12 mmol) of lithium hydroxide 1 hydrate. The mixture is then stirred for an additional 30 minutes. At the end of this time the mixture gradually add Dowex-50Wx8 (H+) resin (Dowex is a trademark), the pH of the mixture is brought to a value of about 7.5. Immediately after adjusting the pH of the resulting suspension is rapidly filtered under reduced pressure. The residue obtained by distillation of the filtrate under reduced pressure was subjected to purification using column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 375 mg (yield 82%) of the named compound as a colourless solid.

Rf = 0,26 (2:5:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/z 429 (M++H).

[]2D5= +8,3o(C = 0,48, CH3)OH.

Spectrum of infrared absorptionmaxmax(cm-1): 1750, 1666.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

the ceiling of 5.60 (1H, doublet, J = 2.1 Hz);

5,41 (1H, doublet of doublets, J = 5.4 and 1.9 Hz);

4,58 (1H, triplet, J = 6.0 Hz);

4,15 - to 4.28 (3H, multiplet);

3,9

1,53 is 1.70 (2H, multiplet);

of 2.35 (3H, singlet);

of 1.32 (3H, singlet);

1,25 - of 1.43 (4H, multiplet);

0,87 - to 0.96 (3H, multiplet).

1 (vi) 5-Acetamido-4-amino-7-O-hexanoyl-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

270 mg (0,63 mmol) of 5-acetamido-4-amino-7-hexanoyl-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (v) above] dissolved in a mixture of 12 ml of acetic acid and 3 ml of water at room temperature, and the mixture is then stirred at 60oC for 2.5 hours. At the end of this time the residue obtained by distillation of the solvent under reduced pressure, subjected to azeotropic distillation with benzene and then concentrated to dryness in vacuo. The resulting residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 174 mg (71% yield) of the named compound as a colourless solid.

Rf = 0,32 (5:1:1 = isopropanol : ethyl acetate : methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/z 389 (M++H).

[]2D5= +1,1o(C = 0,14, CH3OH).

Spectrum of infrared absorptioniahc) (ppm):

to 5.66 (1H, doublet, J = 2.2 Hz);

to 5.13 (1H, doublet of doublets, J = 9,3 and 1.7 Hz);

4,47 (1H, doublet of doublets, J = 10.5 and 1.3 Hz);

to 4.17 (1H, triplet, J = 10.0 Hz);

4,00 - 4,10 (2H, multiplet);

3,59 (1H, doublet of doublets, J = 12,0 and 3.1 Hz);

3,39 (1H, doublet of doublets, J = 12,0 and 6.1 Hz);

2,32 - 2,39 (2H, multiplet);

at 1.91 (3H, singlet);

1,45 - to 1.63 (2H, multiplet);

1,20 of 1.28 (4H, multiplet);

0,78 is 0.86 (3H, multiplet).

1 (vii) 5-Acetamido-4-cyanamide-7-O-hexanoyl-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

155 mg (0.40 mmol) of 5-acetamido-4-amino-7 hexanoyl - 2,3,4,5-tetradeoxy - D-glycero galacto-non-2-topiramate acid [obtained as described in stage (vi) above] dissolved in 4 ml of methanol, and to the resulting solution, with stirring and at room temperature, added 65 mg (0.80 mmol) of sodium acetate and 53 mg (0.50 mmol) of bromine cyan. Then the reaction mixture was stirred at room temperature for an additional 40 minutes, then remove the solvent by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, getting 144 mg (yield 85%) of these compounds in Spectr (the Belarusian library Association, FAB) m/z 436 (M++Na), 452 (M++To).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,73 (1H, doublet, J = 1.0 Hz);

5,07 (1H, doublet of doublets, J = 7.8 and 1.2 Hz);

of 4.49 (1H, doublet, J = a 10.6 Hz);

4,47 (1H, doublet of doublets, J = 10.5 and 1.3 Hz);

4,05 - 4,18 (2H, multiplet);

of 3.85 (1H, doublet of doublets, J = 9,8 and 1.8 Hz);

3,63 - to 3.73 (1H, multiplet);

3,48 - to 3.58 (1H, multiplet);

2,28 - 2,48 (2H, multiplet);

of 1.95 (3H, singlet);

1,54 by 1.68 (2H, multiplet);

1,28 - of 1.40 (4H, multiplet);

0,87 - to 0.96 (3H, multiplet).

1 (viii) 5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-7-O - hexanoyl-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - enternotify acid

88 mg (0.21 mmol) of 5-acetamido-4-cyanamide-7 hexanoyl-2,3,4,5-tetradeoxy-O - glycero galacto-non-2-topiramate acid [obtained as described in stage (vii) above] dissolved in 4 ml of methanol, and to the resulting solution under stirring at room temperature, is added 15 mg (0.21 mmol) of hydroxylamine hydrochloride. Then the reaction mixture was stirred at room temperature for 2.5 hours, then remove the solvent by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel using 2 the organisations in the form of a colorless solid.

Rf = 0.50 (a 5:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/z 447 (M++H).

[]2D5= +28,0o(C = 0,035, CH3OH).

Spectrum of infrared absorptionmaxmax(cm-1): 1727, 1661, 1631.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

to 5.57 (1H, doublet, J = 1.9 Hz);

to 5.13 (1H, doublet of doublets, J = 8.7 and 1.9 Hz);

4,47 (1H, broad doublet, J = 10,2 Hz);

the 4.29 (1H, broad doublet, J = 9,3 Hz);

is 4.21 (1H, triplet, J = 9.9 Hz);

EUR 4.00 - 4.09 to (1H, multiplet);

to 3.58 (1H, doublet of doublets, J = 8,7 and 3.4 Hz);

of 3.43 (1H, doublet of doublets, J = 11.5 and 5.7 Hz);

2,30 - to 2.40 (2H, multiplet);

at 1.91 (3H, singlet);

1,52 by 1.68 (2H, multiplet);

1,28 - of 1.40 (4H, multiplet);

from 0.88 to 0.96 (3H, multiplet).

EXAMPLE 2

5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid (Compound N 34-1)

< / BR>
2 (i) 5-Acetamido-4-(C-aminooxy-C-aminoethylamino)- 2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

20 mg (0.05 mmol) 5-acetamido-4 aminooxy aminoethylamino)-7 hexanoyl-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid (obtained as described in Example 1) Rast is 9 M methanolic solution of sodium methoxide (0.01 mmol). Then the solution was stirred at room temperature for another 2 hours, then add 4 M solution of hydrogen chloride in dioxane, to bring the pH to a value of 6 to 7. The mixture is then evaporated to dryness in a vacuum. The resulting residue is purified by using column chromatography on silica gel using 5:1:1 by volume mixture of isopropanol, ethyl acetate and water, getting to 7.3 mg (yield 50%) of the named compound as a colourless solid.

Rf = 0,30 (4:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 325 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

to 5.58 (1H, doublet, J = 2.0 Hz);

was 4.42 (1H, doublet of doublets, J = 10,0 and 2.0 Hz);

4,30 (1H, doublet, J = 10.0 Hz);

4,20 (1H, doublet of doublets, J = 10,0 and 10.0 Hz);

are 3.90 (1H, multiplet);

of 3.85 (1H, doublet of doublets, J = 12,0 and 2.2 Hz);

3,55 - the 3.65 (2H, multiplet);

to 1.99 (3H, singlet).

EXAMPLE 3

5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-9-O-hexanoyl-2,3,4, 5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid (Compound N 34-36)

< / BR>
3 (i) 5-Acetamido-4-amino-9-O-hexanoyl-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

80 mg (0.21 mmol) of 5-acetamido-4-amino-7 hexane is straut in a mixture of 3 ml triperoxonane acid and 6 ml of methylene chloride at room temperature, and then the mixture is stirred at room temperature for another 6 hours. At the end of this time the solvent is removed by distillation under reduced pressure, obtaining the remainder. This residue is subjected to azeotropic distillation with benzene, after which it is evaporated to dryness under vacuum. Then the obtained residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 55 mg (yield 68%) of the named compound as a colourless solid.

Rf = 0,39 (5:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 389 (M++H).

[]2D5+10,0o(C = 0,07, CH3OH).

Spectrum infrared absorptionmaxmax(cm-1): 1724, 1664.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

to 5.56 (1H, doublet, J = 2.1 Hz);

to 4.38 (1H, doublet of doublets, J = 11.1 and 1.9 Hz);

4,30 (1H, singlet);

to 4.28 (1H, doublet, J = 1.9 Hz);

4,07 - of 4.25 (2H, multiplet);

3,93 - was 4.02 (1H, multiplet);

to 3.58 (1H, doublet, J = 9,3 Hz);

is 2.37 (2H, triplet, J = 7.4 Hz);

2,04 (3H, singlet);

1,57 - 1,71 (2H, multiplet);

1,27 - of 1.40 (4H, multiplet);

from 0.88 to 0.96 (3H, multiplet) the I acid

46 mg (0.12 mmol) of 5-acetamido-4-amino-9 hexanoyl - 2,3,4,5-tetradeoxy glycero galacto-non-topiramato acid [obtained as described in stage (i) above] dissolved in 10 ml of methanol, and to the resulting solution under stirring at room temperature added 29 mg (0.35 mmol) of sodium acetate and 17 mg (0.16 mmol) of labraid. The reaction mixture was stirred at room temperature for a further 40 minutes and then the solvent is removed by distillation under reduced pressure, obtaining the remainder. This residue is subjected to column chromatography on silica gel using 2: 5: 12, by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 29 mg (yield 60%) of the named compound as a colourless solid.

Rf = 0,43 (2:5:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 436 (M++Na), 458 (M++2Na-H).

[]2D5+8,27o(C = 0.075, the CH3OH).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

to 5.66 (1H, doublet, J = 2.0 Hz);

3,95 is 4.36 (6H, multiplet);

to 3.67 (1H, doublet, J = 7,4 Hz);

of 2.36 (2H, triplet, J = 7.5 Hz);

is 2.05 (3H, singlet);

1,55 - 1,71 (2H, multiplet);

1,27 - of 1.40 (4H, multiplet);

from 0.88 to 0.96 (3H, multiplet-non-2-enternotify acid

24 mg (0.06 mmol) of 5-acetamido-4-cyanamide hexanoyl-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (ii) above] dissolved in 4 ml of methanol, and to the resulting solution under stirring at room temperature add 4.5 mg (0.06 mmol) of hydroxylamine hydrochloride. The reaction mixture was stirred at room temperature for additional 4 hours, then remove the solvent by distillation under reduced pressure, obtaining the remainder. This residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 18 mg (yield 70%) of the named compound as a colourless solid.

Rf = 0,58 (5:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 447 (M++H).

[]2D5+39,2o(C = 0,025, CH3OH).

Spectrum of infrared absorptionmaxmax(cm-1): 1723, 1656.

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

to 5.57 (1H, doublet, J = 2.0 Hz);

4,30 - to 4.46 (3H, multiplet);

4,08 - of 4.25 (3H, multiplet);

3,68 (1H, doublet, J = 9.4 Hz);

is 2.37 (2H, triplet, J = 7,3 CLASS="ptx2">

EXAMPLE 4

5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-7-O - deletion-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - enternotify acid (Compound N 106-1)

< / BR>
4 (i) of Methyl 5-acetamido-4-azido-7-O-deletion-8,9-O - isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - topiramate

1.50 g (of 4.05 mmol) of methyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate [obtained as described in Example 1 (ii)] was dissolved in 30 ml of methylene chloride, and to the obtained solution under stirring in a bath with ice add 545 mg (of 4.45 mmol) dimethylaminopyridine and of 1.32 ml (a 4.86 mmol) deletion of chloride. Then the reaction mixture was stirred at room temperature for 40 minutes, then to 0.62 ml (of 4.45 mmol) of triethylamine is added dropwise to the mixture in a bath with ice. The mixture is then stirred at room temperature for 20 hours. At the end of this time the reaction mixture is added 200 ml of ethyl acetate and 100 ml of a saturated aqueous solution of acid sodium carbonate, and the mixture is separated, to separate the organic layer. The organic layer is washed three times, each time with 50 ml of a saturated aqueous solution of sodium chloride. Then it is dried over anhydrous sulfate is Laut column chromatography on silica gel, using 100: 1, by volume mixture of methylene chloride and methanol as eluent, obtaining of 1.57 g (yield 67%) of the named compound as a yellow oil.

Rf = 0,49 (20:1 = methylene chloride:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 603 (M++Na).

[]2D5-56,4o(C = 0,11, CHCl3).

Spectrum of infrared absorptionmaxmax(cm-1): 2100, 1745, 1661.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

6,14 (1H, doublet, J = 5.8 Hz);

5,77 (1H, broad doublet, J = 9.8 Hz);

5,42 (1H, doublet of doublets, J = 5,2 and 2.1 Hz);

4,37 - a 4.53 (2H, multiplet);

4,10 - 4,27 (3H, multiplet);

of 3.94 (1H, doublet of doublets, J = 8,7 and 6.7 Hz);

a 3.83 (3H, singlet);

2,21 - 2,47 (2H, multiplet);

to 1.99 (3H, singlet);

1,52 by 1.68 (2H, multiplet);

of 1.37 (3H, singlet);

of 1.35 (3H, singlet);

of 1.20 to 1.48 (20H, multiplet);

of 0.85 to 0.92 (3H, multiplet).

4 (ii) of Methyl 5-acetamido-4-amino-7-O-deletion-8,9-O - isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - topiramate

1.50 g (to 2.65 mmol) of methyl 5-acetamido-4-azido-7 deletion-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 20 ml of meta is Then the atmosphere in the reaction system is replaced by hydrogen, and the mixture is stirred at room temperature for 2 hours. At the end of this time the reaction system was filtered under reduced pressure using a Celite (trade mark) auxiliary filtering material, and the solvent removed from the filtrate by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel using a 20:1 by volume mixture of methylene chloride and methanol and then 10:1, by volume mixture of methylene chloride and methanol as eluent, getting 710 mg (yield 50%) of the named compound as a yellow amorphous substance.

Rf = 0, 29 ( 10:1 = methylene chloride:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 555 (M++H).

[]2D5+25,2o(C = 0,25, CHCl3).

Spectrum of infrared absorptionmaxmax(cm-1): 1753, 1738, 1660.

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

5,98 (1H, doublet, J = 2,01 Hz);

5,61 (1H, broad singlet);

5,43 (1H, doublet of doublets, J = 5.1 and 1.9 Hz);

4,35 is 4.45 (2H, multiplet);

to 4.15 (1H, doublet of doublets, J = 8,9 and 6.3 Hz);

3,9.5 (1H, doublet of doublets, J = 8,9 and 6.8 Hz);

a 3.83 (1H, broad singlet);

of 3.80 (3H, singlet);

of 3.64 (1H, broad doublet, J is t);

of 1.37 (3H, singlet);

of 1.35 (3H, singlet);

1,22 - 1,35 (20H, multiplet);

of 0.85 to 0.92 (3H, multiplet).

4 (iii) 5-Acetamido-4-amino-7-O-deletion-8,9-O - isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto - non-2-enternotify acid

710 mg (1.28 mmol) of methyl 5-acetamido-4-amino-7 deletion-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (ii) above] dissolved in a mixture of 4 ml of methanol and 4 ml of water, and the resulting solution was added 59 mg (1,41 mmol) of lithium hydroxide 1 hydrate, under stirring at room temperature. The mixture is then stirred for an additional 30 minutes at room temperature. Then gradually add to the mixture Dowex-50Wx8 (H+) resin (Dowex is a trademark), the pH of the mixture is brought to a value of about 7.5. Immediately after adjusting the pH of the resulting suspension is rapidly filtered under reduced pressure. The residue obtained by distillation of the solvent from the filtrate under reduced pressure was subjected to purification using column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, getting 490 mg (71% yield) of the named compound as a colourless solid substances>/P>[]2D5+10,8o(C = 0,12, CH3OH),

Spectrum of infrared absorptionmaxmax(cm-1): 1750, 1666.

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

5,61 (1H, doublet, J = l,9 Hz);

5,41 (1H, doublet of doublets, J = 6,0 and 1.4 Hz);

4,59 (1H, doublet of doublets, J = 12,0 and 6.2 Hz);

4,13 - to 4.28 (3H, multiplet);

3,93 (1H, doublet of doublets, J = 9.0 and 6.4 Hz);

3,79 - 3,86 (1H, multiplet);

2,28 - to 2.42 (2H, multiplet);

a 1.96 (3H, singlet);

1,52 is 1.70 (2H, multiplet);

of 1.35 (3H, singlet);

of 1.33 (3H, singlet);

1,26 - 1,43 (20H, multiplet);

0,87 - of 0.95 (3H, multiplet).

4 (iv) 5-Acetamido-4-amino-7-O-deletion-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

480 mg (0.89, mmol) 5-acetamido-4 - amino-7 deletion-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (iii) above] dissolved in a mixture of 10 ml acetic acid and 10 ml of water at room temperature, and the mixture is stirred for 5 hours at room temperature. Then the solvent is removed by distillation under reduced pressure and the resulting residue is subjected to azeotropic distillation with benzene, and then evaporated is using 2: 5:1, by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 110 mg (yield 25%) of the named compound as a colourless solid.

Rf = 0,37 (5:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 501 (M++H).

[]2D5+7,50o(C = 0,07, CH3OH).

Spectrum of infrared absorptionmaxmax(cm-1): 1740, 1661.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,59 (1H, doublet, J = 2.2 Hz);

5,14 (1H, doublet of doublets, J = 9,4 and 1.8 Hz);

was 4.42 (1H, doublet of doublets, J = 10.7 and 1.7 Hz);

to 4.23 (1H, triplet, J = 10.1 Hz);

to 4.01 - 4.09 to (1H, multiplet);

a 3.83 (1H, doublet of doublets, J = a 9.4 and 2.1 Hz);

of 3.56 (1H, doublet of doublets, J = 11.8 and a 3.2 Hz);

3,40 (1H, doublet of doublets, J = 11.7 and 6.3 Hz);

2,28 - of 2.38 (2H, multiplet);

of 1.95 (3H, singlet);

1,52 by 1.68 (2H, multiplet);

1,26 - 1,38 (20H, multiplet);

0,87 - of 0.95 (3H, multiplet).

4 (v) 5-Acetamido-4-cyanamide-7-O-deletion-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

108 mg (0.22 mmol) of 5-acetamido-4-amino-7 deletion-2,3,4,5-tetradeoxy glycero galacto-non-topiramato acid [obtained as described in stage (iv) above] rest the thief, under stirring at room temperature. The reaction solution was stirred at room temperature for 150 minutes and then the solvent is removed by distillation under reduced pressure, obtaining the remainder. The residue is then subjected to azeotropic distillation with benzene. The resulting residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 66 mg (yield 58%) of the named compound as a colourless solid.

Rf = 0,30 (2:5:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 526 (M++H).

[]2D5-36,3o(C = 0,07, CH3OH).

Spectrum of infrared absorptionmaxmax(cm-1): 2223, 1746, 1662.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,71 (1H, doublet, J = 2.1 Hz);

to 5.08 (1H, doublet of doublets, J = 8,2 and 1.8 Hz);

to 4.46 (1H, doublet of doublets, J = 10.6 and 1.7 Hz);

Android 4.04 - 4,20 (2H, multiplet);

of 3.85 (1H, doublet of doublets, J = 9.5 and 2.2 Hz);

3,66 (1H, doublet of doublets, J = 11.5 and 3.5 Hz);

3,45 - of 3.54 (1H, multiplet);

2,25 - 2,50 (2H, multiplet);

a 1.96 (3H, singlet);

1,53 by 1.68 (2H, multiplet);

1,26 - of 1.40 (20H is emanoil-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - enternotify acid

51 mg (0.1 mmol) of 5-acetamido-4-cyanamide-7 deletion-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (v) above] dissolved in 4 ml of methanol, and 7.6 mg (0.1 mmol) of hydroxylamine hydrochloride is added to the resulting solution, with stirring at room temperature. The reaction solution was stirred at room temperature for additional 3 hours after which the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 34 mg (yield 63%) of the named compound as a colourless solid.

Rf = 0,37 (5:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 559 (M++H).

[]2D5+22,5o(C = 0,065, CH3OH).

Spectrum of infrared absorptionmaxmax(cm-1): 1743, 1726, 1664, 1633.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 5.55 (1H, doublet, J = 1.9 Hz);

5,12 (1H, doublet of doublets, J = 9.2 and 2.0 Hz);

of 4.44 (1H, doublet of doublets, J = 10.2 and 1.5 Hz);

4,17 - to 4.33 (2H, multiplet);
2,28 - to 2.42 (2H, multiplet);

at 1.91 (3H, singlet);

1,53 is 1.70 (2H, multiplet);

1,26 - 1,39 (20H, multiplet);

0,87 - of 0.94 (3H, multiplet).

EXAMPLE 5

5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-9-O - deletion-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - enternotify acid (Compound N 34-41)

< / BR>
5 (i) 5-Acetamido-4-amino-9-O-deletion-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

55 mg (1.01 mmol) of 5-acetamido-4-amino-7 deletion-8,9 isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in Example 4 (iii)] dissolved in a mixture of 2 ml triperoxonane acid and 4 ml of methylene chloride at room temperature, and the mixture is then stirred at room temperature for a further 3 days. At the end of this time the solvent is removed by distillation under reduced pressure, obtaining the remainder. This residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 51 mg (yield 100%) of the titled compound as colorless solids

Rf = 0,49 (5:1:1 = isopropanol:ethyl acetate:methanol).

Mass spectrum (of the Belarusian library Association, FAB) m/e 501 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 5.68 (1H, doublet, J = 1.9 Hz);

4,01 - to 4.38 (3H, multiplet);

3,84 - 4,00 (4H, multiplet);

3,71 (1H, doublet, J = 7,7 Hz);

2,30 - to 2.42 (2H, multiplet);

to 2.06 (3H, singlet);

1,53 - 1,71 (2H, multiplet);

1,26 - of 1.40 (20H, multiplet);

0,87 with 0.93 (3H, multiplet).

5 (ii) 5-Acetamido-4-cyanamide-9-O-deletion-2,3,4,5-tetradeoxy-D-glycero - D-galacto-non-2-enternotify acid

90 mg (0.18 mmol) of 5-acetamido-4-amino-9 deletion-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (i) above] dissolved in 10 ml of methanol, and 44 mg (0.54 mmol) of sodium acetate and 19 mg (0.18 mmol) of labraid added to the obtained solution under stirring at room temperature. Then the reaction mixture was stirred at room temperature for 10 hours, after which the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 75 mg (yield 79%) of the named compound as a colourless solid CLASS="ptx2">

[]2D5-56,7o(=to 0.060, CH3OH).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

5,70 (1H, doublet, J = 1.9 Hz);

4,05 - 4,32 (3H, multiplet);

3,78 - was 4.02 (4H, multiplet);

2,32 - of 2.38 (2H, multiplet);

to 2.06 (3H, singlet);

1,55 by 1.68 (2H, multiplet);

1,26 - of 1.40 (20H, multiplet);

0,87 with 0.93 (3H, multiplet).

5 (iii) 5-Acetamido-4-(C-aminooxy-C-aminoethylamino)-9-O-deletion - 2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

55 mg (0.11 mmol) of 5-acetamido-4-cyanamide-9 deletion-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (ii) above] dissolved in 4 ml of methanol, and 27 mg (0,39 mmol) of hydroxylamine hydrochloride is added to the resulting solution, with stirring at room temperature. Then the reaction mixture was stirred at room temperature for a further 2 hours after which the solvent is removed by distillation under reduced pressure. The resulting residue is subjected to column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 11 mg (yield 19%) of the named compound as a colourless Tom++H).

[]2D5+53,3o(C = 0,015, CH3OH).

Spectrum of infrared absorptionmaxmax(cm-1): 1679.

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 5.53 (1H, doublet, J = 1.9 Hz);

4,30 - 4,43 (2H, multiplet);

a 4.03 - to 4.28 (3H, multiplet);

3,55 - the 3.65 (2H, multiplet);

2,32 - to 2.40 (2H, multiplet);

a 2.00 (3H, singlet);

1,55 by 1.68 (2H, multiplet);

of 1.26 to 1.37 (20H, multiplet);

0,85 with 0.93 (3H, multiplet).

EXAMPLE 6

Salt triperoxonane acid, 5-Acetamido-4-guanidino-2,3,4,5,7 - pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound N 1-1)

< / BR>
6 (i), Methyl 5-acetamido-4-azido-8,9-di-O-acetyl-2,3,4,5,7 - pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

300 mg (0.70 mmol) of methyl 5-acetamido-4,8,9-tri acetyl-2,6-anhydrous-3,5,7-trideoxy-7 - fluorescent glycero galacto-non-2-topiramate [obtained according to the method described in WO 95/32955] dissolved in 10 ml of anhydrous methylene chloride, and the resulting solution was added 25 mg (0.78 mmol) of methanol. The atmosphere in the reaction system is replaced by nitrogen, and then the reaction system is added 1.0 g (7.0 mmol) complex salt, boron TRIFLUORIDE-diethyl ether, and the mixture is up in a mixture of 50 ml of water, 10 g of ice, 10 g of solid acid sodium carbonate and 50 ml of ethyl acetate, and the mixture is vigorously stirred for 10 minutes. The organic layer is separated, washed with 10 ml saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The obtained residue (210 mg) was dissolved in 4 ml of dimethylformamide, and the resulting solution was added 400 g of a cation exchange resin, Dowex-50x8 (H+) (Dowex is a trademark) and 100 mg (1.53 mmol) of sodium azide. The mixture was then stirred at 80oC for 4 hours. At the end of this time Dowex-50x8 (H+) is separated by filtration and the solvent is removed by distillation under reduced pressure. Then, to dissolve the residue, add 30 ml of ethyl acetate and 20 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified by column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 170 mg (yield 59%) named the D5+69,4o(C = 0,18, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 417(M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

2,07 (9H, singlet);

to 3.58 (1H, double doublet of doublets, J = 9,0, 9.0 and 9.0 Hz);

of 3.80 (3H, singlet);

4,22 (1H, double doublet of doublets, J = 1,8, 5,2 and 13.0 Hz);

the 4.65 - 5,00 (4H, multiplet);

the 5.45 (1H, multiplet);

5,98 (1H, doublet, J = 2,8 Hz);

6,00 (1H, doublet, J = 8.5 Hz).

6 (ii) of Methyl 5-acetamido-4-(N,N'-bis-t-butoxycarbonylamino)-8,9-di-O-acetyl-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate

36 mg (0.08 mmol) of methyl 5-acetamido-4-azido - 8,9-di acetyl-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of methanol, and the resulting solution was added 10 mg of Lindlar catalyst. The atmosphere in the reaction system is replaced by hydrogen, and the mixture is then stirred for 2 hours. Then the catalyst is separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 2 ml of dimethylformamide, and the resulting solution was added 26 mg (0,093 mmol) N, N'-di-t-butoxycarbonylamino, 19 mg (0,186 mmol) of triethylamine and 25 mg (0,093 about is separated by filtration and the filtrate is poured into 2-layer mixture of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using a 2: 1 by volume mixture of ethyl acetate and hexane as eluent, receiving 32 mg (yield 59%) of the named compound as a colorless amorphous substance

Rf = 0.35 in (2:1 = ethyl acetate:hexane).

[]2D5+5,6o(C = 0,16, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 633 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

for 1.49 (9H, singlet);

of 1.52 (9H, singlet);

to 1.98 (3H, singlet);

is 2.05 (3H, singlet);

2,07 (3H, singlet);

of 3.80 (3H, singlet);

4,00 - 4,30 (3H, multiplet);

of 4.75 (1H, doublet of doublets, J = 9,2, 50 Hz);

4,78 (1H, doublet, J = 18 Hz);

5,23 (1H, doublet of doublets, J = 9,0, 9.0 Hz);

5,43 (1H, multiplet);

5,88 (1H, doublet, J = 2,8 Hz);

to 6.80 (1H, doublet, J = 8,2 Hz);

at 8.60 (1H, doublet, J = 8.5 Hz).

6 (iii) Salt triperoxonane acid, 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid

32 mg (0.05 mmol) of methyl 5-acetamido-4 - bis-t-the military, as described in stage (ii) above] dissolved in 2 ml of methanol, and the resulting solution was added 0.5 ml O 1 N methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the mixture is neutralized 4M solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. Then the residue is dissolved in 3:1, by volume mixture of methylene chloride-triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure and the resulting residue is dissolved in 1 ml of distilled water, and then to the resulting solution was added 70 ml of 1 N aqueous sodium hydroxide solution. The mixture is then stirred at room temperature for 1 hour. Dowex - 50x8(H+) (Dowex is a trademark) is added to the mixture to neutralize it, and then water is removed by distillation. The resulting residue is purified by column chromatography on silica gel using 5:1:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 16 mg (71% yield) of the named compound as a colourless solid.

Rf = CLASS="ptx2">

Mass spectrum (of the Belarusian library Association, FAB) m/e 335 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

a 2.00 (3H, singlet);

the 3.65 (1H, double doublet of doublets, J = 2,4, and 5.5 and 12.0 Hz);

of 3.85 (1H, double doublet of doublets, J = 2,5, 2,5 and 12 Hz);

to 4.15 (1H, multiplet);

to 4.23 (1H, doublet, J = 9.0 Hz);

4,30 - 4,60 (3H, multiplet);

5,63 (1H, singlet).

EXAMPLE 7

Salt triperoxonane acid tetradecyl 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate (Compound 1-5 N)

< / BR>
7 (i) of Methyl 5-acetamido-4-azido-8,9-O-isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate

300 mg (to 0.72 mmol) of methyl 5-acetamido-4-azido-8,9-di acetyl-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non - 2-topiramate [obtained as described in Example 6 (i)] dissolved in 5 ml of methanol, and the resulting solution was added 0.2 ml of 1M methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture is neutralized 4M solution of hydrogen chloride in dioxane, and then the solvent is removed by distillation under reduced pressure. The residue is dissolved in 5 ml of acetone, and to the resulting esteemest at room temperature for 3 hours. The solid is separated by filtration and the solvent removed from the filtrate by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 140 mg (yield 52%) of the named compound as a colorless amorphous substance.

Rf = 0,33 (20:1 = methylene chloride:methanol).

[]2D5+111o(C = 0,13, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 373 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.37 (3H, singlet);

of 1.42 (3H, singlet);

is 2.05 (3H, singlet);

3,50 (1H, double doublet of doublets, J = 7,5, 7.5 and 9.5 Hz);

of 3.80 (3H, singlet);

of 4.13 (1H, double doublet of doublets, J = 1,2, of 6.0 and 9.0 Hz);

4,20 (1H, double doublet of doublets, J = 1,2, of 6.0 and 9.0 Hz);

of 4.45 (1H, multiplet);

4,70 (1H, double doublet of doublets, J = 1,5, 5,7 and 47.0 Hz);

the 4.90 (1H, doublet of doublets, J = 2.8 and 9.5 Hz);

to 4.92 (1H, double doublet of doublets, J = 1,0, 11,0 and 28.0 Hz);

5,90 (1H, doublet, J = 7,3 Hz);

5,96 (1H, doublet, J = 2,8 Hz).

7 (ii) Tetradecyl 5-acetamido-4-azido-8,9-O-isopropylidene - 2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

113 mg (0.31 mmol) of methyl 5, as described in stage (i) above] dissolved in 4 ml of 6:1 by volume mixture of methanol and water, and the resulting solution was added 0.33 ml of 1 M aqueous solution of potassium hydroxide. The mixture is then stirred at room temperature for 2 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is dried over anhydrous sodium sulfate at room temperature and under reduced pressure for 2 hours, obtaining a pale yellow solid. The solid is dissolved in 8 ml of acetonitrile, and the resulting solution was added 80 mg (0.3 mmol) of 18-crown-6 and 415 mg (1.5 mmol) of tetradecyl bromide. The mixture is then stirred at 80oC for 2 hours. At the end of this time the reaction mixture was poured into a 2-layer solution of 15 ml of ethyl acetate and 10 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 110 mg (yield 64%) Nazvanov is SUP>2
D5+52,9o(C = 0,09, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 555 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 0.80 - 0.95 (3H, singlet);

1,20 - 1,50 (24H, multiplet);

of 1.37 (3H, singlet);

of 1.42 (3H, singlet);

1,60 - 1,80 (2H, multiplet);

is 2.05 (3H, singlet);

4,10 - 4,30 (2H, multiplet);

of 4.45 (1H, multiplet);

4,72 (1H, double doublet of doublets, J = 1,5, 5,3 and 38.0 Hz);

the 4.90 (1H, doublet of doublets, J = 2.4 and 9.3 Hz);

to 4.92 (1H, double doublet of doublets, J = 1,0, 10,0 and 28.0 Hz);

5,97 (1H, doublet, J = 6.5 Hz);

5,95 (1H, doublet, J = 2,4 Hz).

7 (iii) Tetradecyl 5-acetamido-4-(N, N'-bis-t-butoxycarbonylamino)-8,9-O-isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate

110 mg (0.20 mmol) of tetradecyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (ii) above] dissolved in 5 ml of methanol, and the resulting solution was added 30 mg of Lindlar catalyst. The atmosphere in the reaction system is replaced by hydrogen. The mixture was then stirred for 2 hours. At the end of this time the catalyst was separated by filtration and the solvent is removed by distillation at penitent-butoxycarbonylmethylene, 35 mg (0,342 mmol) of triethylamine and 47 mg (0,17 mmol) of mercury chloride (II). The mixture is then stirred at room temperature for 1 hour. The solid is separated by filtration and the filtrate is poured into 2-layer solution of 15 ml of ethyl acetate and 10 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using a 2:1 by volume mixture of ethyl acetate and hexane as eluent, receiving 98 mg (yield 63%) of the named compound as a colorless viscous substance.

Rf = 0,30 (20:1 = methylene chloride:methanol).

[]2D5+2,2o(C = 0,14, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 771, (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 0.80 - 0.95 (3H, singlet);

1,20 - 1,40 (24H, multiplet);

of 1.36 (3H, singlet);

of 1.41 (3H, singlet);

for 1.49 (9H, singlet);

of 1.50 (9H, singlet);

1,60 - 1,80 (2H, multiplet);

is 2.05 (3H, singlet);

4,10 - 4,70 (6H, multiplet);

5,20 (1H, double doublet of doublets, J = 2,4, 7,5 triperoxonane acid tetradecyl 5-acetamido-4 - guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate

80 mg (0.11 mmol) of tetradecyl 5-acetamido-4 bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (iii) above] dissolved in 3:1, by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred for 4 hours at room temperature. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue purified by column chromatography on silica gel using 2: 8:1, by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 40 mg (yield 56%) of the named compound as a colourless solid.

Rf = 0.35 in (5:1:1 = t-butanol:acetic acid:water).

[]2D5+22,4o(C = 0,13, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/e 531 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

0,70 - 0,85 (3H, singlet);

1,10 - 1,30 (24H, multiplet);

1,50 - 1,80 (2H, multiplet);

a 2.00 (3H, singlet);

3,60 - of 3.80 (2H, multiplet);

4,10 - 4,30 (3H, multiplet);

4,40 - 4,60 (2H, multiplet);

5,88 (1H, singlet).

EXAMPLE 8

Salt triperoxonane acid 4-guanidino-5-thioacetamide is atamido-4-(N, N'-bis-t - butoxycarbonylamino)-7,8,9-tri-O-acetyl-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate

2.0 g (4,63 mmol) of 5-acetamido-4-amino-7,8,9-tri acetyl-2,3,4,5-tetradeoxy glycero galacto-non-2 - topiramate dissolved in 40 ml of dimethylformamide, and the resulting solution was added 1.54 g (5,58 mmol) bis-t - butoxycarbonylamino, 1.1 g in (11.2 mmol) of triethylamine and 1.54 g (5,58 mmol) of mercury chloride (II). The mixture is then stirred at room temperature for 2 hours. The insoluble matter is separated by filtration and the filtrate is poured into 2-layer solution of 50 ml of ethyl acetate and 25 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified by column chromatography on silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as eluent, obtaining 3.0 g (yield 96%) of the named compound as a colorless amorphous substance.

Rf = 0,20 (1:1 = ethyl acetate:hexane).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

for 1.49 (18H, R> to 4.15 (1H, doublet of doublets, J = 8,0 and 13.0 Hz);

4,20 - 4,30 (2H, multiplet);

of 4.67 (1H, doublet of doublets, J = 3,0 and 13.0 Hz);

further 5.15 (1H, double doublet of doublets, J = 2.5 and 8.5 and 8.5 Hz);

and 5.30 (1H, multiplet);

5,43 (1H, doublet of doublets, J = 2.5 and 5.3 Hz);

5,90 (1H, doublet, J = 2.5 Hz);

of 6.20 (1H, doublet, J = 8,2 Hz);

and 8.50 (1H, doublet, J = 8.5 Hz).

8 (ii) of Methyl 4-(N,N'-bis-t-butoxycarbonylamino)-5 - diacetamido-7,8,9-tri-O-acetyl-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate

1,95 g (2.89 mmol) of methyl 5-acetamido-4 - bis-t - butoxycarbonylamino)-7,8,9-tri acetyl-2,3,4,5 - tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 40 ml of tetrahydrofuran, and the resulting solution was added 2.15 g (5,32 mmol) Lawesson''s reagent. The mixture is then stirred at 60oC for 2 hours. Then the reaction mixture was poured in a 2-layer solution of 50 ml of ethyl acetate and 30 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified by column chromatography on silica gel, ispoll the form of a colorless amorphous substance.

Rf = 0.40 in (1:1 = ethyl acetate:hexane).

[]2D5+19,0o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 689 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.46 (9H, singlet);

for 1.49 (9H, singlet);

of 1.95 (3H, singlet);

of 1.97 (3H, singlet);

to 1.99 (3H, singlet);

to 2.42 (3H, singlet);

of 3.80 (3H, singlet);

to 4.15 (1H, doublet of doublets, J = 8,0 and 13.0 Hz);

of 4.45 (1H, doublet of doublets, J = 3.0 and 8.5 Hz);

4,70 (1H, doublet of doublets, J = 3,0 and 13.0 Hz);

5,20 to 5.35 (3H, multiplet);

of 5.40 (1H, doublet of doublets, J = 2.5 and 4.5 Hz);

of 5.92 (1H, doublet, J = 2.5 Hz);

of 7.95 (1H, doublet, J = 8,2 Hz);

8,55 (1H, doublet, J = 8.5 Hz);

8 (iii) Salt triperoxonane acid 4-guanidino-5-diacetamido - 2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate acid

800 mg (1,16 mmol) of methyl 4 - bis-t - butoxycarbonylamino)-5-diacetamido-7,8,9-tri acetyl-2,3,4,5 - tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (ii) above] dissolved in 10 ml of methanol, and the resulting solution was added 1.5 ml of 0.1 N methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 2 hours, after which it was neutralized with 4 M NaCl, bodoro is 0 ml of 3:1, by volume mixture of methylene chloride and triperoxonane acid, and the resulting solution was stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure and the resulting residue is dissolved in 10 ml of distilled water, and then to the resulting solution add 2.0 ml IN an aqueous solution of sodium hydroxide. The mixture is then stirred at room temperature for 1 hour. Dowex-h (H+) (Dowex is a trademark) is then added to neutralize the reaction mixture, and water is removed by distillation under reduced pressure. The resulting residue is purified by column chromatography on silica gel using 5:1:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, getting 215 mg (yield 40%) of the named compound as a colourless solid.

Rf = 0,30 (4:1:1 = isopropanol:ethyl acetate:water).

[]2D5+41,0o(C = 0,11, H2O).

Mass spectrum (of the Belarusian library Association, FAB) m/e 349 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

of 2.51 (3H, singlet);

3,55 (1H, doublet, J = 10 Hz);

3,62 (1H, doublet of doublets, J = 7,0 and 14.0 Hz);

of 3.85 (1H, doublet do blet, J = 2,5 Hz).

EXAMPLE 9

Salt triperoxonane acid hexyl 5-diacetamido-4-guanidino - 2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate (Compound N 31-3)

< / BR>
9 (i) of Methyl 5-diacetamido-4-(N,N'-bis-t - butoxycarbonylamino)-8,9-O-isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate.

700 mg (1.01 mmol) of methyl 4 bis-t-butoxycarbonylamino)-5-diacetamido-7,8,9-tri acetyl-2,3,4,5 - tetradeoxy glycero galacto-non-2-topiramate [obtained as described in Example 8 (ii)] was dissolved in 20 ml of methanol, and the resulting solution was added 0.2 ml of 1M methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture is neutralized 4M solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 30 ml of acetone, and the resulting solution was added 1.0 g (9,71 mmol) of 2,2 - dimethoxypropane and 40 mg (0.22 mmol) of p-toluensulfonate acid. The mixture is then stirred at room temperature for 3 hours. Then to the mixture was added 100 mg of solid acidic sodium carbonate, and the mixture is stirred for 30 minutes. Then twee. The resulting residue is purified by column chromatography on silica gel using 50:1, by volume, mixture meta - langarica and methanol as eluent, receiving 450 mg (yield 74%) of the named compound as a colorless amorphous substance.

Rf = 0,33 (20:1 = methylene chloride:methanol).

[]2D5+14,4o(C = 0,18, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 603 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.37 (3H, singlet);

of 1.41 (3H, singlet);

to 1.48 (9H, singlet);

is 1.51 (9H, singlet);

to 2.55 (3H, singlet);

3,50 (1H, doublet of doublets, J = 4.8 and 8.5 Hz);

of 3.80 (3H, singlet);

of 4.05 (1H, doublet of doublets, J = 5.0 and 9.0 Hz); 4,13 (1H, doublet of doublets, J = 7,3 and 9.2 Hz); 4,20 (1H, doublet, J = 10.0 Hz);

however, 4.40 (1H, multiplet);

4,55 (1H, double doublet of doublets, J = 7,4, of 10.0 and 10.0 Hz);

and 5.30 (1H, double doublet of doublets, J = 2,4, of 8.0 and 10.0 Hz);

of 5.84 (1H, doublet, J = 2,8 Hz);

8,68 (1H, J = 8.0 Hz);

9,04 (1H, J = 7,2 Hz).

9 (ii) of Hexyl 5-diacetamido-4-(N,N'-bis-t-butoxycarbonylamino)-8,9-O-isopropylidene-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - topiramate

190 mg (0.31 mmol) of methyl 5-diacetamido-4 bis-t - butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5-tetradeoxy gsmes of methanol and water, to the resulting solution was added of 0.32 ml of a 1M aqueous solution of potassium hydroxide. The mixture is then stirred at room temperature for 3 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is dried under reduced pressure at room temperature for 2 hours, obtaining a pale yellow solid. The solid is dissolved in 8 ml of acetonitrile, and the resulting solution was added 76 mg (0.29 mmol) of 18-crown-6 and 236 mg (1,43 mmol) of hexyl bromide. The mixture is then stirred at 80oC for 2 hours, after which it was poured into a 2-layer solution of 30 ml of ethyl acetate and 20 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using 3:1 by volume mixture of ethyl acetate and hexane as eluent, receiving 73 mg (yield 35%) of the named compound as a colorless amorphous substance.

Rf = 0,57 (20:1 = methylene chloride:methanol).

[]2D5+19,2o(C = 0,12, CHClthe NSA (CDCl3, 270 MHz) (ppm):

0,85 - 0,95 (3H, singlet);

1,20 - 1,50 (8H, multiplet);

of 1.36 (3H, singlet);

of 1.41 (3H, singlet);

to 1.48 (9H, singlet);

is 1.51 (9H, singlet);

1,60 - 1,80 (2H, multiplet);

of 2.56 (3H, singlet);

to 3.52 (1H, doublet of doublets, J = 4.8 and 8.5 MHz);

4,00 - 4,30 (3H, multiplet);

however, 4.40 (1H, multiplet);

4,55 (1H, double doublet of doublets, J = 7,4, of 10.0 and 10.0 Hz);

and 5.30 (1H, double doublet of doublets, J = 2,2, of 8.0 and 10.0 Hz);

of 5.82 (1H, doublet, J = 2.2 Hz);

8,68 (1H, J = 8.0 Hz);

of 9.02 (1H, J = 7,2 Hz).

9 (iii) Salt triperoxonane acid hexyl 5-diacetamido-4 - guanidino-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate

100 mg (0.15 mmol) of hexyl 5-diacetamido-4 - bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5 - tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (ii) above] dissolved in 12 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 4 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue purified by column chromatography on silica gel using 15: 1:1, by volume, mixture of t-butanol, ethyl acetate and water as eluent, receiving 65 mg (yield 79%) named the LASS="ptx2">

[]2D5-1,9o(C = 0,11, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/e 433 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

0,70 - 0,85 (3H, singlet);

1,10 - 1,40 (8H, multiplet);

1,60 - 1,70 (2H, multiplet);

of 2.50 (3H, singlet);

3,51 (1H, doublet, J = 8.5 Hz);

of 3.80 (1H, doublet, J = 10.0 Hz);

4,20 (2H, multiplet);

4,40 - 4,70 (2H, multiplet);

5,10 (1H, multiplet);

5,98 (1H, broad singlet).

EXAMPLE 10

Salt triperoxonane acid tetradecyl 5-diacetamido-4-guanidino-2,3,4,5-tetradeoxy - D-glycero-D-galacto-non-2-topiramate (Compound N 31-5)

< / BR>
10 (i) Tetradecyl 5-diacetamido-4-(N,N'-bis-t - butoxycarbonylamino)-8,9-O-isopropylidene-2,3,4,5-tetradeoxy-D - glycero-D-galacto-non-2-topiramate

234 mg (0,39 mmol) of methyl 5-diacetamido-4 - bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2 - topiramate [obtained as described in Example 9 (i)] is dissolved in 12 ml of 6:1 by volume mixture of methanol and water, and the resulting solution was added of 0.43 ml of 1 M aqueous solution of potassium hydroxide. The mixture is then stirred at room temperature for 3 hours. At the end of this time the solvent UDA is within 2 hours, receiving a pale yellow solid. The solid is dissolved in 8 ml of acetonitrile and the resulting solution was added 103 mg (0,39 mmol) of 18-crown-6 and 593 mg (1.94 mmol) of tetradecyl bromide. The mixture is then stirred at 80oC for 2 hours. At the end of this time the reaction mixture was poured into a 2-layer solution of 30 ml of ethyl acetate and 20 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified by column chromatography on silica gel using 3:1 by volume mixture of ethyl acetate and hexane as eluent, receiving 100 mg (yield 33%) of the named compound as a colorless amorphous substance.

Rf = 0.45 in (2:1 = hexane:ethyl acetate).

[]2D5+18,2o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/e 785 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,85 - 0,95 (3H, singlet);

1,20 - 1,50 (24H, multiplet);

of 1.36 (3H, singlet);

of 1.40 (3H, singlet);

to 1.48 (9H, singlet);

is 1.51 (9H, singlet);


however, 4.40 (1H, multiplet);

4,55 (1H, double doublet of doublets, J = 7,4, of 10.0 and 10.0 Hz);

and 5.30 (1H, double doublet of doublets, J = 2,2, of 8.0 and 10.0 Hz);

of 5.82 (1H, doublet, J = 2.2 Hz);

8,66 (1H, J = 8.0 Hz);

of 9.00 (1H, J = 7,2 Hz).

10 (ii) Salt triperoxonane acid tetradecyl 5-diacetamido-4-guanidino-2,3,4,5-tetradeoxy-D-glycero-D - galacto-non-2-topiramate

90 mg (0.11 mmol) of tetradecyl 5-diacetamido-4 bis-t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved 12 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 4 hours. At the end of this time the solvent is removed by distillation under reduced pressure and the resulting residue purified by column chromatography on silica gel using 15:1:1, by volume, mixture of t-butanol, ethyl acetate and water as eluent, receiving 40 mg (yield 47%) of the named compound as a colourless solid.

Rf = 0,80 (5:1:1 = t-butanol:acetic acid:water).

[]2D5-1,4o(C = 0,15, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/e 545 (M++H).

1H-Spectrum/BR> 1,60 - 1,70 (2H, multiplet);

of 2.50 (3H, singlet);

3,60 - 3,90 (2H, multiplet);

to 4.15 (2H, multiplet);

4,40 - 4,70 (2H, multiplet);

5,10 (1H, multiplet);

5,90 (1H, broad singlet).

EXAMPLE 11

Salt triperoxonane acid 4-guanidino-9-O-hexanoyl-5 - diacetamido-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2 - topiramate (Compound N 31-36)

< / BR>
11 (i) of Methyl 5-diacetamido-4-(N,N'-bis-t - butoxycarbonylamino)-7-O-hexanoyl-8,9-O-isopropylidene-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-topiramate

500 mg (0.83 mmol) of methyl 5-diacetamido-4 - bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5 - tetradeoxy glycero galacto-non-2-topiramate [obtained as described in Example 9 (i)] is dissolved in 15 ml of methylene chloride, and the resulting solution was added 110 mg (of 0.91 mmol) dimethylaminopyridine and 122 mg (of 0.91 mmol) hexanoyl chloride. The mixture is then stirred at room temperature for 30 minutes. Then to the resulting mixture are added 92 mg (of 0.91 mmol) of triethylamine and the mixture is stirred for 15 minutes. At the end of this time the reaction mixture was poured into a 2-layer solution of 30 ml of ethyl acetate and 15 ml of a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, after which the Rast is as silica gel, using 50:1, by volume mixture of methylene chloride and methanol as eluent, getting 432 mg (yield 74%) of the named compound as a colourless solid.

Rf = 0,30 (20:1 = methylene chloride:methanol).

[]2D5-18,0o(C = 0,10, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 701 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,85 - 0,95 (3H, singlet);

1,20 - 1,70 (6H, multiplet);

of 1.35 (3H, singlet);

to 1.38 (3H, singlet);

of 1.47 (9H, singlet);

to 1.48 (9H, singlet);

2,20 - of 2.50 (2H, multiplet);

to 2.42 (3H, singlet);

of 3.80 (3H, singlet);

to 3.92 (1H, doublet of doublets, J = 6.6 and 8.5 Hz);

4,10 (1H, doublet of doublets, J = 6.2 and 8.5 Hz);

4,35 is 4.45 (2H, multiplet);

of 5.15 to 5.35 (2H, multiplet);

5,90 (1H, doublet, J = 2.0 Hz);

at 7.55 (1H, J = 10.0 Hz);

8,55 (1H, J = 9.5 Hz).

11 (ii) 4-(N,N'-Bis-t-butoxycarbonylamino)-7-O-hexanoyl-8,9-O-isopropylidene-5-diacetamido-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

89 mg (0.13 mmol) of methyl 5-diacetamido-4 - bis-t - butoxycarbonylamino)-7 hexanoyl-8,9-isopropylidene-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 6:1, at the same time, the mixture is stirred at room temperature for 3 hours. At the end of this time the reaction mixture is neutralized 4N solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using 2: 5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 48 mg (yield 64%) of the named compound as a colourless solid.

Rf = 0.67 and (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5-25,0o(C = 0,10, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 687 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, singlet);

1,20 - 1,70 (6H, multiplet);

of 1.32 (3H, singlet);

of 1.35 (3H, singlet);

of 1.45 (9H, singlet);

is 1.51 (9H, singlet);

2,20 - of 2.50 (2H, multiplet);

of 2.35 (3H, singlet);

3,40 (1H, multiplet);

4,20 (1H, doublet of doublets, J = 6.2 and 8.5 Hz);

however, 4.40 (1H, doublet of doublets, J = 1.5 and 10.0 Hz);

4,55 (1H, multiplet);

5,00 (1H, doublet of doublets, J = 10,0 and 10.0 Hz);

5,10 (1H, doublet of doublets, J = 2,1 and 10.0 Hz);

and 5.30 (1H, doublet of doublets, J = 2.0 and 5.5 Hz);

5,73 (1H, doublet, J = 2.1 Hz).

11 (iii) Salt triperoxonane acid 4-guanidino-9-O-hexanoyl-5-diacetamido-2,3,4,5-t is Idina)-7 hexanoyl-8,9 isopropylidene-5-diacetamido-2,3,4,5-tetradeoxy glycero galacto-non-2-topiramate acid [obtained, as described in stage (ii) above] dissolved in 12 ml of 2:6:1 by volume mixture of methylene chloride, triperoxonane acid and thiophenol, and the mixture is stirred at room temperature for 8 hours. At the end of this time the solvent is removed by distillation under reduced pressure and the resulting residue purified by column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 54 mg (yield 53%) of the named compound as a colourless solid.

Rf = 0,55 (5:1:1 = t-butanol:acetic acid:water).

[]2D5+2,3o(C = 0,10, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 447 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

0,70 - 0,85 (3H, singlet);

1,20 - 1,70 (6H, multiplet);

2,30 - of 2.50 (2H, multiplet);

2,52 (3H, singlet);

3,51 (1H, doublet, J = 8.5 Hz);

to 4.15 (1H, multiplet);

to 4.23 (1H, doublet of doublets, J = 5.5 and 12.0 Hz);

of 4.35 (1H, doublet of doublets, J = 2.5 and 12.0 Hz);

4,40 - 4,60 (2H, multiplet);

5,10 (1H, multiplet);

5,63 (1H, doublet, J = 2,4 Hz).

EXAMPLE 12

Salt triperoxonane acid 4-guanidino-9-O-deletion-5-diacetamido - 2,3,4,5-tetradecane)-7-O-deletion-8,9-O-isopropylidene-5-diacetamido-2,3,4,5 - tetradeoxy-D-glycero-D-galacto-non-2-topiramate

440 mg (0.73 mmol) of methyl 5-diacetamido-4 bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5 - tetradeoxy glycero galacto-non-topiramate [obtained as described in Example 9 (i)] is dissolved in 15 ml of methylene chloride, and the resulting solution was added 132 mg (1,08 mmol) dimethylaminopyridine and 247 mg (1.0 mmol) deletion of chloride. The mixture is then stirred at room temperature for 30 minutes, then added 109 mg (1,08 mmol) of triethylamine, and the mixture is stirred for 15 minutes. Then the reaction mixture was poured in a 2-layer solution of 30 ml of ethyl acetate and 15 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The residue is purified by column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 350 mg (yield 59%) of the named compound as a colorless amorphous substance.

Rf = 0.35 in (1:1 = ethyl acetate:hexane).

[]2D5-17,6o(C = 0,15, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 813 (M++H).

1,20 - 1,70 (22H, multiplet);

of 1.35 (3H, singlet);

to 1.38 (3H, singlet);

of 1.47 (9H, singlet);

for 1.49 (9H, singlet);

2,20 - of 2.50 (2H, multiplet);

to 2.42 (3H, singlet);

of 3.80 (3H, singlet);

to 3.92 (1H, doublet of doublets, J = 6.6 and 8.5 Hz);

4,10 (1H, doublet of doublets, J = 6.2 and 8.5 Hz);

4,35 is 4.45 (2H, multiplet);

of 5.15 to 5.35 (2H, multiplet);

5,90 (1H, doublet, J = 2.0 Hz);

at 7.55 (1H, J = 10.0 Hz);

8,55 (1H, J = 9.5 Hz).

12 (ii) 4-(N, N'-Bis-t-butoxycarbonylamino)-7-O - deletion-8,9-O-isopropylidene-5-diacetamido-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enternotify acid

320 mg (0,39 mmol) of methyl 4 - bis-t-butoxycarbonylamino)- 7 deletion-8,9 isopropylidene-5 - diacetamido-2,3,4,5-tetradeoxy glycero galacto-non-2 - topiramate [obtained as described in stage (i) above] dissolved in 7 ml of 6:1 by volume mixture of methanol and water, and the resulting solution was added 18 mg (0.41 mmol) of lithium hydroxide 1 hydrate. The mixture is then stirred at room temperature for 3 hours. At the end of this time the reaction mixture was neutralized with 4 N solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified by column chromatography on silica gel, the connection in the form of a colorless solid.

Rf = 0,30 (10:1 = methylene chloride:methanol).

[]2D5-25,0o(C = 0,12, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 799 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, singlet);

1,20 - 1,70 (22H, multiplet);

of 1.32 (3H, singlet);

of 1.35 (3H, singlet);

of 1.45 (9H, singlet);

of 1.50 (9H, singlet);

2,20 - of 2.50 (2H, multiplet);

of 2.35 (3H, singlet),

of 3.95 (1H, doublet of doublets, J = 6.2 and 8.5 Hz);

4,20 (1H, doublet of doublets, J = 6.2 and 8.5 Hz);

however, 4.40 (1H, doublet of doublets, J = 1.5 and 10.0 Hz);

4,55 (1H, multiplet);

5,00 (1H, doublet of doublets, J = 10,0 and 10.0 Hz);

5,10 (1H, doublet of doublets, J = 2,1 and 10.0 Hz);

and 5.30 (1H, doublet of doublets, J = 2.0 and 5.5 Hz);

5,73 (1H, doublet, J = 2.1 Hz).

12 (iii) Salt triperoxonane acid 4-guanidino-9-O-deletion-5-diacetamido-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-topiramate acid

220 mg (0.27 mmol) 4 - bis-t-butoxycarbonylamino)- 7 deletion-8,9 isopropylidene-5-diacetamido-2,3,4,5 - tetradeoxy glycero galacto-non-2-topiramate acid [obtained as described in stage (ii) above] dissolved in 12 ml of 2:6:1 by volume mixture of methylene chloride, triperoxonane acid and thiophenol, and the mixture is stirred at room is the t and the resulting residue is purified column chromatography on silica gel, using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 120 mg (yield 56%) of the named compound as a colourless solid.

Rf = 0,60 (5:1:1 = t-butanol:acetic acid:water).

[]2D5+2,2o(C = 0,10, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 559 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

0,70 - 0,85 (3H, singlet);

1,20 - 1,70 (22H, multiplet);

2,30 - of 2.50 (2H, multiplet);

of 2.54 (3H, singlet);

3,61 (1H, doublet, J = 8.5 Hz);

to 4.15 (1H, multiplet);

4,20 (1H, doublet of doublets, J = 5.5 and 12.0 Hz);

4,30 (1H, doublet of doublets, J = 2.5 and 12.0 Hz);

4,40 - 4,60 (2H, multiplet);

5,10 (1H, multiplet);

the ceiling of 5.60 (1H, broad singlet).

EXAMPLE 13

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O - hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate acid (Compound 1-36 N)

< / BR>
13 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero - D-galacto-non-2-topiramate

100 mg (0.24 mmol) of methyl 5-acetamido-4 bis-t - butoxycarbonylamino)-8,9-di acetyl - 2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [the floor is nologo solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour, after which the reaction mixture was neutralized with 4 M solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 1 ml of distilled water and the resulting solution was added 280 ml of 1 N aqueous sodium hydroxide solution. The mixture is then stirred at room temperature for 1 hour, after which the reaction mixture was neutralized with 4 M solution of hydrogen chloride in dioxane and then water is removed by distillation. The resulting residue is dissolved in 3 ml of 6:1 by volume mixture of methanol and water, and the resulting solution was added 100 mg (0.52 mmol) diphenyldiazomethane and 8 mg (0.06 mmol) of the complex of boron TRIFLUORIDE-diethyl ether. The mixture is then stirred at room temperature for 2 hours. At the end of this time the reaction mixture with acetic acid, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 20:1 by volume mixture of methylene chloride and methanol as eluent, receiving 82 mg (yield 50%) of the named compound as a colorless amorphous substance.

R Mass spectrum (of the Belarusian library Association, FAB) m/z 701 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.50 (9H, singlet);

is 1.51 (9H, singlet);

of 1.95 (3H, singlet);

of 3.25 (2H, multiplet);

are 3.90 (2H, multiplet);

4,20 - 4,70 (3H, multiplet);

the 5.25 (1H, multiplet);

5,95 (1H, doublet, J = 2.5 Hz);

6,93 (1H, singlet);

7,10 (1H, doublet, J = 8.5 Hz);

7,20 - 7,40 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

13 (ii) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

50 mg (0,072 mmol) diphenylmethyl 5-acetamido-4 bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2 - topiramate [obtained as described in stage (i) above] dissolved in 2 ml of methylene chloride, and the resulting solution was added 11 mg (0.11 mmol) of triethylamine and 11 mg (0,086 mmol) hexanoyl chloride, while cooling with ice. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over betwedn column chromatography on silica gel, using 50: 1, by volume mixture of methylene chloride and methanol as eluent, receiving 47 mg (yield 83%) of the named compound as a colorless amorphous substance.

Rf = 0,6 (20:1 = methylene chloride:methanol).

[]2D5-4,0o(s = 0,1, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 786 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,20 - 1,40 (6H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.97 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

2,95 (1H, doublet, J = 5.0 Hz);

4,20 - 4,60 (6H, multiplet);

the 5.25 (1H, multiplet);

5,97 (1H, doublet, J = 2.6 Hz);

of 6.65 (1H, doublet, J = 8.5 Hz);

6,93 (1H, singlet);

7,20 - 7,40 (10H, multiplet);

at 8.60 (1H, doublet, J 8.5 Hz).

13 (iii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate acid

40 mg (0.05 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (ii) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture Paralela under reduced pressure, and the residue purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 18 mg (yield 65%) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5+60,0o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 433 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,25 - 1,40 (4H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 4.5 Hz);

4,10 - and 4.40 (5H, multiplet);

4,45 - 4,70 (2H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 2,4 Hz).

EXAMPLE 14

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O - octanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate acid (Compound N 1-38)

< / BR>
14 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-octanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

50 mg (0,072 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2 - topiramate [obtained as described in Example 13 (i)] rastvoryayas chloride, while cooling with ice. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 45 mg (yield 77%) of the named compound as a colorless amorphous substance.

Rf = 0,5 (20:1 = methylene chloride:methanol).

[]2D5-5,2o(C = 0,2, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 814 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.95 (3H, singlet);

the 3.65 (1H, doublet of doublets, J = 5.0 and 18 Hz);

of 3.80 (1H, doublet of doublets, J = 1.8 and 18 Hz);

to 4.15 (1H, multiplet);

to 4.23 (1H, doublet, J = 8.5 Hz);

4,30 - 4,60 (3H, multiplet);

5,95 (1H, doublet, J = 2.3 Hz).

14 (ii) Salt triperoxonane acid, 5-acetamido-4-the ol) diphenylmethyl 5-acetamido-4 - bis-t - butoxycarbonylamino)-9 octanoyl-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2 - topiramate [received, as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 18 mg (yield 64%) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5+56o(C = 0,2, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 461 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,25 - 1,40 (8H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 4.5 Hz);

4,10 - and 4.40 (5H, multiplet);

4,45 - 4,70 (2H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 2,4 Hz).

EXAMPLE 15

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadecane-D-fluorescent-D-glycero-D-galacto-non-2 - topiramate acid (Compound 1-40 N)

< / BR>
15 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonyl) diphenylmethyl 5-acetamido - 4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2-topiramate [received, as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and the resulting solution was added 10 mg (0.10 mmol) of triethylamine and 21 mg (0,094 mmol) dodecanoyl chloride, while cooling with ice. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as eluent, receiving 48 mg (yield 69%) of the named compound as a colorless amorphous substance.

Rf = 0,4 (1:1 = ethyl acetate:hexane).

[]2D5-5,7o(C = 0,12, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 883 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,20 - 1,40 (18H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.97 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

2,95 (1H, oak is, J = 8.5 Hz);

6,93 (1H, singlet);

7,20 - 7,40 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

15 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-0-dodecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate acid

43 mg (0.05 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 dodecanoyl-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 33 mg (yield 91%) of the named compound as a colourless solid.

Rf=0.4 (of 2:5:1=isopropanol: ethyl acetate: water).

[]2D5+22,7o(s = 0,1, CH3IT).

Mass spectrum (of the Belarusian library Association, FAB) m/z 517 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,25 - 1,40 (16H, multiplet);
4,45 - 4,70 (2H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 2,4 Hz).

EXAMPLE 16

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-deletion-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D - galacto-non-2-topiramate acid (Compound N 1-41)

< / BR>
16 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-deletion-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

50 mg (0,072 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent - glycero galacto-non-2-topiramate [obtained as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and the resulting solution was added 11 mg (0.11 mmol) of triethylamine and 21 mg (0,086 mmol) deletion of chloride, while cooling with ice. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silicagel connection in the form of a colorless amorphous substance.

Rf = 0,4 (1:1 = ethyl acetate:hexane).

[]2D5-7,0o(C = 0,10, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 898 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,20 - 1,40 (22H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.97 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

2,95 (1H, doublet, J = 5.0 Hz);

4,20 - 4,60 (6H, multiplet);

the 5.25 (1H, multiplet);

5,97 (1H, doublet, J = 2.6 Hz);

of 6.65 (1H, doublet, J = 8.5 Hz);

6,93 (1H, singlet);

7,20 - 7,40 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

16 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-deletion-2,3,4,5,7-pentadecane-7-fluorescent - D-glycero-D-galacto-non-2-topiramate acid

40 mg (0.05 mmol) diphenylmethyl 5-acetamido-4 - bis-t - butoxycarbonylamino)-9 deletion-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue purified colonocyte, getting 218 mg (yield 64%) of the named compound as a colourless solid.

Rf = 0.4 (of 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5+22,0o(C = 0,06, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 545 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,25 - 1,70 (20H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 4.5 Hz);

4,10 - and 4.40 (5H, multiplet);

4,45 - 4,70 (1H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 2,4 Hz).

EXAMPLE 17

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O - hexadecanoyl - 2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non - 2-topiramate acid (Compound 1-42 N)

< / BR>
17 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-hexadecanoyl-2,3,4,5,7 - pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

58 mg (0.08 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2-topiramate [obtained as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and the resulting solution was added 10 mg (0.10 mmol) of triethylamine and 26 mg (0,0946 mmol) hexago time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as eluent, receiving 50 mg (yield 67%) of the named compound as a colorless amorphous substance.

Rf = 0,4 (1:1 = ethyl acetate:hexane).

[]2D5-11,0o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 939 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,20 - 1,40 (22H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.97 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

2,95 (1H, doublet, J = 5.0 Hz);

4,20 - 4,60 (6H, multiplet);

the 5.25 (1H, multiplet);

5,97 (1H, doublet, J = 2.6 Hz);

of 6.65 (1H, doublet, J = 8.5 Hz);

6,93 (1H, singlet);

7,20 - 7,40 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

17 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate acid

45 mg (0.05 mmol) diphenylmethyl 5 - acetamido-4 - bis-t-BU the Chennai, as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 28 mg (yield 73%) of the named compound as a colourless solid.

Rf = 0.4 ( of 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5+19,7o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 573 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,25 - 1,40 (16H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 7.0 Hz);

4,10 - and 4.40 (5H, multiplet);

4,45 - 4,70 (2H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 2,4 Hz).

EXAMPLE 18

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O - octadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate acid (Compound N 1-43)

< / BR>
18 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxide,08 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-topiramate [received, as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and the resulting solution was added 10 mg (0.10 mmol) of triethylamine and 29 mg (0,094 mmol) octadecanoyl chloride, while cooling with ice. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel, using a 1:1 by volume mixture of ethyl acetate and hexane as eluent, receiving 51 mg (yield 67%) of the named compound as a colorless amorphous substance.

Rf = 0,5 (1:1 = ethyl acetate:hexane).

[]2D5-8,1o(C = 0,16, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 967 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,20 - 1,40 (30H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.97 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

2,95 (1H, doublet, J = 5,0 ;

6,93 (1H, singlet);

7,20 - 7,40 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

18 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-octadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D - galacto-non-2-topiramate acid

45 mg (0,047 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 octadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 24 mg (yield 62%) of the named compound as a colourless solid.

Rf = 0.4 (of 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5+14,3o(C = 0,15, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 601 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,25 - 1,40 (28H, multiplet);

1,55 2H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 2,4 Hz).

EXAMPLE 19

Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-acetyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound 1-54 N)

< / BR>
19 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-8,9-di-O-acetyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

58 mg (0,083 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2 - topiramate [obtained as described in Example 13 (i)] dissolved in 2 ml of pyridine, and to the obtained solution under cooling with ice, add 0.5 ml of acetic anhydride. The mixture was then stirred at room temperature for 3 hours. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of 1 N aqueous solution of hydrochloric acid, and the organic layer is separated and washed with saturated aqueous acidic sodium carbonate and then saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography n is called compound as a colorless amorphous substance.

Rf = 0,47 (1:1 = hexane:ethyl acetate).

[]2D5+2,5o(C = 0,12, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 785 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

to 1.99 (3H, singlet);

2,04 (3H, singlet);

2,07 (3H, singlet);

4,00 - 4,30 (3H, multiplet);

of 4.75 (1H, doublet, J = 13 Hz);

4,80 (1H, doublet of doublets, J = 7.5 and 45 Hz);

5,20 (1H, double doublet of doublets, J = 1,0, 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

of 5.92 (1H, doublet, J = 2,4 Hz);

6,72 (1H, doublet, J = 7.5 Hz);

6,94 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

19 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-acetyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid

50 mg (0,064 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di acetyl-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation at PC isopropanol, ethyl acetate and water as eluent, receiving 23 mg (yield 56%) of the named compound as a colourless solid.

Rf = 0,16 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +36,9o(C = 0,15, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 419 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

a 2.00 (3H, singlet);

2,03 (3H, singlet);

is 2.05 (3H, singlet);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.50 (1H, multiplet);

5,70 (1H, doublet, J = 3.0 Hz).

EXAMPLE 20

Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-propionyl 2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2 - topiramate acid (Compound 1-55 N)

< / BR>
20 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t-butoxycarbonylamino)-8,9-di-O-propionyl 2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

52 mg (0,074 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2-topiramate [obtained as described in Example 13 (i)] dissolved in 2 ml of pyridine, and to the obtained solution under cooling with ice, add 0.5 ml of propionic anhydride. The mixture is then lane 2-layer solution of 5 ml of ethyl acetate and 3 ml of 1N aqueous solution of hydrochloric acid, and the organic layer is separated and washed with saturated aqueous acidic sodium carbonate and then saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel, using a 1: 1 by volume mixture of hexane and ethyl acetate as eluent, receiving 54 mg (yield 90%) of the named compound as a colorless amorphous substance.

Rf = 0,54 (1:1 = hexane:ethyl acetate).

[]2D5= +9,6o(C = 0,14, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 813 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

a 1.11 (9H, triplet, 7.5 Hz);

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

2,04 (3H, singlet);

of 2.20 to 2.35 (4H, multiplet);

4,00 - 4,30 (3H, multiplet);

of 4.75 (1H, doublet, J = 13 Hz);

4,80 (1H, doublet of doublets, J = 7.5 and 45 Hz);

5,20 (1H, double doublet of doublets, J = 1,0, 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

of 5.92 (1H, doublet, J = 2,4 Hz);

6,72 (1H, doublet, J = 7.5 Hz);

6,94 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

20 (ii) Salt triperoxonane acid, 5-acetamido-4-Guan is 7 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di propionyl 2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2 - topiramate [received, as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and hexane as eluent, receiving 24 mg (yield 63%) of the named compound as a colourless solid.

Rf = 0.25 in ( 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +32,3o(C = 0,14, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 447 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 1.10 (6H, triplet, J = 7.5 Hz);

a 2.00 (3H, singlet);

of 2.35 (4H, Quartet, J = 7.5 Hz);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.50 (1H, multiplet);

the ceiling of 5.60 (1H, doublet, J = 3.0 Hz).

EXAMPLE 21

Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound 1-58 N)

< / BR>
21 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t-butoxycarbonylamino)-8,9-di-O-Huck is atamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane 7 fluorescent glycero galacto-non-2-topiramate [received, as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 19 mg (0,17 mmol) of 4-dimethylaminopyridine and 19 mg (0.14 mmol) hexanoyl chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 3:1 by volume mixture of hexane and ethyl acetate as eluent, receiving 49 mg (yield 87%) of the named compound as a colorless amorphous substance.

Rf = 0.28 in (3:1 = hexane:ethyl acetate).

[]2D5= +6,5o(C = 0,10, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 897 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,80 - 1,00 (6H, multiplet);

1,20 - 1,40 (8H, multiplet);

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

1,50 - 1,70 (4H, multiplet);

to 1.98 (3H, singlet) is in, J = 7.4 and 45 Hz);

by 5.18 (1H, double doublet of doublets, J = 1,0, 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

to 5.93 (1H, doublet, J = 2,4 Hz);

6,70 (1H, doublet, J = 7.5 Hz);

6,93 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

21 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid

42 mg (0,047 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di hexanoyl-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 21 mg (yield 59%) of the named compound as a colourless solid.

Rf = 0.34 in ( 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +23,7o(C = 0,11, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 531 (M+
1,20 - 1,40 (8H, multiplet);

1,55 - 1,70 (4H, multiplet);

a 2.00 (3H, singlet);

of 2.30 (2H, triplet, J = 7.5 Hz);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.55 (1H, multiplet);

the 5.65 (1H, doublet, J = 3.0 Hz).

EXAMPLE 22

Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-O-decanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound 1-61 N)

< / BR>
22 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-8,9-di-O-decanoyl-2,3,4,5,7-pentadecane-7 - fluorescent-D-glycero-D-galacto-non-2-topiramate

42 mg (0.06 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - fluorescent glycero galacto-non-2-topiramate [obtained as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 18 mg (0.15 mmol) 4-dimethylaminopyridine and 26 mg (0.14 mmol) decanoyl chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then su is the residue purified column chromatography on silica gel, using a 3:1 by volume mixture of hexane and ethyl acetate as eluent, receiving 52 mg (yield 86%) of the titled compound as a colorless amorphous substance.

Rf = 0.28 in (3:1 = hexane:ethyl acetate).

[]2D5+13,3o(C = 0,17, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 1009 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,80 - 0,90 (6H, multiplet);

1,20 - 1,40 (24H, multiplet);

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

1,50 - of 1.65 (4H, multiplet);

to 1.98 (3H, singlet);

2,20 - of 2.30 (4H, multiplet);

of 4.75 (1H, doublet, J = 13 Hz);

4,80 (1H, doublet of doublets, J = 7.5 and 45 Hz);

5,20 (1H, double doublet of doublets, J = 1,0, 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

of 5.92 (1H, doublet, J = 2,4 Hz);

of 6.65 (1H, doublet, J = 7.5 Hz);

6,93 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

22 (ii) Salt triperoxonane acid, 5-acetamido-4 - guanidino-8,9-di-O-decanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate acid

45 mg (0.045 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)8.9bn decanoyl-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] RA is Oh temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 29 mg (75% yield) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +20,6o(C = 0,14, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 643 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (6H, multiplet);

1,20 - 1,40 (24H, multiplet);

1,55 - 1,70 (4H, multiplet);

a 2.00 (3H, singlet);

of 2.30 (2H, triplet, J = 7.0 Hz);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.55 (1H, multiplet);

5,70 (1H, doublet, J = 3.0 Hz).

EXAMPLE 23

Salt triperoxonane acid acetamido-4-guanidino-8,9-di-O-decanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound N 1-63)

< / BR>
23(i) Diphenylmethyl 5-acetamido-4-(N, N'-bis-t-butoxycarbonylamino)-8,9-di-O-deletion - 2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

43 mg (0.06 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butok the d 13 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 19 mg (0.15 mmol) 4-dimethylaminopyridine and 26 mg (0.14 mmol) deletion of chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 3:1 by volume mixture of hexane and ethyl acetate as eluent, receiving 60 mg (yield 87%) of the named compound as a colorless amorphous substance.

Rf = 0.28 in (3:1 = hexane:ethyl acetate).

[]2D5= +15,5o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 1121 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,80 - 0,90 (6H, multiplet);

1,20 - 1,40 (40H, multiplet);

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

1,50 - of 1.65 (4H, multiplet);

to 1.98 (3H, singlet);

2,20 - of 2.30 (4H, multiplet);

4,00 - 4,30 (3H, multipl is,0, at 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

to 5.93 (1H, doublet, J = 2,4 Hz);

of 6.66 (1H, doublet, J = 7.5 Hz);

6,93 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

23 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-deletion-2,3,4,5,7-pentadecane-7 - fluorescent-D-glycero-D-galacto-non-2-topiramate acid

52 mg (0.046 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di deletion - 2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml, 3:1, by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2: 5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 38 mg (yield 83%) of the named compound as a colourless solid.

Rf = 0,3 ( 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +28,0o(C = 0,16, CH3OH).

Mass spectrum 755 (the Belarusian library Association, FAB) m/z 545 (M++H).

1H-Range nuclear 1,55 - to 1.70 (4H, multiplet);

a 2.00 (3H, singlet);

of 2.30 (2H, triplet, J = 7.0 Hz);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.55 (1H, multiplet);

5,70 (1H, doublet, J = 3.0 Hz).

EXAMPLE 24

Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound N 1-64)

< / BR>
24 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-8,9-di-O-hexadecanoyl-2,3,4,5,7-pentadecane - 7-fluorescent-D-glycero-D-galacto-non-2-topiramate

37 mg (0,053 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7 - pentadecane-7 - fluorescent glycero galacto-non-2-topiramate [obtained as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 16 mg (0.13 mmol) of 4-dimethylaminopyridine and 34 mg (0.12 mmol) hexadecanoyl chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time, the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sulfate chromatography on silica gel, using a 3:1 by volume mixture of hexane and ethyl acetate as eluent, receiving 52 mg (yield 84%) of the named compound as a colorless amorphous substance.

Rf = 0,3 (3:1 = hexane:ethyl acetate).

[]2D5= +10,9o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/C 1177 (+M+H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,80 - 0,90 (6H, multiplet);

1,20 - 1,40 (48H, multiplet);

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

1,50 - of 1.65 (4H, multiplet);

to 1.98 (3H, singlet);

2,20 - of 2.30 (4H, multiplet);

4,00 - 4,30 (3H, multiplet);

of 4.75 (1H, doublet, J=13 Hz);

4,80 (1H, doublet of doublets, J = 7.5 and 45 Hz);

5,20 (1H, double doublet of doublets, J = 1,0, 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

of 5.92 (1H, doublet, J = 2,4 Hz);

of 6.65 (1H, doublet, J = 7.5 Hz);

6,93 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

24 (ii) Salt triperoxonane acid, 5-acetamido-4 - guanidino-8,9-di-O-hexadecanoyl-2,3,4,5,7-pentadecane-7 - fluorescent-D-glycero-D-galacto-non-2-topiramate acid

42 mg (being 0.036 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di-hexadecanoyl - 2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2 - topiramate [acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2: 5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 22 mg (yield 59%) of the named compound as a colourless solid.

Rf = 0.4 (of 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +15,3o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 811 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

0,85 - 0,95 (6H, multiplet);

1,20 - 1,40 (48H, multiplet);

1,55 - 1,70 (4H, multiplet);

a 2.00 (3H, singlet);

of 2.30 (2H, triplet, J = 7.0 Hz);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.55 (1H, multiplet);

5,70 (1H, doublet, J = 3.0 Hz).

EXAMPLE 25

Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-octadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid (Compound N 65-1)

< / BR>
25(i) Diphenylmethyl 5-acetamido-4-(N, N'-bis-t - butoxycarbonylamino)-8,9-di-O-octadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-noxi-7 - fluorescent glycero galacto-non-2-topiramate [received, as described in Example 13 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 15 mg (0.13 mmol) of triethylamine and 35 mg (0,115 mmol) octadecanoyl chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 3:1 by volume mixture of hexane and ethyl acetate as eluent, receiving 57 mg (yield 93%) of the named compound as a colorless amorphous substance.

Rf = 0,3 (3:1 = hexane:ethyl acetate).

[]2D5= +11,2o(C = 0,18, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 1233 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,80 - 0,90 (6H, multiplet);

1,20 - 1,40 (56H, multiplet);

to 1.48 (9H, singlet);

for 1.49 (9H, singlet);

1,50 - of 1.65 (4H, multiplet);

to 1.98 (3H, singlet);

5,20 (1H, double doublet of doublets, J = 1,0, 9.0 and 9.0 Hz);

of 5.50 (1H, multiplet);

of 5.92 (1H, doublet, J = 2,4 Hz);

of 6.65 (1H, doublet, J = 7.5 Hz);

6,93 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

at 8.60 (1H, doublet, J = 8.5 Hz).

25 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-8,9-di-O-octadecanoyl-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate acid

47 mg (0.04 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di octadecanoyl - 2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2: 5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 28 mg (yield 67%) of the named compound as a colourless solid.

Rf= 0, 4 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +14,5o(C = 0,14, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 867 (M++H).


1,20 - 1,40 (56H, multiplet);

1,55 - 1,70 (4H, multiplet);

a 2.00 (3H, singlet);

of 2.30 (2H, triplet, J = 7.0 Hz);

4,10 - and 4.40 (4H, multiplet);

4,70 - 5,00 (2H, multiplet);

of 5.55 (1H, multiplet);

5,70 (1H, doublet, J = 3.0 Hz).

EXAMPLE 26

Salt triperoxonane acid hexadecyl 5 - acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D - galacto-non-2-topiramate (Compound 1-6 N)

< / BR>
26 (i) Hexadecyl 5-acetamido-4-azido-8,9-O-isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

275 mg (0,74 mmol) of methyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in Example 7 (i)] is dissolved in 7 ml of 6:1 by volume mixture of methanol and water, and the resulting solution was added of 0.82 ml of a 1M aqueous solution of potassium hydroxide. The mixture is then stirred at room temperature for 2 hours. At the end of this time the solvent is removed by distillation under reduced pressure and dried under reduced pressure at room temperature for 2 hours, obtaining a pale yellow solid. The solid is dissolved in 8 ml of acetonitrile, and the resulting solution was added 195 mg (0,74 mmol) of 18-crown-6 and 677 mg (2.2 mmol) eritel removed by distillation under reduced pressure. 2-layer solution of 15 ml of ethyl acetate and 10 ml of a saturated aqueous solution of acid sodium carbonate was poured on the obtained residue, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50: 1, by volume mixture of methylene chloride and methanol as eluent, receiving 240 mg (yield 56%) of the named compound as a colorless amorphous substance.

Rf = 0.50 (a 20:1 = methylene chloride:methanol).

[]2D5= +65,0o(C=0,5, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 583 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 0.80 - 0.95 (3H, multiplet);

1,20 - 1,40 (28H, multiplet);

of 1.37 (3H, singlet);

of 1.42 (3H, singlet);

1,60 - 1,80 (2H, multiplet);

is 2.05 (3H, singlet);

4,10 - 4,30 (3H, multiplet);

however, 4.40 (1H, multiplet);

4,72 (1H, double doublet of doublets, J = 1,3, 5,3 and 47.0 Hz);

the 4.90 (1H, doublet of doublets, J=2.4 and 9.3 Hz);

to 4.92 (1H, double doublet of doublets, J = 1,4, 10,0 and 28.0 Hz) ;

of 5.92 (1H, doublet, J = 7,2 Hz);

5,94 (1H, doublet, J = 2,6 Hz).


240 mg (0.41 mmol) hexadecyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 10 ml of methanol, and the resulting solution was added 60 mg of lindlar catalyst. Then the mixture is stirred in hydrogen atmosphere for 2 hours. At the end of this time the catalyst was separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 4 ml of dimethylformamide, and the resulting solution was added 145 mg (0,53 mmol) di-t-butoxycarbonylamino, 106 mg (1.05 mmol) of triethylamine and 142 mg (of 0.53 mmol) of mercury chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the solid is separated by filtration, and the filtrate is poured into 2-layer solution of 15 ml of ethyl acetate and 10 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel, using a 1:2 by volume mixture of ethyl acetate and S="ptx2">

Rf = 0.40 in (20:1 = methylene chloride:methanol).

[]2D5= -11,6o(C = 0,06, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 799 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 0.80 - 0.95 (3H, multiplet);

1,20 - 1,40 (28H, multiplet);

of 1.37 (3H, singlet);

of 1.41 (3H, singlet);

for 1.49 (9H, singlet);

of 1.50 (9H, singlet);

1,60 - 1,80 (2H, multiplet);

of 1.97 (3H, singlet);

4,10 - 4,30 (4H, multiplet);

4,40 with 4.65 (2H, multiplet);

5,20 (1H, double doublet of doublets, J = 2,4, 7.5 and 7.5 Hz);

of 5.83 (1H, doublet, J = 2,4 Hz);

the 5.65 (1H, doublet, J = 7.0 Hz);

at 8.60 (1H, doublet, J = 8.5 Hz).

26 (iii) Salt triperoxonane acid hexadecyl 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate

200 mg (0.25 mmol) hexadecyl 5-acetamido-4 - bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 10 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and estate and water as eluent, receiving 130 mg (yield 77%) of the named compound as a colourless solid.

Rf = 0,55 (5:1:1 = t-butanol:acetic acid:water).

[]2D5= +14,7o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 559 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

0,70 - 0,85 (3H, multiplet);

1,10 - 1,30 (28H, multiplet);

1,60 - 1,80 (2H, multiplet);

a 2.00 (3H, singlet);

3,60 - of 3.85 (2H, multiplet);

4,00 - 4,30 (3H, multiplet);

4,50 - 4,80 (2H, multiplet);

5,88 (1H, singlet).

EXAMPLE 27

Salt triperoxonane acid octadecyl 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate (Compound 1-7 N)

< / BR>
27 (i) Octadecyl 5-acetamido-4-azido-8,9-O-isopropylidene - 2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

45 mg (0.12 mmol) of methyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in Example 7 (i)] is dissolved in 4 ml of 6:1 by volume mixture of methanol and water, and the resulting solution was added 0.13 mg 1M aqueous solution of potassium hydroxide. The mixture is then stirred at room temperature for 2 hours eigendom pressure at room temperature for 2 hours, receiving a pale yellow solid. This solid is dissolved in 2 ml of acetonitrile, and the resulting solution was added 322 mg (0.12 mmol) of 18-crown-6 and 121 mg (0.36 mmol) of octadecyl bromide. The mixture is then stirred at 80oC for 30 minutes. The obtained residue was poured into 2-layer solution of 7 ml of ethyl acetate and 5 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 2:1 by volume mixture of hexane and ethyl acetate as eluent, receiving 42 mg (yield 58%) of the named compound as a colorless amorphous substance.

Rf = 0.50 (a 20:1 = methylene chloride:methanol).

[]2D5= +76o(=0,05, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 611 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

0,85 - 0,95 (3H, multiplet);

1,20 - 1,40 (32H, multiplet);

of 1.37 (3H, singlet);

of 1.42 (3H, singlet);

1,60 - 1,80 (2H, multiplet);

is 2.05 (3H, singlet);

4,10 - 4,30 (3H, multip is = 2.6 and 9.5 Hz);

to 4.92 (1H, double doublet of doublets, J = 1,4, 10,0 and 28.0 Hz);

5,94 (1H, doublet, J = 7,2 Hz);

5,91 (1H, doublet, J = 2,6 Hz).

27 (ii) Octadecyl 5-acetamido-4-(N,N'-bis-t-butoxycarbonylamino) -8,9-O-isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent-D-glycero-D-galacto-non-2-topiramate

40 mg (of 0.066 mmol) octadecyl 5-acetamido-4-azido-8,9 isopropylidene-2,3,4,5,7-pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of methanol and there is added 10 mg of Lindlar catalyst. Then the mixture is stirred in hydrogen atmosphere for 2 hours. At the end of this time the catalyst was separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 2 ml of dimethylformamide, and then to the resulting solution was added 25 mg (0.09 mmol) of di-t-butoxycarbonylamino, 18 mg (0.18 mmol) of triethylamine and 25 mg (0.09 mmol) of mercury chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the solid is separated by filtration. The filtrate is poured into 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated water is th at reduced pressure. The resulting residue is purified column chromatography on silica gel, using a 1: 1 by volume mixture of hexane and ethyl acetate as eluent, receiving 39 mg (71% yield) of the named compound as a colorless viscous substance.

Rf = 0.40 in (20:1 = methylene chloride:methanol).

[]2D5= -7,4o(C = 0,10, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 827(M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 0.80 - 0.95 (3H, multiplet);

1,20 - 1,40 (32H, multiplet);

of 1.37 (3H, singlet);

of 1.41 (3H, singlet);

for 1.49 (9H, singlet);

of 1.50 (9H, singlet);

1,60 - 1,80 (2H, multiplet);

of 1.97 (3H, singlet);

4,10 - 4,30 (4H, multiplet);

4,40 with 4.65 (2H, multiplet);

5,20 (1H, double doublet of doublets, J = 2,4, 7.5 and 7.5 Hz);

of 5.83 (1H, doublet, J = 2.3 Hz);

the 5.65 (1H, doublet, J = 7.0 Hz);

at 8.60 (1H, doublet, J = 8.5 Hz).

27 (iii) Salt triperoxonane acid octadecyl 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-fluorescent-D - glycero-D-galacto-non-2-topiramate

30 mg (0.04 mmol) octadecyl 5-acetamido-4 - bis - t-butoxycarbonylamino)8.9bn isopropylidene-2,3,4,5,7 - pentadecane-7-fluorescent glycero galacto-non-2-topiramate [obtained as described in stage (ii) above] dissolved in 3 ml of 3:1, 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2: 8:1, by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 20 mg (yield 79%) of the named compound as a colourless solid.

Rf = 0,55 (5:1:1 = t-butanol:acetic acid:water).

[]2D5= +14,0o(C = 0,10, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 587 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz), (ppm):

0,70 - 0,85 (3H, multiplet);

1,10 - 1,30 (32H, multiplet);

1,60 - 1,80 (2H, multiplet);

a 2.00 (3H, singlet);

3,60 - of 3.85 (2H, multiplet);

4,00 - 4,30 (3H, multiplet);

4,50 - 4,80 (2H, multiplet);

5,88 (1H, singlet).

EXAMPLE 28

Salt triperoxonane acid, 5-acetamido-4 - guanidino-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non - 2-topiramate acid (Compound N 163-1)

< / BR>
28 (i) of Benzyl N-acetyl-3,6-di-O-benzyl-4-O-methyl-D-glucosamine.

4,48 g (9,12 mmol) benzyl acetyl-3,6-di benzyl -- glucosamine [obtained by the method described in Carbohydrate Res. 83, 163-169 (1980)] are dissolved in 50 ml of dimethylformamide, and to the obtained rest the chickpeas, then add at 0oC 1.42 g (10.0 mmol) under the conditions, and the mixture is stirred at room temperature for another 5 hours. At the end of this time the reaction mixture was poured into a 2-layer solution of 100 ml of ethyl acetate and 50 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 4: 1 by volume mixture of methylene chloride and ethyl acetate as eluent, getting 3.6 g (yield 78%) of the named compound as a colourless solid.

Rf = 0,55 (20:1 = methylene chloride:methanol).

[]2D5= +126o(C = 1,15, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 506(M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.80 (3H, singlet);

of 3.48 (3H, singlet);

3,40 - of 3.80 (5H, multiplet);

to 4.23 (1H, double doublet of doublets, J = 3,5, of 10.0 and 10.0 Hz);

4,40 - 4,90 (7H, multiplet);

the 5.25 (1H, doublet, J = 10.0 Hz);

7,20 - 7,40 (15H, multiplet).

28 (ii) N-Acetyl-4-O-methyl-D-glucose is yse] dissolved in 40 ml of acetic acid, to the resulting solution was added 5.0 g of palladium-on-carbon. Then the mixture is stirred in hydrogen atmosphere at 3 ATM for 30 minutes. At the end of this time the catalyst was separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using the method of gradient elution with mixtures of methylene chloride and methanol in the range from 10:1 to 5: 1 by volume as the eluent, receiving 1.42 g (yield 83%) of the named compound as a colourless solid.

Rf = 0.35 in (5:1 = methylene chloride:methanol).

[]2D5= +72,2o(C = 2,9, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 236 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

to 1.98 (3H, singlet);

of 3.57 (3H, singlet);

3,60 - of 3.80 (6H, multiplet);

of 5.05 (1H, doublet, J = 3.2 Hz).

28 (iii) 5-acetamido-3,5-dideoxy-7-O-methyl-D-glycero-D-galacto-2-neurophilosophy (nonuropyranosoic) acid

5.0 g (21,3 mmol) acetyl-4 methyl glucosamine [obtained as described in stage (ii) above] dissolved in distilled water and the resulting solution was added 100 mg of sodium azide and 5.0 g (to 45.5 mmol) pyruvate nutriti then added to the mixture of 25 mg (660 F) of aldolase acetylneuraminic acid (produced by TOYOBO K. K. ), and the mixture is stirred at 20oC for 3 days. At the end of this time the reaction mixture absoluut using Dowex h (H+) resin (Dowex is a trademark), and purified column chromatography using Dowex 1 (HCOOH), elute 1.0 M aqueous solution of formic acid, obtaining 1.8 g (yield 26%) of the named compound as a colorless viscous substance.

Rf = 0,30 ( 4:1:1 = isopropanol:acetic acid:water).

[]2D5= -19,7o(C = 1,2, H2O).

Mass spectrum (of the Belarusian library Association, FAB) m/z 324 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

of 1.80 (1H, doublet of doublets, J = to 12.0 and 12.0 Hz);

a 2.00 (3H, singlet);

2,10 (1H, doublet of doublets, J = 4.5 and 12.0 Hz);

of 3.48 (3H, singlet);

3,50 - of 3.80 (7H, multiplet).

28 (iv) of Methyl 5-acetamido-3,5-dideoxy-7-O-methyl-D-glycero-D-galacto-2-noneuropeans (nonuropyranosoate)

680 mg (2.10 mmol) of 5-acetamido-3,5-dideoxy-7 methyl glycero galacto-2-neurophilosophy acid [obtained as described in stage (iii) above] dissolved in 20 ml of methanol, and the resulting solution was added 500 mg of Dowex h (H+) cation exchange resin (Dowex is a trademark). The mixture is then stirred at room temperature for 15 casoa under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 5:1 by volume mixture of methylene chloride and methanol as eluent, receiving 340 mg (yield 48%) of the named compound as a colorless amorphous substance.

Rf = 0.15 in (5:1 = methylene chloride:methanol).

[]2D5= +30,2o(C = 1,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 338 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

1,90 (1H, doublet of doublets, J = to 12.0 and 14.0 Hz);

a 2.00 (3H, singlet);

of 2.16 (1H, doublet of doublets, J = 4.5 and 12.0 Hz);

3,40 (1H, multiplet);

of 3.45 (3H, singlet);

3,50 - of 3.80 (3H, multiplet);

of 3.77 (3H, singlet);

of 3.80 - 4.00 points (2H, multiplet);

4,20 (1H, doublet of doublets, J = 1.5 and 9.5 Hz).

28 (v) of Methyl 5-acetamido-4,8,9-tri-O-acetyl-2,3,5-trideoxy-7-O-methyl-D-glycero-D-galacto-2-topiramate

686 mg (2.03 mmol) of methyl 5-acetamido-3,5-dideoxy-7 - methyl-glycero galacto-2-neurodermatitis [obtained as described in stage (iv) above] dissolved in a mixture of 10 ml of pyridine and 10 ml of acetic anhydride, and the mixture is stirred at room temperature for 15 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and ostay temperature for 15 hours. At the end of this time the mixture is dissolved in benzene and the resulting solution was added 182 mg (1.20 mmol) of 1,8-diazabicyclo[5.4.0]-7-undecene, and the mixture is stirred at room temperature for 2 hours. Then the reaction mixture was poured in a 2-layer solution of 30 ml of methylene chloride and 15 ml of a saturated aqueous solution of ammonium chloride, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50: 1, by volume mixture of methylene chloride and methanol as eluent, getting 310 mg (yield 34%) of the named compound as a colorless amorphous substance.

Rf = 0,30 (20:1 = methylene chloride:methanol).

[]2D5= +206o(C=0,15, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 446 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

a 2.00 (3H, singlet);

to 2.06 (3H, singlet);

of 2.08 (3H, singlet);

of 2.10 (3H, singlet);

3,50 (3H, singlet);

the 3.65 (1H, doublet of doublets, J = 3.0 and 3.0 Hz);

of 3.80 (3H, singlet);

4,20 is 4.35 (2H, multiplet);

of 5.55 (1H, doublet, J = 8.0 Hz);

6,00 (1H, doublet, J = 2,8 Hz).

28 (vi) of Methyl 5-acetamido-4-azido-8,9-di-O-acetyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate

303 mg (0.67 mmol) of methyl 5-acetamido-4,8,9-tri acetyl-2,3,5-trideoxy-7 methyl glycero galacto-non-2 - topiramate [obtained as described in stage (v) above] dissolved in 10 ml of anhydrous methylene chloride, and the resulting solution was added 22 mg (0.67 mmol) of methanol. 956 mg (6,74 mmol) of the complex of boron TRIFLUORIDE-diethyl ether is added to the resulting mixture in a nitrogen atmosphere, and the mixture is stirred at room temperature for 24 hours. At the end of this time the reaction mixture was poured into a mixture of 20 ml of water, 10 g of ice, 5 g of solid acid sodium carbonate and 20 ml of ethyl acetate, and the mixture is vigorously stirred for 10 minutes. The organic layer is then separated, washed with 10 ml saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The obtained residue (270 mg) was dissolved in 10 ml of dimethylformamide, and the resulting solution was added 270 mg of cation exchange resin [Dowex h (H+) - Dowex is a trademark] and 90 mg (1.37 mmol) of the azide intothree tdelay filtering, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 2-layer solution of 20 ml of ethyl acetate and 10 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 250 mg (yield 70%) of the named compound as a colorless viscous substance.

Rf = 0,30 (20:1 = methylene chloride:methanol).

[]2D5= +97,2o(C = 0,25, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 429 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

to 2.06 (6H, singlet);

of 2.10 (3H, singlet);

3,50 (3H, singlet);

the 3.65 (1H, doublet of doublets, J = 1.8 and 4.0 Hz);

of 3.80 (3H, singlet);

of 4.25 (1H, doublet of doublets, J = 5.0 and 12.0 Hz);

4,45 - 4,55 (2H, multiplet);

of 4.75 (1H, doublet of doublets, J = 3.2 and 12.0 Hz);

to 5.35 (1H, multiplet);

5,52 (1H, doublet, J = 8,2 Hz);

5,98 (1H, doublet, J = 2.7 Hz).

28 (vii) of Methyl 5-acetamido-4-(N,N'-bis

80 mg (0.42 mmol) of methyl 5-acetamido-4-azido-8,9-di acetyl-2,3,4,5,7-pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in stage (vi) above] dissolved in 10 ml of methanol, and the resulting solution was added 130 mg of Lindlar catalyst. Then the mixture is stirred in hydrogen atmosphere for 2 hours. At the end of this time the catalyst was separated by filtration, and the solvent is removed by distillation under reduced pressure. The obtained residue (120 mg) dissolved in 10 ml of dimethylformamide, and the resulting solution was added 100 mg (from 0.37 mmol) di-t-butoxycarbonylamino, 75 mg (0,74 mmol) of triethylamine and 100 mg (from 0.37 mmol) of mercury chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the solid is separated by filtration, and the filtrate is poured into 2-layer solution of 10 ml of ethyl acetate and 50 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated, washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 2:1 by volume mixture of hexane and society.

Rf = 0.50 (a 20:1 = methylene chloride:methanol) .

[]2D5= +2,8o(C = 0,65, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 645 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

for 1.49 (9H, singlet);

of 1.50 (9H, singlet);

of 1.97 (3H, singlet);

is 2.05 (3H, singlet);

2,07 (3H, singlet);

to 3.52 (3H, singlet);

3,55 (1H, multiplet);

of 3.78 (3H, singlet);

4,10 (1H, doublet of doublets, J = 1.0 and 10.5 Hz);

4,25 - and 4.40 (2H, multiplet);

4,82 (1H, doublet of doublets, J = 3.2 and 12.0 Hz);

5,12 (1H, double doublet of doublets, J = 2.5 and for 11.0 and 11.0 Hz);

and 5.30 (1H, multiplet);

to 5.85 (1H, doublet, J = 2.3 Hz);

6.35mm (1H, doublet, J = 8,8 Hz).

28 (viii) Salt triperoxonane acid, 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid

53 mg (0,083 mmol) of methyl 5-acetamido-4 - bis-t - butoxycarbonylamino)-8,9-di acetyl-2,3,4,5,7 - pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in stage (vii) above] dissolved in 2 ml of methanol, and the resulting solution was added 0.2 ml O 1 N methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction is under reduced pressure. The resulting residue is dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is dissolved in 1 ml of distilled water. 72 ál of 1N aqueous sodium hydroxide solution is then added to the reaction mixture, which was then stirred at room temperature for 1 hour. At the end of this time the reaction mixture is neutralized Dowex h (H+) resin (Dowex is a trademark) and then water is removed by distillation. The resulting residue is purified column chromatography on silica gel using 5:1:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 24 mg (yield 85%) of the named compound as a colourless solid.

Rf = 0,30 ( 4:1:1 = isopropanol:acetic acid:water).

[]2D5= -9,3o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 347 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

a 2.00 (3H, singlet);

3,37 (3H, singlet);

3,55 (1H, doublet, J = 8.5 Hz);

the 3.65 (1H, doublet of doublets, J = 5.0 and 12 Hz);

3,90.

EXAMPLE 29

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-deletion-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 163-41)

< / BR>
29 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-2,3,4,5,7-pentadecane-7-methoxy-D-glycero - D-galacto-non-2-topiramate

87 mg (0.14 mmol) of methyl 5-acetamido-4 - bis-t - butoxycarbonylamino)-8,9-di acetyl-2,3,4,5,7 - pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in Example 28 (vii)] dissolved in 5 ml of methanol, and the resulting solution was added 2 ml of 0.4 N methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture was neutralized with 4 M solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 4 ml of distilled water and the resulting solution was added 0.2 ml of 1 N aqueous sodium hydroxide solution. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture was neutralized with 4 M solution of hydrogen chloride in dioxane, and then water is removed di is initiatoren and 50 mg (0.38 mmol) of the complex of boron TRIFLUORIDE-diethyl ether is added to the resulting solution. The mixture is then stirred at room temperature for 2 hours. At the end of this time add acetic acid, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 20:1 by volume mixture of methylene chloride and methanol as eluent, receiving 29 mg (30% yield) of the named compound as a colorless amorphous substance.

Rf = 0.3 to (20:1 = methylene chloride:methanol).

[]2D5= +22,0o(C=0,4, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 713 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 1.46 (9H, singlet);

of 1.52 (9H, singlet);

of 1.95 (3H, singlet);

of 3.48 (1H, doublet, J = 9.0 Hz);

3,68 (1H, doublet of doublets, J = 4.0 and 12 Hz);

of 3.85 (1H, doublet of doublets, J = 2.5 and 12 Hz);

of 3.95 (1H, multiplet);

4,32 (1H, doublet of doublets, J = 10 and 10 Hz);

4,43 (1H, doublet, J = 10 Hz);

of 5.05 (1H, doublet of doublets, J = 2.2 and 10 Hz);

of 6.02 (1H, doublet, J = 2.2 Hz);

make 6.90 (1H, singlet);

7,20 is 7.50 (10H, multiplet).

29 (ii) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-deletion-2,3,4,5,7 - pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate
o
C for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 22 mg (yield 61%) of the named compound as a colorless amorphous substance.

Rf = 0.45 in (20:1 = methylene chloride:methanol).

[]2D5= +40,5o(C = 0,2, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/C 923 (M++H).

1H-Spectrum nuclear magnetic resonance (CHCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

1,20 - 1,30 (20H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

to 1.98 (3H, singlet);

of 2.33 (2H the doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,18 (1H, doublet, J = 8.7 Hz);

6,92 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

29 (iii) Salt triperoxonane acid, 5-acetamido-guanidino-9-O-deletion-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid

22 mg (0,024 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 deletion - 2,3,4,5,7-pentadecane-7-methoxy glycero galacto-non-2 - topiramate [obtained as described in stage (ii)] was dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent to give 10 mg (yield 74%) of the named compound as a colourless solid.

Rf = 0.4 (of 2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +24,0o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 557 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz
is 2.37 (2H, triplet, J = 7.5 Hz);

to 3.38 (3H, singlet);

of 3.45 (1H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

EXAMPLE 30

Salt triperoxonane acid, 5-acetamido-4 - guanidino-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2 - enoeou (enoic) acid (Compound N 199-1)

< / BR>
30 (i) Benzyl N-acetyl-3,6-di-O-benzyl-4-O-ethyl-D-glucosamine

8,35 g (16,8 mmol) benzyl acetyl-3,6-di benzyl -- glucosamine [obtained according to the method described in Carbohydrate Res. 83, 163-169 (1980)] was dissolved in 80 ml of dimethylformamide, and the resulting solution was added 1.84 g (42,2 mmol) of sodium hydride. The mixture is then stirred at room temperature for 30 minutes, after which the mixture at 0oC add 2.86 g (18.5 mmol) of ethyliodide, and the mixture is stirred at room temperature for 5 hours. At the end of this time the reaction mixture was poured into a 2-layer solution of 200 ml of ethyl acetate and 100 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then it is dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel, speedmenu in the form of a colorless solid.

Rf = 0,55 (20:1 = methylene chloride:methanol).

[]2D5= +123o(s = 2,3, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 520 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.10 (3H, triplet, J = 7.0 Hz);

of 1.80 (3H, singlet);

3,40 - 3,90 (7H, multiplet);

is 4.21 (1H, double doublet of doublets, J = 3,5, of 10.0 and 10.0 Hz);

4,40 - 4,90 (7H, multiplet);

with 5.22 (1H, doublet, J = 10.0 Hz);

7,20 - 7,40 (15H, multiplet).

30 (ii) N-Acetyl-4-O-ethyl-D-glucosamine

7.0 g (a 13.4 mmol) benzyl acetyl-3,6-di-benzyl-4 - ethyl glucosamine [obtained as described in stage (i) above] was dissolved in 60 ml of acetic acid and the resulting solution was added 10 g of palladium-on-carbon. Then the mixture is stirred in hydrogen atmosphere at a pressure of 3 ATM for 3 hours. At the end of this time the catalyst was separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using the method of gradient elution with mixtures of methylene chloride and methanol in the range from 10:1 to 5:1 by volume as the eluent, obtaining 2.4 g (yield 81%) of the named compound as a colourless solid.

Rf is ACC-spectrum (the Belarusian library Association, FAB) m/z 250 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz), (ppm):

to 1.15 (3H, triplet, J = 7.0 Hz);

a 2.00 (3H, singlet);

of 3.33 (2H, Quartet, J = 7.0 Hz);

3,60 - 3,90 (6H, multiplet);

further 5.15 (1H, singlet).

30 (iii) 5-Acetamido-3,5-dideoxy-7-O-ethyl-D-glycero-D - galacto-2-neurophilosophy acid

5.0 g (20,1 mmol) acetyl-4-ethyl glucosamine [obtained as described in stage (iii) above] dissolved in distilled water and the resulting solution was added 100 mg of sodium azide and 5.0 g (to 45.5 mmol) of sodium pyruvate. the pH of the reaction mixture is brought to a value of 10-11 using 1N aqueous sodium hydroxide solution, then add a 25 mg (660 F) of aldolase acetyl-neuraminic acid (produced by TOYOBO K. K.), and the mixture is stirred at 20oC for 3 days. At the end of this time the reaction mixture absoluut using Dowex h (H+) resin (Dowex is a trademark) and purified using chromatography using Dowex h (H+) resin (Dowex is a trademark) with 1.0 M aqueous solution of formic acid as eluent, receiving 500 mg (yield of 7.4%) of the named compound as a colorless viscous substance.

Rf = 0,20 ( 4:1:1 = isopropanol:acetic acid:water).

[]2D2O, 270 MHz) (ppm):

of 1.05 (3H, triplet, J = 7.0 Hz);

of 1.80 (1H, doublet of doublets, J = to 12.0 and 12.0 Hz);

a 2.00 (3H, singlet);

of 2.20 (1H, doublet of doublets, J = 4.5 and 12.0 Hz);

3,50 - of 3.80 (7H, multiplet).

30 (iv) of Methyl 3 - acetamido-3,5-dideoxy-7-O-ethyl-D-glycero-D-galacto-2-noneuropeans

1.9 grams (5,64 mmol) of 5-acetamido-3,5-dideoxy-7 ethyl glycero galacto-2-neurophilosophy acid [obtained as described in stage (iii) above] dissolved in 60 ml of methanol, and the resulting solution was added 600 mg of cation exchange resin [Dowex h (H+) - Dowex is a trademark]. The mixture is then stirred at room temperature for 15 hours. At the end of this time Dowex h (H+) is separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 5:1 by volume mixture of methylene chloride and methanol as eluent, gaining 1.4 g (71% yield) of the named compound as a colorless amorphous substance.

Rf = 0.3 to (5:1 = methylene chloride:methanol).

[]2D5= -7,5o(C = 0,10, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 352 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (blet doublets, J = 4.5 and 12.0 Hz);

of 3.42 (1H, doublet of doublets, J = 1.5 and 8.0 Hz);

of 3.60 (2H, Quartet, J = 7.0 Hz);

of 3.77 (3H, singlet);

3,70 - 4,00 (4H, multiplet);

to 4.15 (1H, doublet of doublets, J = 1.5 and 9.5 Hz).

30 (v) Methyl 5-acetamido-4,8,9-tri-O-acetyl-2,3,5,7 - tetradeoxy-7-ethoxy-D-glycero-D-galacto-non-2-topiramate

1.4 g (3,99 mmol) of methyl 5-acetamido-3,5-dideoxy-7 - ethyl glycero galacto-2-neurodermatitis [obtained as described in stage (iv) above] dissolved in a mixture of 20 ml of pyridine and 10 ml of acetic anhydride, and the mixture is stirred at room temperature for 15 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is dissolved in 50 ml of a 4M solution of hydrogen chloride in dioxane. The mixture is then stirred at room temperature for 15 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is dissolved in benzene. Then to the reaction mixture add 952 mg (6,30 mmol) of 1,8-diazabicyclo [5.4.0]-7-undecene, and the mixture is stirred at room temperature for 2 hours. At the end of this time the reaction mixture was poured into a 2-layer solution of 30 ml of methylene chloride and 15 ml of a saturated aqueous solution of ammonium chloride, and organic SL is Oia, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, obtaining 1.1 g (yield 60%) of the named compound as a colorless amorphous substance.

Rf = 0,30 ( 20:1 = methylene chloride:methanol).

[]2D5= +24,1o(C = 0,5, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 460 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.20 (3H, triplet, J = 7.0 Hz);

to 1.98 (3H, singlet);

is 2.05 (3H, singlet);

of 2.08 (3H, singlet);

3,50 - of 3.80 (3H, multiplet);

of 3.80 (3H, singlet);

4,20 is 4.35 (2H, multiplet);

of 4.45 (1H, multiplet);

4,70 (1H, doublet of doublets, J = 3.2 and 12.0 Hz);

5,33 (1H, multiplet);

vs. 5.47 (1H, doublet of doublets, J = 3.3 and 7.0 Hz);

the 5.51 (1H, doublet, J = 7.0 Hz);

6,00 (1H, doublet, J = 3.3 Hz).

30 (vi) of Methyl 5-Acetamido-4-azido-8,9-di-O-acetyl-2,3,4,5,7 - pentadecane-7-ethoxy-D-glycero-D-galacto-non-topiramate

1000 mg (2,18 mmol) of methyl 5-acetamido-4,8,9 - tri acetyl-2,3,5,7-tetradeoxy-7 - ethoxy glycero galacto-non-2-topiramate [obtained as described in stage (v) above] dissolved in 20 ml of anhydrous stands arid boron-diethyl ether is added to the resulting mixture in a nitrogen atmosphere, and the mixture is stirred at room temperature for 24 hours. At the end of this time the reaction mixture was poured into a mixture of 50 ml of water, 10 g of ice, 10 g of solid acid sodium carbonate and 50 ml of ethyl acetate, and the mixture is vigorously stirred for 10 minutes. The organic layer is then washed with 10 ml saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The obtained residue (800 mg) is dissolved in 10 ml of dimethylformamide, and the resulting solution was added 800 mg of cation exchange resin [Dowex h (H+) - Dowex is a trademark] and 400 mg (0.15 mmol) of sodium azide. The mixture is then stirred at 90oC for 4 hours. At the end of this time Dowex h (H+) resin is separated by filtration, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 2-layer solution of 30 ml of ethyl acetate and 20 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer is separated and washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column hroa 600 mg (yield 63%) of the named compound as a colorless viscous substance.

Rf = 0,30 (20:1 = methylene chloride:methanol).

[]2D5= +72,6o(=0,05, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 443 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.25 (3H, triplet, J = 7.0 Hz);

of 2.09 (3H, singlet);

of 2.10 (3H, singlet);

to 2.13 (3H, singlet);

3,50 - of 3.80 (3H, multiplet);

of 3.80 (3H, singlet);

of 4.05 (1H, multiplet);

of 4.25 (1H, doublet of doublets, J = 5.0 and 12.0 Hz);

4,45 - 4,55 (2H, multiplet);

4,80 (1H, doublet of doublets, J = 3.2 and 12.0 Hz);

to 5.35 (1H, multiplet);

the 5.51 (1H, doublet, J = 8,2 Hz);

6,00 (1H, doublet, J = 2.7 Hz).

30 (vii) of Methyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-8,9-di-O-acetyl - 2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate

580 mg (1,31 mmol) of methyl 5-acetamido-4-azido-8,9-di - acetyl-2,3,4,5,7-pentadecane-7-ethoxy glycero galacto-non-2-topiramate [obtained as described in stage (vi) above] dissolved in 10 ml of methanol, and the resulting solution was added 270 mg of Lindlar catalyst. Then the mixture is stirred in hydrogen atmosphere for 2 hours. At the end of this time the catalyst was separated by filtration, and the solvent is removed by distillation under reduced pressure. The obtained residue (400 ultimatemenu, 300 mg (2,95 mmol) of triethylamine and 402 mg (1.48 mmol) of mercury chloride. The mixture is then stirred at room temperature for 1 hour. At the end of this time the solid is separated by filtration, and the filtrate is poured into 2-layer solution of 20 ml of ethyl acetate and 10 ml of a saturated aqueous solution of acid sodium carbonate. The organic layer is separated and washed with saturated aqueous sodium chloride and dried over anhydrous sodium sulfate, then the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 2:1 by volume mixture of hexane and ethyl acetate as eluent, getting 530 mg (yield 61%) of the named compound as a colorless amorphous substance.

Rf = 0.40 in (20:1 = methylene chloride:methanol).

[]2D5= +2,8o(C = 0,5, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 659 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.20 (3H, triplet, J = 7.0 Hz);

for 1.49 (9H, singlet);

of 1.50 (9H, singlet);

of 1.95 (3H, singlet);

to 2.06 (3H, singlet);

of 2.09 (3H, singlet);

3,50 - of 3.80 (3H, multiplet);

of 3.80 (3H, singlet);

4,10 (1H, doublet of doublets, J = 1.0 and 10.5 Hz);
to 1.0 and 11.0 Hz);

and 5.30 (1H, multiplet);

of 5.83 (1H, doublet, J = 2.3 Hz);

of 6.20 (1H, doublet, J = 8,8 Hz).

30 (viii) Salt triperoxonane acid, 5-acetamido-4 - guanidino-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non - 2-topiramate acid

50 mg (0,076 mmol) of methyl 5-acetamido-4-( bis-t - butoxycarbonylamino)-8,9-di acetyl-2,3,4,5,7-pentadecane - 7-ethoxy glycero galacto-non-2-topiramate [obtained as described in stage (vii) above] dissolved in 2 ml of methanol, and the resulting solution was added 0.2 ml O 1 N methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture is neutralized 4M solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is dissolved in 1 ml of distilled water. Then 110 μl of 1N aqueous sodium hydroxide solution is added to the reaction mixture, which was then stirred at room temperaturea brand), and then water is removed by distillation. The resulting residue is purified column chromatography on silica gel using 5:1:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, getting 27 mg (75% yield) of the named compound as a colourless solid.

Rf = 0,30 (4:1:1 = isopropanol:acetic acid:water).

[]2D5= +32,5o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 361 (M++H).

1H-Spectrum nuclear magnetic resonance (D2O, 270 MHz) (ppm):

of 1.05 (3H, triplet, J = 7.0 Hz);

of 1.97 (3H, singlet);

3,40 (1H, multiplet);

3,50-the 3.65 (3H, multiplet);

of 3.80 (1H, doublet of doublets, J = 5.0 and 12 Hz);

are 3.90 (1H, multiplet);

to 4.15 (1H, doublet of doublets, J = 10 and 10 Hz);

4,40 - 4,50 (2H, multiplet);

of 5.55 (1H, doublet, J = 1,8 Hz).

EXAMPLE 31

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 199-38)

< / BR>
31 (i) Diphenylmethyl 5-acetamido-4-(N,N'- bis-t - butoxycarbonylamino)-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D - galacto-non-2-topiramate

495 mg (0.75 mmol) of methyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-8,9-di acetyl-2,3,4,5,7-Ute in 10 ml of methanol, and to the resulting solution add 2 ml of 0.1 N methanolic solution of sodium methoxide. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture is neutralized 4M solution of hydrogen chloride in dioxane, and the solvent is removed by distillation under reduced pressure. The resulting residue is dissolved in 10 ml of distilled water and there is added 1.0 ml of 1N aqueous sodium hydroxide solution. The mixture is then stirred at room temperature for 1 hour. At the end of this time the reaction mixture is neutralized 4M solution of hydrogen chloride in dioxane, and then water is removed by distillation. The resulting residue is dissolved in 6:1, by volume mixture of methanol and methylene chloride, and 500 mg (2,60 mmol) diphenyldiazomethane and 50 mg (0.38 mmol) of the complex of boron TRIFLUORIDE-diethyl ether is added to the resulting solution. The mixture is then stirred at room temperature for 2 hours, after which there is added acetic acid, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using a 20:1 by volume mixture of methylene chloride and methanol as eluent, receiving 450 mg (yield 82%) of n is SS="ptx2">

[]2D5= -10,7o(C = 0,13, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 727 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 1.20 (3H, triplet, J = 7.0 Hz);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

of 1.95 (3H, singlet);

3,60 - 4,10 (6H, multiplet);

4,30 - 4,50 (2H, multiplet);

5,10 (1H, multiplet);

5,95 (1H, doublet, J = 2.7 Hz);

6,55 (1H, doublet, J = 8.0 Hz);

to 6.95 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

and 8.50 (1H, doublet, J = 8.5 Hz).

31 (ii) Diphenylmethyl 5 - acetamido-4-(N,N'-bis-t-butoxycarbonylamino)-9-O-octanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2 - topiramate

30 mg level (0.041 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - ethoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 6 mg (0.06 mmol) of triethylamine and 8 mg (0.05 mmol) octanoyl chloride. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and organic is storytell removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50: 1, by volume mixture of methylene chloride and methanol as eluent, receiving 24 mg (yield 69%) of the named compound as a colorless amorphous substance.

Rf = 0,30 ( 20:1 = methylene chloride:methanol).

[]2D5= -14,0o(=0,05, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 854 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

of 1.20 (3H, triplet, J = 7.0 Hz);

1,20 - 1,30 (8H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

of 1.95 (3H, singlet);

of 2.33 (2H, triplet, J = 7.5 Hz);

3,50 (1H, triplet, J = 5.5 Hz);

3,59 (2H, Quartet, J = 7.0 Hz);

4,10 - 4,50 (5H, multiplet);

5,10 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,10 (1H, doublet, J = 8.7 Hz);

6,94 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

31 (iii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid

20 mg (0,023 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 octanoyl-2,3,4,5,7-pentad volume, a mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent to give 10 mg (yield 73%) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate-water).

[]2D5= +55o(C = 0,10, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 487 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

to 1.15 (3H, triplet, J = 7.0 Hz);

1,20 - 1,40 (8H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

3,45 - of 3.60 (3H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

EXAMPLE 32

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 199-40)

< / BR>
32 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-dodecanoyl-2,3,4,5,bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7-ethoxy glycero galacto-non-2-topiramate [received, as described in Example 31 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 6 mg (0.06 mmol) of triethylamine and 11 mg (0.05 mmol) dodecanoyl chloride. The mixture was stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 29 mg (yield 78%) of the named compound as a colorless amorphous substance.

Rf = 0.35 in (20:1 = methylene chloride:methanol).

[]2D5= -9,0o(s = 0,1, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 910 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

of 1.20 (3H, triplet, J = 7.0 Hz);

1,20 - 1,30 (16H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

1,95 (3H, si is ltiple);

5,10 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,10 (1H, doublet, J = 8.7 Hz);

6,94 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

32 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid

28 mg (0.03 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 dodecanoyl - 2,3,4,5,7-pentadecane-7-ethoxy glycero galacto - non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 12 mg (yield 61%) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +50o(=0,05, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 543 (M++H).

1H-Range nuclear m(16H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

3,45 - of 3.60 (3H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

EXAMPLE 33

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-deletion-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 199-41)

< / BR>
33(i) Diphenylmethyl 5-acetamido-4-(N, N'-bis-t - butoxycarbonylamino)-9-O-deletion-2,3,4,5,7-pentadecane-7 - ethoxy-D-glycero-D-galacto-non-2-topiramate

30 mg level (0.041 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - ethoxy glycero galacto-non-2-topiramate [obtained as described in Example 31 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 6 mg (0.06 mmol) of triethylamine and 12 mg (0.05 mmol) dodecanoyl chloride. The mixture was stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent delaytable 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 30 mg (yield 78%) of the named compound as a colorless amorphous substance.

Rf = 0.35 in ( 20:1 = methylene chloride:methanol).

[]2D5= -8,0o(s = 0,1, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 938 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

of 1.20 (3H, triplet, J = 7.0 Hz);

1,20 - 1,30 (20H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

of 1.95 (3H, singlet);

of 2.33 (2H, triplet, J = 7.5 Hz);

3,50 (1H, triplet, J = 5.5 Hz);

3,59 (2H, Quartet, J = 7.0 Hz);

4,10 - 4,50 (5H, multiplet);

5,10 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,10 (1H, doublet, J = 8.7 Hz);

6,94 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

33 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-deletion-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid

28 mg (0.03 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 deletion-2,3,4,5,7-pentadecane-7-ethoxy glycero galacto-non-2-topiramate [obtained as opiconsivia at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 13 mg (yield 74%) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +38,0o(=0,05, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 571 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

to 1.15 (3H, triplet, J = 7.0 Hz);

1,20 - 1,40 (20H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

3,45 - of 3.60 (3H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = l,8 Hz).

EXAMPLE 34

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 199-42)

< / BR>
34 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D-glycero-D-galacto-non-2-topiramate

30 mg level (0.041 mmol) diphenylmethyl 5-acetamido-4-what about, as described in Example 31 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 6 mg (0.06 mmol) of triethylamine and 14 mg (0.05 mmol) hexadecanoyl chloride. The mixture was stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 31 mg (yield 78%) of the named compound as a colorless amorphous substance.

Rf = 0.35 in (20:1 = methylene chloride:methanol).

[]2D5= -7,5o(s = 0,1, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 966 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

of 1.20 (3H, triplet, J = 7.0 Hz);

1,20 - 1,30 (24H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

1,95 (3H, multiplet);

5,10 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,10 (1H, doublet, J = 8.7 Hz);

6,94 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

34 (ii) Salt triperoxonane acid, 5-acetamido-4 - guanidino-9-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-ethoxy-D - glycero-D-galacto-non-2-topiramate acid

28 mg (0,029 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 hexadecanoyl-2,3,4,5,7-pentadecane-7-ethoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 12 mg (yield 58%) of the named compound as a colourless solid.

Rf = 0,3 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +30,0o(s = 0,1, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 599 (M++H).

1H-SGC);

1,20 - 1,40 (24H, multiplet);

1,55 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

of 2.35 (2H, triplet, J = 7.5 Hz);

3,45 - of 3.60 (3H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

EXAMPLE 35

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 163-38)

< / BR>
35 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-octanoyl-2,3,4,5,7-pentadecane-7-methoxy-D - glycero-D-galacto-non-2-topiramate

57 mg (0.08 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - methoxy glycero galacto-non-2-topiramate [obtained as described in Example 29 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 11 mg (0.10 mmol) of triethylamine and 16 mg (0.09 mmol) octanoyl chloride. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent Udall, using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 38 mg (yield 58%) of the named compound as a colorless amorphous substance.

Rf = 0,5 (10:1 = methylene chloride:methanol).

[]2D5= +2,7o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 839 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

1,20 - 1,30 (8H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

to 1.98 (3H, singlet);

of 2.33 (2H, triplet, J = 7.5 Hz);

3,40 (1H, multiplet);

of 3.48 (3H, singlet);

4,10 - 4,50 (5H, multiplet);

by 5.18 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,18 (1H, doublet, J = 8.7 Hz);

6,92 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

35 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-octanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid

31 mg (0,037 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 octanoyl - 2,3,4,5,7-pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3 to 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 15 mg (yield 69%) of the named compound as a colourless solid.

Rf = 0.34 in (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +38,2o(C = 0,11, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 473 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,25 - 1,40 (8H, multiplet);

1,60 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

is 2.37 (2H, triplet, J = 7.5 Hz);

to 3.38 (3H, singlet);

of 3.45 (1H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

EXAMPLE 36

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-decanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 163-39)

< / BR>
36 (i) Diphenylmethyl 5-acetamido-4- (N,N'-bis-t-butoxycarbonylamino)-9-O-decanoyl-2,3,4,5,7 - pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate

56 mg (0.08 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonyl 29 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 11 mg (0.10 mmol) of triethylamine and 18 mg (0.09 mmol) decanoyl chloride. The mixture was stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 40 mg (yield 50%) of the named compound as a colorless amorphous substance.

Rf = 0,5 (10:1 = methylene chloride:methanol).

[]2D5= +13,9o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 867 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

1,20 - 1,30 (12H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

to 1.98 (3H, singlet);

of 2.33 (2H, triplet, J = 7.5 Hz);

3,40 (1H, multiplet);

of 3.48 (3H, singlet);

4,10-uplet, J = 8.7 Hz);

6,92 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

36 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-decanoyl-2,3,4,5,7-pentadecane-7-methoxy-D - glycero-D-galacto-non-2-topiramate acid

33 mg (0.04 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 decanoyl-2,3,4,5,7 - pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in Example 36 (i)] is dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 20 mg (yield 85%) of the named compound as a colourless solid.

Rf = 0.34 in (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +33,3o(C = 0,11, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 501 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,25 - 1,40 (12H, multiplet);
tiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = l,8 Hz).

EXAMPLE 37

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 163-40)

< / BR>
37 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-dodecanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate

51 mg (0.07 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in Example 29 (i)] dissolved in 2 ml of methylene chloride, and to the obtained solution under cooling with ice, add 9 mg (0.09 mmol) of triethylamine and 19 mg (0.09 mmol) dodecanoyl chloride. The mixture was stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, the e colorless amorphous substance.

Rf = 0,6 (20:1 = methylene chloride:methanol).

[]2D5= +2,4o(C = 0,13, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 895 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

1,20 - 1,30 (16H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

to 1.98 (3H, singlet);

of 2.33 (2H, triplet, J = 7.5 Hz);

3,40 (1H, multiplet);

of 3.48 (3H, singlet);

4,10 - 4,50 (5H, multiplet);

by 5.18 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,18 (1H, doublet, J = 8.7 Hz);

6,92 (1H, singlet);

7,20 is 7.50 (10H, multiplet);

8,55 (1H, doublet, J = 8.7 Hz).

37 (ii) Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-dodecanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid

31 mg (0.035 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 dodecanoyl-2,3,4,5,7 - pentadecane-7-methoxy glycero galacto-non-2-topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time dissolve the e, using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 22 mg (yield 98%) of the named compound as a colourless solid.

Rf = 0.31 in (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +25,8o(C = 0,16, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 529 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,25 - 1,40 (16H, multiplet);

1,60 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

is 2.37 (2H, triplet, J = 7.5 Hz);

to 3.38 (3H, singlet;

of 3.45 (1H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

EXAMPLE 38

Salt triperoxonane acid, 5-acetamido-4-guanidino-9-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid (Compound N 163-42)

< / BR>
37 (i) Diphenylmethyl 5-acetamido-4-(N,N'-bis-t - butoxycarbonylamino)-9-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate

50 mg (0.07 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-2,3,4,5,7-pentadecane-7 - methoxy glycero galacto-non-2-topiramate [obtained as described in Example 29 (i)] dissolved in 2 ml matelec) hexadecanoyl chloride. The mixture is then stirred at 0oC for 1 hour. At the end of this time the reaction mixture was poured into a 2-layer solution of 5 ml of ethyl acetate and 3 ml of a saturated aqueous solution of acid sodium carbonate, and the organic layer was washed with saturated aqueous sodium chloride. Then dried over anhydrous sodium sulfate, and the solvent is removed by distillation under reduced pressure. The resulting residue is purified column chromatography on silica gel using 50:1, by volume mixture of methylene chloride and methanol as eluent, receiving 40 mg (yield 60%) of the named compound as a colorless amorphous substance.

Rf = 0,6 (10:1 = methylene chloride:methanol).

[]2D5= +5,5o(C = 0,11, CHCl3).

Mass spectrum (of the Belarusian library Association, FAB) m/z 951 (M++H).

1H-Spectrum nuclear magnetic resonance (CDCl3, 270 MHz) (ppm):

of 0.85 (3H, multiplet);

1,20 - 1,30 (24H, multiplet);

to 1.48 (9H, singlet);

of 1.50 (9H, singlet);

1,55 - 1,70 (2H, multiplet);

to 1.98 (3H, singlet);

of 2.33 (2H, triplet, J = 7.5 Hz);

3,40 (1H, multiplet);

of 3.48 (3H, singlet);

4,10 - 4,50 (5H, multiplet);

by 5.18 (1H, double doublet of doublets, J = 2,4, 9.0 and 9.0 Hz);

5,95 (1H, doublet, J = 2.3 Hz);

6,18 (1H, tuberiferous acid, 5-acetamido-4-guanidino-9-O-hexadecanoyl-2,3,4,5,7-pentadecane-7-methoxy-D-glycero-D-galacto-non-2-topiramate acid

34 mg (being 0.036 mmol) diphenylmethyl 5-acetamido-4 - bis-t-butoxycarbonylamino)-9 hexadecanoyl-2,3,4,5,7 - pentadecane-7-methoxy glycero galacto-non-2 - topiramate [obtained as described in stage (i) above] dissolved in 3 ml of 3:1 by volume mixture of methylene chloride and triperoxonane acid, and the mixture is stirred at room temperature for 5 hours. At the end of this time the solvent is removed by distillation under reduced pressure, and the residue is purified column chromatography on silica gel using 2:5:1 by volume mixture of isopropanol, ethyl acetate and water as eluent, receiving 23 mg (yield 92%) of the named compound as a colourless solid.

Rf = 0,47 (2:5:1 = isopropanol:ethyl acetate:water).

[]2D5= +21,6o(C = 0,12, CH3OH).

Mass spectrum (of the Belarusian library Association, FAB) m/z 585 (M++H).

1H-Spectrum nuclear magnetic resonance (CD3OD, 270 MHz) (ppm):

of 0.90 (3H, multiplet);

1,25 - 1,40 (24H, multiplet);

1,60 - 1,70 (2H, multiplet);

a 2.00 (3H, singlet);

is 2.37 (2H, triplet, J = 7.5 Hz);

to 3.38 (3H, singlet;

of 3.45 (1H, multiplet);

4,10 - and 4.40 (6H, multiplet);

of 5.53 (1H, doublet, J = 1,8 Hz).

Preparative example 1

Get water races 89,56% (weight) of purified water.

Preparative example 2

Receive an aqueous solution with a co-solvent containing 10% (weight) of the compound of example 1, a 0.04% (weight) of benzylaniline, 10,0% (weight) of polyethylene glycol 400, 30% (weight) of propylene glycol and 39,96% (weight) of purified water.

Preparative example 3

Get a dry powder containing 40% (weight) of the compound of example 1 and 60% (weight) of lactose.

Preparative example 4

Get an aerosol containing 10% (weight) of the compound of example 1, 0.5 percent (weight) of lecithin, 34.5% of Flon 11 and 55% of Flon 12.

1. Derivatives of neuraminic acid of the formula I

< / BR>
where R1represents an alkyl group having from 1 to 4 carbon atoms, or haloalkyl group having from 1 to 4 carbon atoms;

R2and R3are the same or different from each other and each represents a hydrogen atom or an aliphatic acyl group having from 2 to 25 carbon atoms;

X represents a hydroxy-group, halogen atom, alkoxygroup having from 1 to 4 carbon atoms, or a group of the formula RaO-, where Rarepresents an aliphatic acyl group having from 2 to 25 carbon atoms;

Y represents a group of formula RbRcN or RbRcN-O-, where Rb
Z represents an oxygen atom or a sulfur atom; provided that when Y represents an amino group and Z represents an oxygen atom, then X represents a halogen atom or alkoxygroup;

or their pharmaceutically acceptable salts or their esters.

2. Connection on p. 1, where R1is methyl or geometrinae group.

3. Connection on p. 1, where R1is a methyl group or a methyl group having at least one fluorine-Deputy.

4. Connection on p. 1, where R1is methyl, permatile or deformational group.

5. Connection on p. 1, where R1is a methyl group.

6. Connection on p. 1, where R2is a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms.

7. Connection on p. 1, where R2is a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms.

8. Connection on p. 1, where R2is a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms, and R3is an atom of water is oiley or Palmitoyl group.

10. Connection on p. 1, where R2is octanone, decanolide, dodecanoyl, myristoleic or Palmitoyl group and R3is a hydrogen atom.

11. Connection on p. 1, where R3is a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms.

12. Connection on p. 1, where R3is a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms.

13. Connection on p. 1, where R3is a hydrogen atom or octanone, decanolide, dodecanoyl, myristoleic or Palmitoyl group.

14. Connection on p. 1, where X represents a halogen atom or alkoxy group having from 1 to 4 carbon atoms.

15. Connection on p. 1, where X represents a fluorine atom, a methoxy group or ethoxypropan.

16. Connection on p. 1, where Y represents an amino group or a group of the formula

RbRcN-O-,

where Rband Rcsuch as defined under item 1.

17. Connection on p. 1, where Y represents an amino group or aminochrome.

18. Connection on p. 1, where Y represents an amino group.

19. Connection on p. 1, metallinou group, R2represents a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms, R3represents a hydrogen atom or an aliphatic carboxylic acyl group having from 6 to 25 carbon atoms, X represents a halogen atom or alkoxy group having from 1 to 4 carbon atoms, Y represents an amino group or a group of the formula RbRcN-O-, where Rband Rcsuch as defined above, and Z represents an oxygen atom.

21. Connection on p. 1, where R1represents a methyl group or a methyl group having at least one fluorine-Deputy, R2represents a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms, R3represents a hydrogen atom or an aliphatic carboxylic acyl group having from 8 to 16 carbon atoms, X represents a fluorine atom, methoxy group or ethoxypropan, Y represents an amino group or aminochrome and Z represents an oxygen atom.

22. Connection on p. 1, where R1represents a methyl group or a methyl group having at least one fluorine-Deputy, R2represents a hydrogen atom or aliphatic represent a fluorine atom, the methoxy group or ethoxypropan, Y represents an amino group or aminochrome and Z represents an oxygen atom.

23. Connection on p. 1, where R1represents methyl, formeterol or deformational group, R2is octanoyl, technology, dodecanoyl, meritorious or Palmitoyl group, R3represents a hydrogen atom or octanoyl, technology, dodecanoyl, meritorious or Palmitoyl group, X represents a fluorine atom, a methoxy group or ethoxypropan, Y represents an amino group and Z represents an oxygen atom.

24. Connection on p. 1, where R1represents a methyl group, R2is octanoyl, technology, dodecanoyl, meritorious or Palmitoyl group, R3represents a hydrogen atom, X represents a fluorine atom, a methoxy group or ethoxypropan, Y represents an amino group and Z represents an oxygen atom.

25. Connection on p. 1, which is:

5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-foreclosureatlanta-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-dodecanoyl-2,3,4,5,7-pentadecane-7-fterolaka-non-2-topiramate acid;

5-Aceto-4-guanidino-9-0-Palmitoyl-2,3,4,5,7-pentadecane-7-fterolaka-non-2-topiramate acid;

5-acetamido-4-guanidino-2,3,4,5,7-pentadecafluorooctanoate-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-myristoyl-2,3,4,5,7-pentadecane-7-metaxalone-non-2-topiramate acid;

5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-ethoxypyrrolidine-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-octanoyl-2,3,4,5,7-pentadecane-7-ethoxylate-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-dodecanoyl-2,3,4,5,7-pentadecane-7-ethoxylate-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-myristoyl-2,3,4,5,7-pentadecane-7-ethoxylate-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-Palmitoyl-2,3,4,5,7-pentadecane-7-ethoxylate-non-2-topiramate acid;

5-acetamido-4-guanidino-9-0-octanoyl-2,3,4,5,7-pentadione-7-methoxyaniline-2-topiramate acid;

5-acetamido-4-guanidino-9-0-decanoyl-2,3,4,5,7-pentadione-7-methoxy-D-glycero-D-galactose-2-topiramate acid;

5-acetamido-4-guanidino-9-0-dodecanoyl-2,3,4,5,7-pentadione-7-methoxy-D-glycero-D-galactose-2-topiramate acid and

5-acetamido-4-guanidino-9-0-hexadecanoyl-2,3,4,5,7-pentadione-7-methoxy-D-glycero-D-galactose-2-topiramate acid,1 - 25 with validateonparse activity.

27. Pharmaceutical composition having validateonparse activity, including derivative of neuraminic acid in a mixture with a pharmaceutically acceptable carrier or diluent, wherein the derivative of neuraminic acid represents at least one compound of formula I, or its pharmaceutically acceptable salt or ester according to any one of paragraphs.1 - 25.

Priority signs:

22.07.96 the compounds of formula I, where R1represents an alkyl group having from 1 to 4 carbon atoms, or haloalkyl group having from 1 to 4 carbon atoms; R2and R3are the same or different and represent each a hydrogen atom or an aliphatic acyl group having from 2 to 25 carbon atoms, X represents a hydroxy-group, a halogen atom or a group of the formula Ra0-, where Rarepresents an aliphatic acyl group having from 2 to 25 carbon atoms, Y represents a group of formula RbRcN or RbRcN-O-, where Rband Rcare the same or different from each other and each represents a hydrogen atom, and the group forms the m oxygen or sulfur atom, provided that when Y is amino group and Z represents an oxygen atom, then X represents a halogen atom, or pharmaceutically acceptable salts or esters, the connection on p. 25, which represents a 5-acetamido-4-guanidino-2,3,4,5,7-pentadecane-7-foreclosureatlanta-non-2-topiramate acid;

04.04.97 - with X representing alkoxygroup having from 1 to 4 carbon atoms, all connections on p. 25, except for the first and last four;

21.07.97 - when Y represents a group of the formula NRbRwithwhere Rband/or Rwithrepresent an alkyl group having from 1 to 4 carbon atoms, the latter four compounds on p. 25.

 

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The invention relates to medicine, for treatment of allergic and diatopically diseases of the eyes and nose
The invention relates to medicine, for treatment of allergic and diatopically diseases of the eyes and nose

The invention relates to vasoconstrictor /(benzodioxan, benzofuran and benzopyran)-alkylamino/-alkyl-substituted guanidine formula I, their pharmaceutically acceptable salts, or their stereochemical isomers, where X = O, CH2or a direct bond; R1= H, C1-C4alkyl, R2= H, C1-C6alkyl, C3-C6alkenyl, C3-C6quinil, R3= H, C1-C4alkyl; or R2and R1taken together, may form a bivalent radical of the formula/CH2/m-, where m = 4 or 5; or R1and R2taken together may form a bivalent radical of formula-CH=CH -, or the formula/CH2/n-, where n = 2, 3 or 4; or R3may indicate a relationship when R1and R2taken together form a bivalent radical of formula-CH=CH-CH= -, -CH= CH-N= or-CH=N-CH=; where one or two hydrogen atom substituted by a halogen atom, a C1-C6alkoxygroup, C1-C6the alkyl, CN, NH, mono - or di(C1-C6alkyl) amino group, aminocarbonyl, C1-C6alkylaminocarbonyl, R4-H or C1-C6-alkyl; Alk1denotes a divalent C1-C3-ascandilwy radical, A denotes dwuhvalentny a radical of the formula /, lk2represents C2-C15-alcander or C5-C7-cycloalkenyl, and each "R" represents 0, 1, 2, R7and R8each independently is H, a halogen atom, a C1-C6by alkyl, hydroxyl, C1-C6allyloxycarbonyl, C1-C6alkoxygroup, cyano, amino, C1-C6the alkyl, carboxyla, nitro or amino group, aminocarbonyl, C1-C6alkylcarboxylic or mono - or di-(C1-C6)alkylamino, provided that excluded /2-/ (2,3-dihydro-1,4-benzodioxin-2-yl)-methyl/-amino/-ethyl-guanidine
The invention relates to medicine, in particular pharmacology and the new burns and wound healing products

The invention relates to new benzododecinium the compounds containing pharmaceutical compositions, method of production thereof, and to a method for producing an intermediate product

FIELD: organic synthesis.

SUBSTANCE: invention provides compounds of general formula I:

, where R1 represents -CO-Ra, -SO2-Rb, or aryl optionally substituted by lower alkoxy, wherein Ra represents cycloalkyl, cycloalkyl(lower)alkyl, cycloalkyloxy, aryl, aryloxy, aryl(lower)alkyl, aryl(lower)alkoxy, aryloxy(lower)alkyl, aryl-S-(lower)alkyl, aryl(lower)alkenyl, provided that aryl group can be optionally substituted by halogen, lower alkyl, hydroxy, nitro, cyano, lower alkoxy, phenyl, CF3, cyano(lower)alkyl, lower alkyl-C(O)NH, lower alkyl-CO, and lower alkyl-S; heteroaryl, heteroaryl(lower)alkyl, or heteroaryl(lower)alkoxy, provided that heteroaryl group is 5- or 6-membered ring or bicyclic aromatic group constituted by two 5- or 6-membered rings including 1-3 heteroatoms selected from oxygen, nitrogen, and sulfur and that heteroaryl group can be optionally substituted by lower alkoxy; Rb represents aryl, aryl(lower)alkyl, or heteroaryl, aryl group optionally substituted by halogen, cyano, or lower alkyl-C(O)NH; R2 and R3 represent hydrogen atoms; R4 representshydrogen or lower alkyl; R5 represents hydrogen, lower alkyl, cycloalkyl, benzodioxyl, or aryl optionally substituted by lower alkyl, halogen, lower alkoxy, hydroxy, or (lower)alkyl-C(O)O; n is 1 or 2; and pharmaceutically acceptable salts thereof and/or pharmaceutically acceptable esters thereof. Invention also provides a pharmaceutical composition exhibiting inhibitory activity with regard to cysteine proteases of the cathepsin family, which composition comprises compound of formula I, pharmaceutically acceptable recipient, and/or adjuvant.

EFFECT: increased choice of cysteine protease inhibitors.

34 cl, 1 tbl, 13 ex

FIELD: organic chemistry, chemical technology, medicine, biochemistry, pharmacy.

SUBSTANCE: invention relates to new derivatives of sulfonamides of the formula (I) or their pharmaceutically acceptable salts wherein R1 means -OH or -NHOH; R2 means hydrogen atom; R3 means alkyl, alkoxyalkyl, arylalkyl, pyridylalkyl or morpholinylalkyl; A means piperidyl or tetrahydrofuranyl; n = 0; E means a covalent bond; (C1-C4)-alkylene, -C(=O)-, -C(=O)O- or -SO2-; X means hydrogen atom, alkyl, aryl, arylalkyl, alkoxyalkyl, morpholinyl or tetrahydropyranyl; each among G and G' means -C(R5)=C(R5') wherein R5 and R5' mean hydrogen atom; M means the group -CH-; z means the group -(CR7R7')a-L-R8 wherein a = 0 and each among R7 and R7' means hydrogen atom; L means a covalent bond; R8 means halogen atom or alkoxy-group. Compounds of the formula (I) are inhibitors of metalloproteases and can be used for treatment of arthritis, cancer tumors and other diseases.

EFFECT: valuable medicinal properties of compounds.

15 cl, 7 tbl, 56 ex

FIELD: medicine.

SUBSTANCE: before applying substitute hormonal therapy (SHT) on should evaluate antithrombogenic activity of vascular wall in women. For this purpose one should determine quantitative values of ADP-induced aggregation of thrombocytes, activity of antithrombin III in blood and fibrinolytic blood activity both before and after "cuff"-test. Then one should detect the indices calculated as the ratio of mentioned values both before and after carrying out the mentioned test. If mentioned indices are decreased against the norm by 20-40% women should be prescribed to undergo SHT at additional introduction of aspirin and supradin. The method provides prophylaxis of cardio-vascular diseases in this category of female patients due to correcting affected functional activity of vascular endothelium.

EFFECT: higher efficiency of prophylaxis.

1 cl, 1 ex, 4 tbl

FIELD: medicine, natural compounds.

SUBSTANCE: larch wood is saturated with water and extraction with ethyl acetate is carried out. Prepared extract is treated with hot water and this process is combined with distilling off a solvent. Then water-insoluble resin impurities are separated and crude product is isolated by crystallization and recrystallized. Invention provides simplifying the process.

EFFECT: improved preparing method.

2 ex

FIELD: medicine, pharmaceutical industry, pharmacy.

SUBSTANCE: invention relates to compositions used for treatment and/or prophylaxis of chlamydium infections caused by C. pheumoniae. Pharmaceutical composition used for treatment and/or prophylaxis of chlamydium infection caused by C. pneumoniae comprises the taken phenolic compound, or extract, or fraction, or incomplete fraction comprising the taken phenolic compound or corresponding synthetic compound, or mixture of indicated compounds obtained from plants. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction obtained from plants and comprising indicated compound or corresponding synthetic compound on C. pneumoniae represents the definite percent of inhibition for formation of inclusions. The composition useful for health eliciting an anti-chlamydium effect with respect to C. pneumoniae comprises the taken phenolic compound or extract, or fraction, or incomplete fraction containing indicated compound or corresponding synthetic compound, or mixture of indicated compounds obtained from plants. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound obtained from plants on C. pneumoniae represents the definite percent for inhibition in formation of inclusions. Also, invention relates to applying the composition useful for health in preparing foodstuffs or as supplements for nutrition for every day. Also, invention relates to applying phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound or mixture of indicated compounds obtained from plants in manufacturing a medicinal agent used for treatment and/or prophylaxis of chlamydium infections caused by C. pneumoniae. An anti-chlamydium effect of phenolic compound or extract, or fraction, or incomplete fraction comprising indicated compound or corresponding synthetic compound obtained from plants on C. pneumoniae represents the definite percent in inhibition in formation of inclusions. Compositions promote to effective prophylaxis and treatment of chlamydium infections caused by C. pneumoniae.

EFFECT: valuable medicinal properties of compounds.

21 cl, 1 dwg, 1 tbl, 6 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to new compounds of coumarone class, namely, to 6-nitro-2-iminocoumarin 3-carboxylic acid 4-toluidide silver salt of the formula (1): that elicits an antibacterial effect and can be used in medicine. Invention provides preparing a new compound eliciting an antibacterial effect with respect to S. aureus, E. coli, and C. albicans with mononuclear cells values 0.25; 0.5 and 7.8 mcg/ml, respectively, and with acute toxicity value LD50 for these compounds 2 460 ± 230 mg/kg.

EFFECT: valuable properties of compound.

1 cl, 1 tbl, 2 ex

FIELD: organic chemistry, medicine, pharmacology.

SUBSTANCE: invention relates to new derivatives of carbamic acid esters of the general formula (I):

and their pharmaceutically acceptable salts eliciting activity with respect to metabotropic glutamate receptors mGlu of group I that can be used for treatment of acute and/or chronic neurological disorders. In the general formula (I) R1 means hydrogen atom or (C1-C7)-alkyl; R2 and R2' mean independently of one another hydrogen atom, (C1-C7)-alkyl, (C1-C7)-alkoxy-group, halogen atom or trifluoromethyl; X means oxygen (O), sulfur (S) atom or two hydrogen atoms not forming a bridge; A1/A2 mean independently of one another phenyl or 6-membered heterocycle comprising 1 or 2 nitrogen atom; B represents group of the formula:

wherein R3 means (C1-C7)-alkyl and others; Y means -O-, -S- or a bond; Z means -O- or -S-; or B means 5-membered heterocyclic group of formulae: (a) , (b) , (c) or (d) . Also, invention relates to methods for preparing compounds and to a medicinal agent based on thereof.

EFFECT: improved preparing methods, valuable medicinal properties of compounds.

22 cl, 1 tbl, 2 sch, 78 ex

FIELD: medicine.

SUBSTANCE: the present innovation deals with phospholipid complexes of proanthocyanidine A2 and pharmaceutical compositions upon their basis as antiatherosclerotic agents, those for preventing and treating myocardial and cerebral infarction. Phospholipids of the above-mentioned complex should be preferably chosen out of lecithins, phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine. The innovation provides the preparation to treat the above-mentioned diseases due to decreasing the quantity and burden of atheromatous plaque, decreased obstruction of carotid arteries and decreased thickness of vascular walls.

EFFECT: higher efficiency of prophylaxis and therapy.

9 cl, 11 dwg, 6 ex, 2 tbl

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