Substituted aminoethylpiperazine and medicinal products based on them

 

(57) Abstract:

Substituted AMINOETHYLPIPERAZINE formula I, where R1, R2- H; R3- halogen or alkyl; A, R4- C1-7alkyl; n is 0 or 1; X represents N or CH; R5- C1-7alkyl or AG-C1-4alkyl; AG - phenyl, naphthyl, furyl or substituted with R7, R8and R9phenyl, or R5and R6together with the nitrogen atom to which they are bound, form a possibly substituted 5-, 6 - or 7-membered heterocycle (other designations, see p. 1 claims). The compounds of formula I are effective against bacteria Helicobacter, allowing their use as active substances in the treatment of diseases caused by these bacteria. 2 S. and 4 C. p. F.-ly, 1 Il., 1 PL.

The technical field to which the invention relates

The invention relates to compounds intended for use in the pharmaceutical industry as active ingredients for the manufacture of medicines.

Prior art

In the International application WO 92/12976 describes certain substituted 2-(pyridylmethyl-, respectively sulfinil)-benzimidazole, which have effective action is possible a number of diseases of the stomach.

Description of the invention

The subject invention are the compounds of formula I (see below), where

R1 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy, halogen, trifluoromethyl, fully or partly substituted by fluorine, C1-C4alkoxy, chloroformate or 2-chloro-1,1,2-triptoreline;

R2 denotes hydrogen or C1-C4alkyl;

R3 denotes halogen or C1-C4alkyl;

R4 represents C1-C7alkyl;

And represents C1-C7alkylen;

X represents N or CH and

n denotes the number 0, 1 or 2,

and where

R5 represents C1-C7alkyl, C3-C8cycloalkyl or Ar-C1-C4alkyl and

R6 represents C1-C7alkyl, C3-C8cycloalkyl or Ar-C1-C4alkyl, and

Ar denotes phenyl, furyl, naphthyl, tetrahydronaphthyl or substituted by R7, R8 and R9 phenyl,

or where

R5 and R6 together with the nitrogen atom to which they are linked, represent an unsubstituted or substituted 5-, 6 - or 7 - membered heterocycle selected from the group comprising pyrrolidine, piperidine, piperazine, morpholine, indoline, octahydro-1H-indole, 1,2,3,4-tetrahydroquinoline, 1,2,3,4-tetrahydroisoquinoline, degma identical or different substituents, selected from the group comprising C1-C4alkyl, C1-C4alkoxy, C1-C4alkoxy-C1-C4alkyl, C1-C4alkoxycarbonyl, C1-C4alkylcarboxylic, hydroxy-C1-C4alkyl, hydroxy and carboxy,

- substituted pyrolidine radical substituted by one, two or three identical or different substituents selected from the group comprising C1-C4alkyl, heme. di (C1-C4alkyl, C1-C4alkoxy, C1-C4alkoxy-C1-C4alkyl,

C1-C4alkoxycarbonyl, C1-C4alkylsulphonyl, C1-C4alkylsulphonyl-C1-C4alkyl,

hydroxy-C1-C4alkyl, dihydroxy-(C1-C4alkyl, di (C1-C4alkylamino, di-C1-C4alkylamino-C1-C4alkyl, pyrrolidino, piperidino, pyrrolidinyl-C1-C4alkyl, piperidinyl-C1-C4alkyl, carbarnoyl, di-C1-C4alkylaminocarbonyl, piperidinylcarbonyl, morpholinoethyl, phenyl, substituted by R7, R8 and R9 phenyl, phenyl-C1-C4alkyl, benzoyl, substituted by halogen benzoyl, formyl, carboxy, cyano, hydroxy, halogen, sulfo,

- substituted pieperazinove raustiala, selected from the group comprising C1-C4alkyl, C3-C7cycloalkyl, C3-C7cycloalkyl-C1-C4alkyl, C1-C4alkoxycarbonyl, C1-C4alkoxycarbonyl-C1-C4alkyl,

hydroxy-C1-C4alkyl, di (C1-C4alkylamino-C1-C4alkyl, halo,-C1-C4alkyl, carbarnoyl, phenyl, substituted by R7, R8 and R9 phenyl, phenyl-C1-C4alkyl, substituted phenyl residue on R7, R8 and R9 phenyl-C1-C4alkyl, naphthyl, benzhydryl and substituted with a halogen benzhydryl,

- substituted morpholinyl radical substituted by one or two identical or different C1-C4alkyl radicals;

- substituted indolin-1 silt radical in position 2 and/or 3 may be substituted by carboxyl group or by one or two identical or different C1-C4alkyl radical, and in the benzoin fragment may be substituted by one or two identical or different substituents selected from the group comprising C1-C4alkyl, halogen and nitro;

- substituted 1,2,3,4-tetrahydroquinoline radical substituted by one or two identical or different substituents selected from the group comprising C1o can be substituted by one or two identical or different substituents, selected from the group comprising C1-C4alkyl, carboxy, phenyl, substituted phenyl residue on R7, R8 and R9 phenyl or phenyl-C1-C4alkyl, and benzoic acid fragment may be substituted by one or two substituents selected from the group comprising hydroxy, C1-C4alkoxy and CI-C1-C4alkylamino;

and

R7 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy, C1-C4alkylsulphonyl, halogen, C1-C4alkylamino or nitro,

R8 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy, halogen or nitro, and

R9 denotes hydrogen or trifluoromethyl,

and salts of these compounds.

C1-C4alkyl represents a linear or branched alkyl radicals with 1-4 carbon atoms. As examples butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and methyl radicals.

C1-C4alkoxy is a radical containing along with the oxygen atom of one of the above C1-C4alkyl radicals. As examples metaxylene and ethoxyline radicals.

TEW or partially substituted by fluorine, C1-C4alkoxy includes, for example, 1,2,2-triptoreline, 2,2,3,3,3-pentafluoropropane, perforators and primarily 1,1,2,2 - tetrafluoroethoxy, triptoreline, 2,2,2-triptoreline, deformedarse.

C1-C7alkyl represents a linear or branched alkyl radicals with carbon atoms 1-7. As examples heptyl, hexyl, neopentyl, isopentyl, pentyl, butyl, isobutyl, sec-butyl, tert-butyl, propyl, isopropyl, ethyl and methyl.

C1-C7alkylene represents a linear or branched C1-C7alkylene radicals, such as methylene (-CH2-), ethylene (-CH2-CH2-), trimethylenebis (-CH2-CH2-CH2-), tetramethylene (-CH2-CH2-CH2-CH2-), 1,2-dimethylethylene [-CH(CH3)-], 1,1-dimethylethylene [-C(CH3)2-CH2-] , 2,2-dimethylethylene [-CH2-C(CH3)2] , isopropylidenebis (-C(CH3)2-] , 1-methylethanol [-CH(CH3)CH2-] , pentamethylenebis (-CH2-CH2-CH2-CH2-CH2-), hexamethylenebis (-CH2-CH2-CH2-CH2-CH2-CH2and heptamethylnonane (-CH2-CH2-CH2-CH2-C is Lowy, cyclobutylamine, cyclopentylamine, tsiklogeksilnogo, cycloheptylamine and cyclooctyl radicals.

Ar-C1-C4alkyl represents one of the above, substituted by Ar C1-C4alkyl radicals. As examples finitely, benzyl, 2-fulleylove (=furfuryl) and 1-naphthylmethyl radicals.

C1-C4alkoxy-C1-C4alkyl represents one of the above C1-C4alkyl radicals, substituted by one of the above C1-C4CNS radicals. As examples methoxymethyl, methoxyethylamine and biotoxicology radicals.

C1-C4alkoxycarbonyl represents a radical containing together with the carbonyl group of one of the above C1-C4CNS radicals. As examples methoxycarbonyl and ethoxycarbonyl radicals.

C1-C4alkylcarboxylic represents a radical containing along with carbonyloxy one of the above C1-C4alkyl radicals. As examples acetoxy.

Hydroxy-C1-C4the alkyl represented the Mer can be called hydroclimatology, 2-hydroxyethyloxy or 3 - hydroxypropionic radicals.

C1-C4alkylsulphonyl represents a radical containing together with the carbonyl group of one of the above C1-C4alkyl radicals. As an example of this is the acetyl radical.

C1-C4alkylsulphonyl-C1-C4alkyl represents one of the above C1-C4alkyl radicals, substituted by one of the above C1-C4alkylcarboxylic radicals. As examples 2-oxopropanoic radical (acetonyl) and 2-oxobutanoic radical.

Dihydroxy-C1C4alkyl represents one of the above C1-C4alkyl radicals, substituted by two hydroxyl groups. As example can be mentioned 1,2-dihydroxyethylene radical.

Di-C1-C4alkylamino represents an amino radical substituted with two identical or different C1-C4alkyl radicals among the above. As examples dimethylamino, diethylamino and diisopropylamino radicals.

Di-C1-C4alkylamino-C1-C4the alkyl pradh di-C1-C4alkylamino radicals. As examples dimethylaminomethylene, dimethylaminoethoxy and diethylaminoethylamine radicals.

Pyrrolidinyl-C1-C4alkyl and piperidinyl-C1-C4alkyl represents the above C1-C4alkyl radicals substituted on pyrrolidinyloxy, respectively piperidinyloxy radicals. As examples can be called 2-pyrrolidineethanol, 2-piperidinoethyl, piperidinomethyl and 2-(4-piperidine-4-yl)ethyl radicals.

Di-C1-C4alkylaminocarbonyl represents a radical containing together with the carbonyl group of one of the above di - C1-C4alkylamino. As examples dimethylcarbamoyl and diethylcarbamoyl radicals.

C3-C7cycloalkyl-C1-C4alkyl represents one of the above C1-C4alkyl radicals substituted on one of the above C3-C7cycloalkyl radicals. As examples cyclopropylmethoxy, cyclohexylmethoxy and cyclohexylethylamine radicals.

C1-C4alkoxycarbonyl-C1-C4alkyl is EN C1-C4alkoxycarbonyl radicals. As an example, you can call ethoxycarbonylmethylene radical.

Halo-C1-C4alkyl represents one of the above C1-C4alkyl radicals substituted on one of the aforementioned halogen atoms. As an example, can be called 3-chloropropionyl radical.

As substituted by R7, R8 and R9 phenyl radicals include radicals, such as 3,4-dihydroxy-, 3-hydroxy-4-methoxy-, 3,4-dimethoxy-, 2-methoxy-, 2-ethoxy-, 3-methoxy-, 4-methoxy-, 2-hydroxy, 3-hydroxy, 4-hydroxy-, 3,4-dihydroxy-, 4-acetyl, 4-fluoro-, 4-chloro-, 2-chloro-, 3-chloro-, 3,4-dichloro-, 3-trifluoromethyl-, 2-trifluoromethyl-, 2-methyl-, 3-methyl-, 4-methyl-, 2,3-dimethyl-, 2,4-dimethyl-, 3,4-dimethyl-, 2,5-dimethyl-, 4-nitro-, 2,6-dinitro-4 - trifluoromethyl - 5-chloro-2-methylaminophenol.

As substituted pyrrolidino radicals include radicals, such as, for example, 2-methoxypyridine, 2-ethoxycarbonylpyrimidine, 2-methylpyrrolidine, 2,5-dimethylpyrrole, 2-carboxypropyl, 4-hydroxy-2 - ethoxycarbonylpyrimidine, 4-hydroxy-2-ethoxycarbonylpyrimidine, 2-(2-hydroxyethyl)pyrrolidine, 4-hydroxy-2 - carboxypropyl, 2-hydroxyethylpyrrolidine, 3-hydroxyprop shall be such radicals, as, for example, 3-hydroxypiperidine, 2 - carboxypeptidase, 3-aminopiperidine, 4-[2-(4-piperidine-4-yl)ethyl] piperidine, 4-cyan-4-phenylpiperidine, 4,4-dihydroxypyridine, 2-n-propylpiperidine, 5-ethyl-2-methylpiperidine, 2-dimethylaminopyridine, 2-(2-pyrrolidinyl) piperidine, 4-benzyl-4-hydroxypiperidine, 4-formyl-4-phenylpiperidine, 4-hydroxymethyl-4-phenylpiperidine, 4-n-propylpiperidine, 4-(3-phenylpropyl)piperidine, 4-dimethylaminopyridine, 4-ethoxy-4 - phenylpiperidine, 4-hydroxy-4-(4-forfinal)piperidine, 2-(1 - hydroxy)benzylpiperidine, 2-(1-hydroxy)-4-chlorobenzaldehyde, 4-(1-pyrrolidinyl) piperidine, 4,4-dimethylpiperidine, 4-phenyl-4-propylacetamide, 2,6-dimethylpiperidin, 3-hydroxy-2,6-dihydroxypyridine, 2,6-di-(2-oxobutyl)piperidine, 4 - hydroxypiperidine, 4-hydroxy-4-phenylpiperidine, 4-(1 - oxopropyl)-4-phenylpiperidine, 4-(1-oxobutyl)-4-phenylpiperidine, 4-phenyl-4-propylenecarbonate, 4-phenyl-4-(1 - piperidinylcarbonyl)piperidine, 4-carbarnoyl-4-phenylpiperidine, 4-carbarnoyl-4-dimethylaminopyridine, 4-morpholinomethyl-4 - phenylpiperidine, 4-carbamoylbiphenyl, 4-[3-(4-piperidinyl)propyl] piperidine, 2-carboxy-5-hydroxypiperidine, 4-acetyl-4 - phenylpiperidine, 2-ethyl-2-methyl-piperidine, 4-etoxycarbonyl - 4-phenylpiperidine, 4-bromo-4-Roxithromycin, 4-(4-perbenzoic)piperidine, 2-(1,2-dihydroxyethyl)piperidine, 2-(2-dimethylaminoethyl)piperidine, 4-(2-dimethylaminoethyl)piperidine, 4-(2-diethylaminoethyl)piperidine, 4-(4-chlorobenzoyl)piperidine, 4-(2-butylacetyl)piperidine, 4-[2-(1-piperidinyl)ethyl] piperidine, 2,3-dicarboximide, 2,4-dicarboximide, 2,6-dicarboxamide, 4-sulfapyridine, 2-ethoxycarbonylpyrimidine, 2 methylpiperidin, 2,2,6,6 - tetramethylpiperidine, 4-hydroxy-2,2,6,6-tetramethylpiperidine, 4-amino-2,2,6,6-tetramethylpiperidine, 2,6-dimethylpiperidine, 2-hydroxyethylpiperazine, 2-ethylpiperidine, 2-(2-hydroxyethyl) piperidine, 3-diethylcarbamoyl, 3-ethoxycarbonylpyrimidine, 4-hydroxy-4-(4-chlorophenyl)piperidine, 4-(1-piperidinyl)piperidine and 4-benzylpiperidine.

As substituted piperazino radicals include radicals, such as, for example, 4-methylpiperazine, 4-[2-(2 - triptoreline)ethyl]-piperazine, 4-(3-chloropropyl)piperazine, 4-phenylpiperazine, 4-(2-were)-piperazine, 4-(2,3-dimetilfenil) piperazine, 4-(2-chlorophenyl)piperazine, 4-(2-methoxyphenyl) piperazine, 4-(2-ethoxyphenyl)piperazine, 4-(3-chlorophenyl)piperazine, 4-(4-forfinal)piperazine, 4-(4-chlorophenyl)piperazine, 4-(4-methoxyphenyl)piperazine, 4-carbamoylbiphenyl, 3-methyl-4-(4-chlorophenyl)piperazine, 3-methyl-4-(4 - meth is 4-(3,4 - dimetilfenil)piperazine, 4-(3-hydroxypropyl)piperazine, 3-methyl-4 - phenylpiperazin, 3-methyl-4-(3-chlorophenyl)piperazine, 4-benzylpiperazine, 4-propylpiperazine, 4-(3-were)piperazine, 4-(3-methoxyphenyl)piperazine, 4-(4-were)piperazine, 4-(2,5-dimetilfenil)piperazine, 4-benzhydrylpiperazine, 4-cyclopropylbenzene, 4-cyclobutylmethyl, 4-cyclopentylpropionyl, 4-cyclohexylpiperazine, 4-cycloheptylmethyl, 4-n-butylpiperazine, 4-isobutylpyrazine, 4-tert-butylpiperazine, 4-dimethylaminomethylphenol, 4-(2-diethylaminoethyl) piperazine, 4-(3-triptoreline)piperazine, 4-(1-phenylethyl) piperazine, 4-ethoxycarbonylmethylene, 4-(2-phenylethyl)piperazine, 4-(2-cyclohexylethyl)piperazine, 4-(2-dimethylaminoethyl)piperazine, 4-(2-hydroxyphenyl)piperazine, 4-(3,4-acid)piperazine, 4-isopropylpiperazine, 3-methyl-4-(3-methoxyphenyl)piperazine, 4-(4-hydroxyphenyl)piperazine, 3-methyl-4-(3-were) piperazine, 4-(3-hydroxyphenyl) piperazine, 4-(2,6-dinitro-4 - triptoreline)piperazine, 4-(1-naphthyl)piperazine, 4-(2-hydroxyethyl)piperazine, 4-(4-nitrophenyl)piperazine, 4-(4-acetylphenyl)piperazine, 4-ethoxycarbonylpyrimidine and 4-(4-chlorobenzhydryl) piperazine.

As substituted morpholino radical include, for example, 3,5-dimethylmorpholine radical.

As substituted 1,2,3,4-tetrahydroquinolines radicals can be called such, for example, as 2-etoxycarbonyl-1,2,3,4 - tetrahydro-1-chinoline, 2-methyl-1,2,3,4-tetrahydro-1-chinoline, 6-methyl-1,2,3,4-tetrahydro-1-chinoline, 6-fluoro-2-methyl-1,2,3,4 - tetrahydro-1-chinoline, 4-methyl-1,2,3,4-tetrahydro-1-chinoline, 8-amino-1,2,3,4-tetrahydro-1-chinoline and 2-fluoro-6-methyl-1,2,3,4 - tetrahydro-1-chinoline.

As substituted 1,2,3,4-tetrahydroisoquinolines radicals include radicals, such as, for example, 1-methyl-6,7 - dihydroxy-1,2,3,4-tetrahydro-2-ethenolysis, 1-(3,4 - dihydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydro-2-ethenolysis, 3-carboxy-1,2,3,4-tetrahydro-2-ethenolysis, 6,7-dimethoxy - 1,2,3,4-tetrahydro-2-ethenolysis, 1-benzyl-1,2,3,4-tetrahydro-2 - ethenolysis, 1-(3-hydroxy-4-methoxybenzyl)-6-dimethylamino - 1,2,3,4-tetrahydro-2-ethenolysis, 3-tert-butyl-6-methoxy-4-phenyl - 1,2,3,4-tetrahydro-2-ethenolysis, 1-(3,4-dimethoxybenzyl)-6,7 - dimethoxy-1,2,3,4-tetrahydro-2-ethenolysis, 1-(3,4 - dihydroxybenzyl)-6,7-dihydroxy-1,2,3,4-tetrahydro-2-ethenolysis, 6,7-dihydroxy-1,2,3,4-then it is carbonated shall thinline, 6-hydroxy-7-methoxy-1-methyl - 1,2,3,4-tetrahydro-2-ethenolysis and 1-(5-chloro-2-methylaminophenol)- 1,2,3,4-tetrahydro-2-ethenolysis.

As salts of the compounds of formula I in which n denotes the number 0 can be considered all of the acid additive salt. In the first place should be called a pharmacologically acceptable salt of inorganic and organic acids, which are usually used in Galenika. Pharmacologically unacceptable salts are formed, for example, upon receipt of the compounds according to the invention on an industrial scale as the primary products of the way, using well-known specialist methods are converted into pharmacologically acceptable salts. As such suitable water-soluble and water-insoluble acid additive salts, obtained by using such acids as hydrochloric acid, Hydrobromic acid, phosphoric acid, nitric acid, sulfuric acid, acetic acid, citric acid, D-Glukhova acid, benzoic acid, 2-(4-hydroxybenzoyl)-benzoic acid, butyric acid, sulfosalicylic acid, maleic acid, lauric acid, malic acid, fumaric acid, succinic acid, oxalic acid, tartaric acid, albanova kislota, moreover, acid upon receipt of salts, depending on whether one - or polybasic acid and depending on which salt is required to get used in equimolar or approximately equimolar proportions.

As compounds of the formula I in which n denotes the number 1 or 2, can also be seen salts, obtained by using reason. As examples of basic salts can be called a salt of lithium, sodium, potassium, calcium, aluminum, magnesium, titanium, ammonium, meglumine or guanidine, and in these cases the grounds upon receipt of salts used in equimolar or approximately equimolar proportions.

Among the compounds of formula I should highlight those in which R1 is hydrogen, R2 is hydrogen, R3 is halogen, and n denotes the number 0, and the salts of these compounds.

Especially worth mentioning are also the compounds of formula I in which R1 is hydrogen, R2 is hydrogen, R3 is chlorine, R4 is C1-C4the alkyl And represents ethylene or propylene, X represents CH and n denotes the number 0, and the salts of these compounds.

Among the resolved compounds of formula I, in which R1 denotes hydrogen, R2 denotes hydrogen, R3 denotes halogen, R4 represents C1-C4alkyl, And a represents C2-C4alkylene, X denotes N or CH, and n denotes the number 0, and where R5 represents a C1-C4alkyl or Ar-C1-C4alkyl and R6 represents Ar-C1-C4alkyl, and Ar denotes phenyl, furyl or substituted by R7, R8 and R9 phenyl, or where R5 and R6 together with the nitrogen atom to which they are linked, represent an unsubstituted or substituted 6-membered heterocycle selected from the group comprising piperidine, piperazine, 1,2,3,4-tetrahydroquinoline and 1,2,3,4-tetrahydroisoquinoline, and

- substituted piperidino radical substituted by one or two identical or different substituents selected from the group comprising C1-C4alkyl, C1-C4alkoxy, phenyl, substituted by R7, R8 and R9 phenyl and phenyl-C1-C4alkyl;

- substituted pieperazinove radical in position 4 is substituted by the Deputy selected from the group comprising C1-C4alkyl, C1-C4alkoxycarbonyl, phenyl, substituted by R7, R8 and R9 phenyl, phenyl-C1-C4alkyl, substituted by R7, R8 and R9 phenyl residue phenyl-C1-C4alkyl and benzhydryl what stitely, selected from the group comprising C1-C4alkyl and halogen;

- substituted 1,2,3,4-tetrahydroisoquinoline radical in benzoic fragment substituted by one or two substituents selected from the group comprising hydroxy, C1-C4alkoxy and CI-C1-C4alkylamino; and where the

R7 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy, halogen or nitro;

R8 denotes hydrogen, C1-C4alkyl, C1-C4alkoxy, halogen or nitro; and

R9 denotes hydrogen or trifluoromethyl;

and salts of these compounds.

Among the preferred compounds obtained according to one embodiment of the invention, special mention should be made of such compounds of formula I in which R1 denotes hydrogen, R2 denotes hydrogen, R3 represents chlorine, R4 represents C1-C4alkyl, And a represents ethylene or propylene, X is CH and n denotes the number 0, and where R5 represents a C1-C4alkyl or benzyl and R6 represents Ar-C1-C4alkyl, and Ar denotes phenyl or furyl, or where R5 and R6 together with the nitrogen atom to which they are linked, represent an unsubstituted or substituted 6-membered heterocycle selected from g is adical substituted Deputy selected from the group comprising phenyl and benzyl;

- substituted pieperazinove radical in position 4 is substituted by the Deputy selected from the group comprising phenyl, substituted by R7, R8 and R9 phenyl, and benzyl; and

- substituted 1,2,3,4-tetrahydroisoquinoline radical in benzoic acid fragment is substituted by one or two C1-C4CNS substituents; and where the

R7 denotes hydrogen or C1-C4alkoxy;

R8 denotes hydrogen and

R9 denotes hydrogen,

and salts of these compounds.

Another object of the invention is a method of obtaining compounds of formula I, where R1, R2, R3, R4, R5, R6, X, n and a have the above values, and their salts.

The method according to the invention differs in that a) mercaptobenzimidazole formula II (see attached sheet with formulas), where R1, R2 and X have the above meanings, is subjected to the interaction with picoline derivatives of the formula III (see attached sheet with formulas), where R3, R4, R5, R6 and a have the above values, a Y is a corresponding tsepliaeva group, or that

b) the compounds of formula IV (see attached sheet with formulas), where R1, R2, R3, R4, X, n and a have the above values, a Z is a corresponding tsepliaeva GRU the Wallpaper required end products) is then obtained according to a) or b) compounds with n = 0 oxidize and/or the compounds obtained, if necessary, transferred to salt and/or that the resulting salt if necessary, then transferred into the free compounds.

When carrying out the above described reaction between the parent compound can be used as such or, if necessary, in the form of their salts.

As mentioned above tseplyaesh groups Y, Z respectively include, for example, halogen atoms, especially chlorine, or alkylated by esterification (for example, using steam - toluensulfonate acid) hydroxyl group.

The interaction of compounds of the formula II with compounds of the formula III is carried out in a corresponding, preferably proton polar or aprotic solvents (such as methanol, ethanol, isopropanol, dimethylsulfoxide, acetone, dimethylformamide or acetonitrile) with the addition of water or completely in the absence of water. This interaction is carried out, for example, in the presence of a proton acceptor. As such suitable hydroxides of alkali metals such as sodium hydroxide, carbonates of alkali metals such as potassium carbonate, or tertiary amines, such as pyridine, triethylamine or ethyldiethanolamine. An alternative to this interaction can also be carried out without the use of a proton acceptor, and - depending on the type of the source compounds, if necessary, the manage from the 0oC to 150oC, and in the presence of a proton acceptor preferred temperature range lies in the range of 20oC to 80oC, and in the absence of acceptor of protons, the range is 60-120oC, is especially preferred when the boiling point of the used solvent. The duration of the reaction is from 0.5 h to 30 h

The interaction of compounds of the formula IV with amines H-N(R5)R6 carried out by the method similar to the reactions of compounds of the formula II with compounds of formula III, respectively, in an alternative embodiment, preferably without additives solvent using an excess of amine as an acceptor of protons and simultaneously as solvent. The temperature range in this case lies in the range of 60oC to 180oC, preferably from 80oC to 160oC.

The oxidation of sulfides (compounds of formula I with n=0) to sulfoxidov, respectively, to sulfones (compounds of formula I with n=1 or 2) is carried out in the reaction conditions, for which specialist oxidation of sulfides to sulfoxidov and sulfones obvious [see , for example, J. Drabowicz and M. Mikolajczyk, Organic preparations and procedures int. 14 (1-2), 45-89 (1982) or E. Block in S. Patai, The Chemistry of Functional Groups, Section E, Cho used for oxidation of sulfides to sulfoxidov and sulfones reagents, first of all, peroxyacids, such as peracetic acid, CRYPTOMAGAZINE acid, 4,5-dinitrosobenzene acid, nadalina acid, Monomeric-sifflet magnesium or preferably m-chlormadinone acid.

The temperature range of the reaction (depending on the reactivity of the oxidizing agent and the degree of dilution) is in the range from -70oC to the boiling point of the used solvent, preferably, however, -30oC to +20oC. Expedient was also to carry out the oxidation with Halogens, respectively, of hypogalactia (for example, using an aqueous solution of sodium hypochlorite), which is carried out in the temperature range of 0oC to 50oC. the Reaction is carried out, for example, in inert solvents, in particular in aromatic or chlorinated hydrocarbons, such as benzene, toluene, dichloromethane or chloroform, preferably in a complex or simple esters, such as ethyl ether, acetic acid, isopropyl ester of acetic acid or dioxane, or alcohols, preferably isopropanol.

The sulfoxidov according to the invention are optically active compounds. Depending on the type of substituents in the molecule, and their mixtures and racemates. Enantiomers can be separated by known methods (for example by preparation and separation of the respective diastereoisomeric compounds) (see, for example, International application WO 92/08716).

The compounds of formula II are known, for example from Germany application DE 3404610 or from the European patent 134400. The compounds of formula III can be obtained by the method described in the following examples or analogously to that described in European patent 184322.

The compounds of formula IV can be obtained, for example, by the method described in the examples below, from the known or derived in a similar way starting compounds.

Below the invention is explained more examples, which in no way limit its scope. Compounds according to the invention, as well as starting compound can be obtained according to the method similar to that described in the examples.

Examples

The final products

1. 2-{ 3-chloro-4-(N-[2-(N-benzyl-N-ethylamino)ethyl] -N - methylamino)-2-pyridyl} methylthio-1 N-benzimidazolethiol

2-{ 3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - pyridyl}methylthio-1H-benzimidazole (500 mg; 1,24 mmole) is heated in N-ethylbenzylamine (15 ml) to a temperature of 140oC and incubated tatoc chromatographic on silica gel (mixture of dichloromethane/methanol 97:3, containing 1 ml/l of concentrated aqueous solution of NH3). Collected pure fractions are concentrated together under vacuum, dissolved in a small amount of methanol, mixed with saturated dissolved in a simple ether hydrochloric acid (1 ml) and diisopropyl ether and precipitated in the precipitated solid is filtered off and dried under vacuum. Yield: 200 mg (28%) indicated in the title compounds as colorless solids with TPL> 180oC (decomposition).

2. 2-{ 3-chloro-4-(N-[2-(1.2.3.4-tetrahydroisoquinoline-2-yl)ethyl]-N-methylamino)-2-pyridyl}methylthio-1H - benzimidazolethiol

2-{ 3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - pyridyl}methylthio-1H-benzimidazole (500 mg) is heated in 1,2,3,4 - tetrahydroisoquinoline (10 ml) to a temperature of 100oC and maintain the temperature at this level for 2.5 hours the Excess amine is distilled off under high vacuum and the resulting oily residue chromatographic on silica gel (mixture of petroleum ether/ethyl acetate/methanol 65:30:5, containing 1 ml/l of concentrated aqueous solution of NH3). Collected pure fractions are concentrated together under vacuum, dissolved in a small amount of methanol (5 ml), mixed first with rastvoreno the precipitated solid is filtered off and dried under high vacuum. Yield: 460 mg (65%) indicated in the title compounds as colorless solids with TPL> 240oC (decomposition).

3. 2-13-chloro-4-{ N-[2-(1.2.3.4-tetrahydroisoquinoline-2 - yl)ethyl]-N-methylamino)-2-pyridyl}methylthio-1H-benzimidazole

2-{ 3-chloro-4-{ N-[2-(1,2,3,4-tetrahydroisoquinoline-2-yl)ethyl] -N-methylamino} -2-pyridyl)methylthio-1H-benzimidazolethiol (0.1 g) dissolved in water (7 ml) and mixed with a saturated solution of aqueous sodium bicarbonate (1 ml). Fallen in this colorless precipitate is filtered off, washed with distilled water and dried at a temperature of 60oC under high vacuum. Yield: 70 mg (87%) specified in the connection header with TPL> 88oC (decomposition).

4. 2-{3-methyl-4-{N-{2-[N-(2-furfuryl)-N-methylamino] ethyl}-N-methylamino} -2-pyridyl}methylthio-1H - benzimidazolethiol

Analogously to example 1 to obtain 1.35 g (64%) specified in the connection header with TPL212oC (decomposition) by the interaction of 2-{3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2-pyridyl} methylthio-1H - benzimidazole (1.5 g) with N-furfuryladenine (2 ml) after heating to 100oC and maintaining the temperature at this level for 4 hours

5. 2-{ 3-chloro-4-{N-[2-(1.2,3.4-tetrahydroisoquinoline-2-yl)ethyl]-N-methyl shall loretel)-N-methylamino] -2-pyridyl} methylthio-1H-imidazo [5,4-b] pyridine and 1,2,3,4-tetrahydroisoquinoline after chromatography on silica gel (ethyl acetate/methanol 4: 1) get mentioned in the title compound as a colourless powder with TPL128-129oC (52%).

6. 2-{ 3-chloro-4-{N-[2-(N-benzyl-N-methylamino)ethyl]-N - methylamino}-2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as amorphous powder with TPL237-240oC (decomposition) is obtained by interaction of 2-{ 3-chloro-4-[N-(2-chloroethyl)-N - methylamino] -2-pyridyl}methylthio-1H-benzimidazole N-methylbenzylamino after purification on silica gel and subsequent translation in trihydrochloride.

7. 2-{3-chloro-4-{N-[2-(N,N-dibenzylamino)ethyl]-N - methylamino}-2-pyridyl} methylthio-1H-benzimidazolethiol

According to the method described in example 2, indicated in the title compound as a colourless amorphous powder (obtained by grinding of cured oil) with uncertain TPLproduced by interaction of 2-{3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - pyridyl}methylthio-1H-benzimidazole with dibenzylamino after chromatography on silica gel (petroleum ether/ethyl acetate 1:1).

8. 2-{3-chloro-4-{N-[2-(N,N-diethylamino)ethyl]-N-methylamino} -2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as amorphous powder with TPL245,7oC (decomposition) floor which after chromatography on silica gel (ethyl acetate/methanol 4:1) and subsequent translation in trihydrochloride.

9. 2-{3-chloro-4-{N-[2-(N-methyl-N-phenethylamine)ethyl]-N - methylamino}-2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as amorphous powder with TPL239-241oC (decomposition) is obtained by interaction of 2-{ 3-chloro-4-[N-(2-chloroethyl)-N - methylamino] -2-pyridyl}methylthio-1H-benzimidazole N-methylphenethylamino after purification on silica gel (ethyl acetate/methanol 9:1) and subsequent translation in trihydrochloride.

10. 2-{3-chloro-4-{N-[2-(N-furfuryl-N-methylamino)ethyl]-N - methylamino]-2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as a brownish amorphous powder with TPL239-241oC (decomposition) is obtained by interaction of 2-{3-chloro-4-[N-(2 - chloroethyl)-N-methylamino]-2-pyridyl}methylthio-1H-benzimidazole N-furfuryladenine after chromatography on silica gel (ethyl acetate/methanol 9:1) and subsequent translation in trihydrochloride.

11. 2-{3-chloro-4-{N-[2-(4-phenylpiperidine)ethyl]-N - methylamino}-2-pyridyl} methylthio-1H-benzimidazole

According to the method described in example 2, indicated in the title compound as yellowish amorphous powder with TPL55-65oC get vzaimodeistvie on silica gel (ethyl acetate/methanol 3:1).

12. 2-{ 3-chloro-4-{ N-[2-(4-benzylpiperidine) ethyl]-N - methylamino}-2-pyridyl}methylthio-1H-benzimidazole

According to the method described in example 2, indicated in the title compound as a viscous yellowish oil is obtained by interaction of 2-{3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - pyridyl}methylthio-1H-benzimidazole with 4-benzylpiperidine after purification on silica gel (ethyl acetate/methanol 4:1).

13. 2-{3-chloro-4-[N-(2-piperidinoethyl)-N-methylamino]-2 - pyridyl}methylthio-1H-benzimidazole

According to the method described in example 2, indicated in the title compound as a viscous brown oil is obtained by interaction of 2-{3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - pyridyl} methylthio-1H-benzimidazole with piperidine after chromatography on silica gel (ethyl acetate/methanol 4:1).

14. 2-{ 3-chloro-4-{N-[2-(6,7-dimethoxy-1,2,3,4 - tetrahydroisoquinoline-2-yl)ethyl]-N-methylamino}-2-pyridyl} methylthio-1H-benzimidazole

According to the method described in example 2, indicated in the title compound as a viscous yellowish oil is obtained by interaction of 2-{3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - pyridyl} methylthio-1H-benzimidazole with 6,7-dimethoxy-1,2,3,4 - tetrahydroisoquinoline after chromatography on silica gel (ethyl acetate/methanol 4:1).

15. 2-{3-chloro-4-{N-[2-(Noah in example 1, specified in the title compound as amorphous powder with TPL212-215oC (decomposition) is obtained by interaction of 2-{ 3-chloro-4-[N-(2-chloroethyl)-N - methylamino] -2-pyridyl}methylthio-1H-benzimidazole with 4-phenylpiperazine after chromatography on silica gel (ethyl acetate/methanol 4:1) and subsequent conversion into the hydrochloride.

16. 2-{ 3-chloro-4-{N-[2-(4-benzylpiperazine)ethyl]-N - methylamino}-2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as amorphous powder with TPL227-230oC (decomposition) is obtained by interaction of 2-{ 3-chloro-4-[N-(2-chloroethyl)-N - methylamino] -2-pyridyl}methylthio-1H-benzimidazole with 4-benzylpiperazine after chromatography on silica gel (ethyl acetate/methanol 4:1)and subsequent translation in trihydrochloride.

17. 2-{3-chloro-4-{N-[2-(4-(2-methoxyphenyl)piperazine derivatives)ethyl]- N-methylamino} -2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as a viscous oil is obtained by interaction of 2-{3 - chloro-4-[N-(2-chloroethyl)-N-methylamino] -2-pyridyl} methylthio-1H - benzimidazole with 4-(2-methoxyphenyl)-piperazine after purification on silica gel (ethyl acetate/methanol 9:1).

18. 2 - {the Reid

Specified in the header of the connection with TPL239-240oC (decomposition) are obtained analogously to example 2 by reaction of 2-{3-chloro-4-[N-(3 - chloropropyl)-N-methylamino] -2-pyridyl} methylthio-1H-benzimidazole with 1,2,3,4-tetrahydroisoquinoline and translation in tetrahydrochloride.

19. 2-{3-chloro-4-{N-[3-(N-benzyl-N-methylamino)propyl]-N - methylamino}-2-pyridyl}methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as amorphous powder with TPL228-230oC (decomposition) is obtained by interaction of 2-{ 3-chloro-4-[N-(3-chloropropyl)-N - methylamino] -2-pyridyl}methylthio-1H-benzimidazole N-methylbenzylamino after purification on silica gel and subsequent translation in tetrahydrochloride.

20. 2-{ 3-chloro-4-{N-[3-(6.7-dimethoxy-1.2.3.4 - tetrahydroisoquinoline-2-yl)propyl]-N-methylamino}-2-pyridyl} methylthio-1H-benzimidazolethiol

According to the method described in example 1, indicated in the title compound as a viscous yellowish oil is obtained by interaction of 2-{3-chloro-4-[N-(3-chloropropyl)-N-methylamino] -2 - pyridyl}methylthio-1H-benzimidazole with 6,7-dimethoxy-1,2,3,4 - tetrahydroisoquinoline after chromatography on silica gel (petroleum ether/ethyl acetate/methanol 2:5:1).

21. 2-{ 3-chloro what the IR, described in example 1, indicated in the title compound as a viscous yellowish oil is obtained by interaction of 2-{3-chloro-4-[N-(3-chloropropyl)-N-methylamino] -2 - pyridyl}methylthio-1H-benzimidazole with 4-benzylpiperidine after purification on silica gel (ethyl acetate/methanol 4:1)and translated in trihydrochloride.

The preliminary stage

A. 2-{3-chloro-4-[N-(2-chloroethyl)-N-methylamino]-2 - pyridyl}methylthio-1H-benzimidazolethiol

1) 3-chloro-4-[N-(2-hydroxyethyl)-N-methylamino]-2 - hydroxymethylpropane

A mixture of 3,4-dichloro-2-hydroxymethylpropane (see Journ. Med. Chem. 1989, 32 , 1970) (2.5 g) in 2-methylaminoethanol (30 ml) is heated in a steel autoclave to 160oC and maintain the temperature at this level for 2.5 h, then the excess amine is removed under high vacuum and the resulting residue chromatographic on silica gel (dichloromethane/methanol 95:5). Yield: 2.3 g in the form of a yellowish oil.

2) 3-chloro-4-[N-(2-chloroethyl)-N-methylamino]-2 - chloromethylpyridine

A solution of 3-chloro-4-[N-(2-hydroxyethyl)-N-methylamino] -2 - hydroxymethylpropane (2.3 g) in dichloromethane (30 ml) is mixed by adding dropwise, at a temperature of 0oC with a solution of thionyl chloride (4 ml) in dichloromethane (20 ml). After raising (within 20 min) tempera is storytale the resulting residue chromatographic on silica gel (mixture of petroleum ether/ethyl acetate 7:3, containing 1 ml/l of concentrated aqueous solution of NH3). Output: 2,6,

3) a Mixture of 2-mercapto-1H-benzimidazole (1.8 g) and 3-chloro-4-[N- (2-chloroethyl)-N-methylamino]-2-chloromethylpyridine (1.1 g) in isopropanol (40 ml) was incubated for 1.5 h at boiling, after which the solvent is removed under vacuum to a volume of 20 ml and this solution is mixed with diisopropyl ether (20 ml). Drop down after some time, the crystals are filtered and dried under vacuum. Yield: 1.2 g specified in the connection header with TPL202oC (decomposition).

Similarly receive 2-{3-chloro-4-[N-(3-chloropropyl)-N - methylamino] -2-pyridyl} methylthio-1H-benzimidazolethiol

B. 2-{ 3-chloro-4-[N-(2-chloroethyl)-N-methylamino]-2 - pyridyl}methylthio-1H-imidazo[5,4-b]pyridine

A mixture of 3-chloro-4-[N-(2-chloroethyl)-N-methylamino] -2 - chloroethylnitrosourea (0.96 g(2-mercapto-1H-imidazo [5,4-b]pyridine (0.5 g) in isopropanol (25 ml) is heated to 90oC and maintain the temperature at this level for 4 h, after which the reaction mixture is cooled to 0oC. the Precipitated crystals are filtered and washed with a small amount of isopropanol. The cake is dissolved in water (30 ml), the solution is mixed with saturated aqueous HH vacuum and the resulting crystalline residue is dried under high vacuum. Yield: 0.68 g specified in the connection header with TPL184-185oC.

Industrial applicability

High efficiency of the compounds of formula I and their salts against bacteria Helicobacter allows them to be used in medicine as active substances for the treatment of diseases caused by these bacteria.

Another object of the invention, accordingly, is a method of treatment of mammalian, especially human, affected by the disease, which is caused by the bacteria Helicobacter. Proposed according to the invention the method is characterized by the fact that the afflicted individual is injected with a therapeutic effect and a pharmacologically acceptable amount of one or more compounds of the formula I and/or their pharmacologically acceptable salts.

The subject of the invention is, further, the compounds of formula I and their pharmacologically acceptable salts for use in the treatment of diseases caused by bacteria Helicobacter.

The invention also includes the use of compounds of the formula I and their pharmacologically acceptable salts for the manufacture of drugs to combat diseases caused by bacteria Helicobacter.

Among strains of the bacteria Helicobacter, against which the compounds of formula I possess effective anti-bacterial action in the first place should be called the strain of Helicobacter pylori.

Medications manufactured using methods obvious to the person skilled in the art. Used as drugs pharmacologically effective compounds of formula I and their salts (i.e., active ingredients) used either as such or preferably in combination with appropriate pharmaceutical excipients, for example, in the form of tablets, pills, capsules, emulsions, suspensions, gels or solutions, and content of active substances in them is preferably from 0.1 to 95%.

The choice of auxiliary substances for the preparation of the required compositions of medicines is determined by the person skilled in the art to which this choice is obvious. Besides solvents, gel-forming substances, excipients for tablets and other carriers of active substances can be used, for example, teamstudio solubility, dyes or activators permeability and complexing agents (e.g. cyclodextrins).

The active substances may be administered, for example, for parenteral administration (e.g. intravenous) or primarily for oral administration. In medicine, as a rule, the daily dose of injected active ingredients is from about 0.2 to 50, preferably from 1 to 30 mg/kg body weight; if necessary to achieve the desired effect, the daily dose can be divided into several, preferably 2-6, single doses.

In this connection, you must specify the following significant for the invention factor: compounds of formula I in which n denotes the number 0, to provide the desired effect against the bacteria Helicobacter even at a dose lower than doses that would need to be assigned to achieve a satisfying therapeutic targets inhibitory effect of the secretion of gastric acid.

The compounds of formula I in which n denotes the number 1, along with antibacterial efficacy against Helicobacter also have a pronounced inhibitory action to the secretion of acid gastric juice. In accordance with the above-mentioned seeding juice.

Biological studies

The compounds of formula I were tested for their efficacy against bacteria Helicobacter pylori according to the method described Tomoyuki lwahi and others (see Antimicrobial Agents and Chemotherapy, 1991, 490-496), using Columbia agar (oxoid) and with a growth period of 4 days. For the studied compounds were obtained with it are presented in the table below the minimal inhibitory concentration (MIC) (the numbers of the compounds correspond to the numbers of the compounds in the description).

1. Substituted AMINOETHYLPIPERAZINE General formula I

< / BR>
where R1is hydrogen;

R2is hydrogen;

R3- halogen or C1-C4-alkyl;

R4- C1-C7-alkyl;

A - C1-C7-alkylen;

n is 0 or 1;

X is N or CH;

R5- C1-C7-alkyl or Ar - C1-C4-alkyl;

R6- C1-C7-alkyl or Ar - C1-C4-alkyl, and Ar denotes phenyl, naphthyl, furyl or substituted with R7, R8and R9phenyl, or R5and R6both together with the nitrogen atom to which they are linked, represent an unsubstituted or substituted 5-, 6 - or 7-membered heterocycle selected from the group comprising pyrrolidine, piperidine, rezinovy radical may be substituted C1-C4-alkyl, phenyl or benzyl, pieperazinove radical may be substituted in position 4 of the phenyl, phenyl, substituted C1-C4-alkoxy, or benzyl, 1,2,3,4-tetrahydroisoquinoline radical can be substituted in the benzene fragment of one or two C1-C4-alkoxygroup;

R7is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkylsulphonyl, halogen, C1-C4-alkylamino or nitro;

R8is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, halogen or nitro;

R9is hydrogen or trifluoromethyl,

or their salts.

2. The compounds of formula 1 under item 1, in which R1denotes hydrogen, R2is hydrogen, R3- halogen, n = 0, or their salts.

3. The compounds of formula 1 under item 1, in which R1denotes hydrogen, R2is hydrogen, R3is chlorine, R4- C1-C4-alkyl, A denotes an ethylene or propylene, X is CH, n = 0, or their salts.

4. The compounds of formula 1 under item 1, in which R1denotes hydrogen, R2is hydrogen, R3- halogen, R4- C1-C4-alkyl, A - C2-C4-alkylene, X Is N or CH, n = 0, R5- C1-C4-alkyl or Ar-C1-C4-UB>, R8and R9phenyl, or R5and R6both together with the nitrogen atom to which they are linked, represent an unsubstituted or substituted 6-membered heterocycle selected from the group comprising piperidine, piperazine, 1,2,3,4-tetrahydroquinolin, and substituted piperidino radical substituted C1-C4-alkyl, phenyl or benzyl, substituted pieperazinove radical substituted in position 4 of the phenyl, phenyl, substituted C1-C4-alkoxy, or benzyl, 1,2,3,4-tetrahydroisoquinoline radical substituted in the benzene fragment of one or two C1-C4-alkoxygroup, R7is hydrogen, C1-C4-alkyl, C1-C4-alkoxy, halogen or nitro; R8is hydrogen, C1-C4-alkyl and C1-C4-alkoxy, halogen or nitro; R9is hydrogen or trifluoromethyl, or their salts.

5. The compounds of formula 1 under item 1, in which R1denotes hydrogen, R2is hydrogen, R3is chlorine, R4- C1-C4-alkyl, A is ethylene or propylene, X is CH, n = 0, R5represents a C1-C4-alkyl or benzyl and R6is an Ar-C1-C4-alkyl, and Ar denotes phenyl or furyl, or R5and R6both together with the nitrogen atom, with kotucha piperidine, piperazine and 1,2,3,4-tetrahydroquinolin, and substituted piperidino radical substituted by a Deputy selected from the group comprising phenyl and benzyl; substituted pieperazinove radical in position 4 is substituted by the Deputy selected from the group comprising phenyl, substituted with R7, R8and R9phenyl and benzyl; and substituted 1,2,3,4-tetrahydroisoquinoline radical in benzene fragment substituted by one or two C1-C4-CNS substituents and where R7is hydrogen or C1-C4-alkoxy; R8is hydrogen, R9hydrogen, or their salts.

6. The drug, designed to combat diseases caused by bacteria Helicobacter, including an active ingredient and pharmaceutically acceptable additives, wherein as the active ingredient use of compounds of formula 1 on p. 1.

 

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