UA72813C2 - Benzimidazole derivatives, preparation thereof and therapeutic application - Google Patents

Abstract

The invention concerns benzimidazole derivatives of general formula (I) wherein: X represents a nitrogen atom or a carbon atom, and when X represents a nitrogen atom: R3 represents a hydrogen atom or a C1-C4 alkyl group, or does not exist to produce compounds of formula (I) comprising a secondary or tertiary amine; R4 represents a hydrogen atom or a C1-C6 alkyi, C3-C7 cycloalkyl, C3-C7 heterocycloalkyl group optionally substituted, -(CH2)p-heteroaryl, heteroarylcarbonyl, phenylcarbonyl, C1-C6 alkylcarbonyl, -(CH2)pCOOR, phenylsulphonyl group optionally substituted; and when X represents a carbon atom: R3 represents a hydrogen atom or a -NR5R6, -N(R5)3+, -NHCOR7, -CONHR5, -COR7, -NHCONH2, -OH or CH2OH group, R4 represents a hydrogen atom or a -(CH2)p-phenyl group optionally substituted, -(CH2)p-heteroaryl or-(CH2)tNR7R8 group. The invention is useful in therapeutics for preparing a medicine for preventing or treating disorders wherein the poly(ADP-ribose) polymerase

Description

Description of the invention

The invention relates to benzimidazole derivatives, their preparation and use in therapy. The invention relates to 2 compounds of formula (1):

M Z () tk Z-6 Same

MO Cho 70 oh Not where:

K1 - a hydrogen atom, a C1-C4-alkyl group, a halogen atom, a nitro group or a C1-C4-alkyl group,

K2 and Kk2 are independently of each other a hydrogen atom or a C1-C4 alkyl group,

X is a nitrogen atom or a carbon atom, n is 1 or 2, t is 1 or 2, and when X is a nitrogen atom, then:

KZ is a hydrogen atom or a C1-C4 alkyl group, and then the compounds of formula (I) comprise a quaternary ammonium, or, alternatively, KZ is absent, and then the compounds of formula (I) comprise a secondary or tertiary amine,

KA - hydrogen atom,

C1-Cb-alkyl group,

C3-C7-cycloalkyl group, p

The C3-C7-heterocycloalkyl group, as an option, is substituted by a C1-C4-alkyl group or a -SOOK group, in which K o is a C1-C6-alkyl group, a group - (CHNo)p-heteroaryl, in which p can have a value from 0 to 4, and the heteroaryl group is selected from pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl, pyridizanyl, imidazolyl, and thienyl groups, and said heteroaryl group can optionally be substituted with a C1-C4 alkyl group, a heteroarylcarbonyl group, and the heteroaryl group is selected among the furyl, pyridyl, - pyrimidyl, pyrazinyl, pyridizinyl and imidazolyl groups, the phenylcarbonyl group, and the phenyl group, as an option, is replaced by a halogen atom, (ee) (C1-Cb)-alkylcarbonyl group, the "СНо)рСООК group, where p can have a value from 0 to 4, and K is a C1-C6-alkyl group, cm is a phenylsulfonyl group, as an option, substituted on the phenyl nucleus by a halogen atom, a trifluoromethyl group, a C1-C4-alkyl group, a nitro group or a C1-C4-alkyl group, or, in other In another embodiment, (CHNo)p-phenyl group, where p can be from 0 to 4, and the phenyl group is optionally substituted in the ortho-mMa or meta- and/or para position by one to three groups independently selected from "

C1-C4-alkyl, nitro-, amino-, hydroxyl group, halogen atom, trifluoromethyl group,

C1-C4-alkyl group, (C1-C4)-alkylphenyl group, C1-C4-alkylamino group, C1-C4-dialkylamino group, - c group -MHCNO or group -MHCOV', where B/ - (31-C4-alkyl or C1-C4-alkyl group, and this C1-C4-alkyl group, as an option, is replaced by a dimethylamino group, -» and, when X is a carbon atom, then:

KZ - hydrogen atom, group -ME"5Ev, group -M(K5)57, group -CHINSOK?7, group -SOMNE5, group -SOK?7, -MNSOMN" group, group "OH or group -SNOHON, - K4 - a hydrogen atom, co -(CH»)p-phenyl group, in which p can have a value from 0 to 4, and the phenyl group, as an option, is replaced by 1-3 groups selected, independently of each other, from C1-C4 - an alkyl group, a nitro group, an amino group, a halogen atom, a trifluoromethyl group or a C1-C4-apoxyl group, -о 70 -(СНо)р-heteroaryl group, in which P can have a value from 0 to 4, and the heteroaryl group is selected from an imidazolyl group, optionally substituted with a C1-C4 alkyl group, a pyridyl, aminopyridyl, c»pyrimidinyl, pyrazinyl or pyridazinyl group, or, alternatively, a -SNOHMK7KV group in which is 0 or 1, provided that when KA is the group -МК7КВ, then КЗ is not any of the groups -МК5Кб, -МНСОК?7, -МНСОМН» and -ОН, 99 К5 and Кб are, independently of each other, a hydrogen atom or a C1-C4-alkyl group,

HF) K?7 and K8 are, independently of each other, a C1-C4-alkyl or C1-C4-alkyl group, or together form a saturated 5-7-membered ring, which, as an option, includes an additional nitrogen atom to form , for example, where a 1-piperidyl, 1-pyrrolidinyl or 1-piperazinyl group, and this ring is on a carbon or nitrogen atom, including that hydrogen atom to which groups K?7 and K8 are attached to form quaternary ammonium, 60 as an option, can be replaced by a C1-C4-alkyl group or a group-SOOK", in which ВK" is a phenyl or (C1-C4)-alkylphenyl group, except for two compounds in which КИ, К2, К2, КЗ are H, X - C, n -t-1, and KA - 4-imidazolyl or 5-methyl-4-imidazolyl group.

These two compounds are described in the application EP 646 583 as compounds 16 and 17 in the table and ligands of the serotonergic receptor type 5-HT» and 5-HT,. because the compounds of formula (I) may include one or more asymmetric carbon atoms. Therefore, they can exist in the form of enantiomers or diastereomers. These enantiomers and diastereomers, as well as their mixtures, are included in the scope of the invention. The compounds of the invention can be bases or addition salts of pharmaceutically acceptable acids. Such salts are also included in the scope of the invention.

The following terms are used in this document: "(Ca-Cg)-alkyl group" - a linear or branched saturated aliphatic group containing from 4 to g carbon atoms (d and g o - whole), in particular, metallic, ethyl, propyl, isopropyl, n-propyl, butyl, isobutyl, tert-butyl, p-butyl, pentyl, etc. groups; "halogen atom" means fluorine, chlorine, bromine or

Id; 70 "C3-C7-cycloalkyl group" - a cyclic alkyl group containing from 3 to 7 carbon atoms, in particular, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl groups; "C3-C7-heterocycloalkyl group" - a cyclic alkyl group that contains from C to 7 carbon atoms and one or more heteroatoms, for example, nitrogen atoms, in particular it can be a piperidinyl group; "(C1-C4)alkoxyphenyl group" is a group of the formula -O-(CH2)y-phenyl, where x can have a value from 1 to 4.

Among the compounds of formula (1) according to the invention, those in which:

K1 - hydrogen atom, C1-C4-alkyl group or C1-C4-alkyl group,

KO - a hydrogen atom or a C1-C4 alkyl group,

K2 - hydrogen atom,

X is a nitrogen atom, n is 1 or 2, t is 1 or 2,

KZ is a hydrogen atom, and then the compounds of formula (I) comprise a quaternary ammonium, or alternatively, KZ is absent, and then the compounds of formula (I) comprise a secondary or tertiary amine,

KA - hydrogen atom,

C1-Cb-alkyl group,

C3-C7-cycloalkyl group, i) pyridyl, pyrimidinyl or pyrazinyl group, optionally substituted by C1-C4-alkyl group, heteroarylcarbonyl group, where the heteroaryl group is a furyl or pyridyl group, phenylcarbonyl group, where the phenyl group is optionally substituted by a halogen atom, c zo (C1-Cb)alkylcarbonyl group, ""CNo)pSOOK group, in which p is hapde ytot 0, 4, and K is a C1-Cb-alkyl group, -- phenylsulfonyl group, co-phenyl group, substituted 1-3 groups selected, independently of each other, from C1-C4-alkyl group, nitro group, amino group, hydroxyl group, halogen atom, trifluoromethyl group, C1-C4-alkyl c group, (C1-C4)-alkoxyphenyl group, (C1-C4)-dialkylamino group, group -MNONO or group -MNSORB", in which B! - - C1-C4-alkyl or C1-C4-alkyl group, and this C1-C4-alkyl group, as an option, is replaced by a dimethylamino group , -(CH»)p-phenyl group, in which P can have a value from 0 to 4, « -(CH»)p-pyridyl group, in which P can have a value of i from 0 to 4, -(CH2o)p-thienyl group, in which P can have a value from 0 to 4, - c (C3-C7)-heterocycloalkyl group, optionally substituted by a C1-C4-alkyl group or a group - SOOK, in which c Kk is a C1-Cb-alkyl group, "» or, in another version, compounds in which:

K1 - hydrogen atom,

K2 and kg are, independently of each other, a hydrogen atom or a C1-C4 alkyl group, -I X - a carbon atom, n equals 1 or 2, o t equals 1, (ee) KZ - a hydrogen atom, group -MA5Kb, group -M(K5)57, group -MNSOK?7, group -SOMNE5, group -MNSOMN", group shu 20 -OH or group -SHOOH,

KA is a hydrogen atom, this is a benzyl group (namely, -"(CH»o)p-phenyl group, in which p is 1), the phenyl group, as an option, is replaced by 1-3 groups, selected independently of each other, among

C1-C4 alkyl group, nitro group, amino group, halogen atom, trifluoromethyl group or

C1-C4-alkyl group, about | a heteroaryl group, namely, an imidazolyl group, optionally substituted by a C1-C4 alkyl group, or a pyridyl group, i.e.) a group -ME 728, provided that when KA is a group -МК7К8, then КЗ is not one of the groups -МК5Кб, -МНСОК?7, -МНСОМН 5 and -ОН, 60 К5 and Кб are, independently of each other, a hydrogen atom or a C1-C4-alkyl group,

K?7 and K8 are, independently of each other, a C1-C4-alkyl or a C1-C4-alkyl group, or together they form a saturated 5-7-membered ring, which, as an option, includes an additional nitrogen atom, and on the atom carbon or nitrogen atom, including that nitrogen atom to which K7 and K8 groups are attached to form quaternary ammonium, may optionally be substituted by a C1-C4 alkyl group or a -SOOK" group in which K" is phenyl or 65 ( "C1-C4)-alkylphenyl group, with the exception of two compounds in which КИ, К2, К2, КЗ are H, Х - C, п-т-1, and К4 - either 4-imidazolyl or 5-methyl-4 -imidazolyl group.

Among these preferred compounds, particularly preferred are compounds of formula (I) in which:

KI - hydrogen atom, methyl or methoxyl group,

KO - hydrogen atom or methyl group,

K2 - hydrogen atom,

X is a nitrogen atom, n is 1 or 2, t is 1 or 2,

KZ is a hydrogen atom, and then the compounds of formula (I) comprise a quaternary ammonium, or, alternatively, KZ 7/o Absent, and then the compounds of formula (I) comprise a secondary or tertiary amine,

KA - hydrogen atom,

C1-C4-alkyl group,

a C6-C7 cycloalkyl group, a pyridyl, pyrimidyl or pyrazinyl group optionally substituted with a C1-C4 alkyl group, a heteroarylcarbonyl group, wherein the heteroaryl group is a furyl or pyridyl group, a phenylcarbonyl group, wherein the phenyl group is optionally substituted with a halogen atom , (C3-C5)-alkylcarbonyl group, group -CHO)PSOOK, in which p is 0 or 1, and K is a C1-C4-alkyl group, phenylsulfonyl group, phenyl group substituted by 1-3 groups, independently selected from one, among a metal group, a nitro group, an amino group, a hydroxyl group, a halogen atom, a trifluoromethyl group, a methoxy group, a (C1-C4)-alkoxyphenyl group, a dimethylamino group, a -MHCNO group or a -MHCOV group", in which VK -

C1-C4-Alkoxyl or C1-C4-Alkyl group, and this C1-C4-Alkyl group is optionally substituted with a dimethylamino group, c -(CH»)p-phenyl group, where p is 1, 2, C or 4 , o -(CH»)p-pyridyl group, in which p is from 1 to 3, -(CH»)p-thienyl group, in which p is 2, cC6-C7-heterocycloalkyl group, optionally substituted by a metal group or the group -SOOK, in which K -

C1-C4-alkyl group, or, in another variant, the most preferred are those compounds of formula (I) in which:

K1 - hydrogen atom,

K2 and Kg are, independently of each other, a hydrogen atom or a metal group, -

X is a carbon atom, c n equals 1 or 2, t equals 1, c

KZ - hydrogen atom, group -MK5Kb, group -M(CH3)zk, group -MNSOK?7, group -SOMNK5, group -MNSOMN»5, - group -OH or group -SHOOH,

K4 is a hydrogen atom, a benzyp group, a phenyl group, as an option, is substituted by 1-3 groups chosen independently of each other from a halogen atom and a trifluoromethyl group, - a heteroaryl group, namely, an imidazolyl group, as an option, is substituted by a methyl or by a pyridyl group, ts group -MK7K8, and"? provided that when KA is a group -"MK7KV8, KZ is not one of the groups -MAK5Kb, -MNSOK?7, -MNSOMN"" and -OH,

K5 and Kb are, independently of each other, a hydrogen atom or a C1-C4 alkyl group,

K7 and k8 are, independently of each other, a C1-C4-alkyl group or together they form a saturated -I 5-7- ring, which, as an option, includes an additional nitrogen atom, and this ring is on a nitrogen atom, including the atom nitrogen, to which K7 and K8 groups are attached for the formation of quaternary ammonium, as an option, di can be replaced by a methyl group or a -SOOK" group, in which K" is a (C1-C4)alkylphenyl group, (ee) with the exception of two compounds , in which КИ, К2, К2, КЗ are Н, Х - C, п-т-1, and К4 - 4-imidazolyl or ts o-methyl-4-imidazolyl group.

Hereinafter, the term "leaving group" means a group that can be easily cleaved from a molecule by heterolytic cleavage of a bond with the loss of an electron pair. Such a group can easily be replaced by another through a substitution reaction. Such depleting groups are, for example, halogens or an activated hydroxyl group such as mesyl, tosyl, triflate, acetyl, etc. Examples of splitting groups and a description of their preparation can be found in "Aamapsez ip Ogdapis Spetivigu", ).Magsp Zga Edibyop, UMiu Ipiegzsiepse, 310-316.

For the preparation of compounds of formula (I) according to the invention, the synthesis procedure according to

F, Scheme 1. According to this procedure, derivatives of formula (II) in which K1, K2, K2 and n are identical to those defined above, where A is a leaving group, preferably a halogen, are reacted in the presence of an amine of formula (I ), where X,

KZ, K4 and t are identical to those defined above, in a solvent, which can be an alcohol, for example, isoamyl, an ether, for example, THF or THME (triethylene glycol monomethyl ether) or a hydrocarbon, for example, toluene, at a temperature between room temperature and the boiling point of the solvent, for obtaining the compound of formula (I). The reaction can be carried out in the presence of a base, for example, 2,6-dimethyllutidine or sodium tert-butoxide, in the presence of alkali metal halides, for example, potassium fluoride, or in the presence of palladium or nickel catalysts, as described (for example, in EP application 646 583 or in U. Mea. Spet. (1986), 29, 1178-1183, 65 Temapedhop IeKeg (1997), 32, 5607-5610, Tei(gapedhop I etseg5 (1999), 55, 12829-12842 and Teianpeagtop Ieegz (1999), 40, 6875-6879).

When a compound of formula (I) includes a free primary or secondary amine function, it can also be prepared by reacting a derivative of formula (I) with an amine of formula (II) where said amine function is protected by a conventional amino protecting group, e.g., tert-butylcarbamate (800). The compound of formula (I) obtained in this way,

THAT contains a protected amine function, is processed according to one of the known methods and the desired compound (I) is obtained, which contains a free amine function. Examples of amino protecting groups and deprotection methods can be found, in particular, in the work of T.MU. (heepe, R.O.M. MUtsiv, "Rgoyesiime Sgotsrz ip Ogdapis Zupipeziz (protecting groups in organic synthesis)", U. UMPuU, Ed., 1991.

Scheme 1; t-va t all would -- vel sn), and o sn, o vd -on o) (in GI

Compounds of formula (II) can be prepared according to Scheme 2 under operating conditions known to those skilled in the art, in particular by reacting a compound of formula (II) in which C1, C2, n and C2 are identical to those defined above with a halogenating agent, for example, phosphoryl chloride

Scheme 2 chn, in "the bottom of the puh 3 nn -sh In vk spnsenyutute Mi s, o su, s sn),

Oda va sv" coffee m "my" (about approx

MI o cho --t- -E Y Ukh t, ok oyi «rya so mu obov , «- m

Compounds of the formula (IM) can be prepared according to the procedure of Scheme 2. According to one of the variants of the procedure, a diamine of the formula (M), in which KI, К2, КЕ" are identical to those defined above, is reacted with a phosgene derivative, for example, carbonyl dimadazole ( 50). MII), in which n-1 and K2' are H, or by an agent of the formula (IX, K - C1-C4-alkyl), where Y is a leaving group, in which K2 and K2 are identical to those defined above, with the production of products of the formula (MII ), in which p-2. Compounds (MI) obtained in this way are converted into carboxylic acids (MI, K - H) or into "acid derivatives, for example, acid chlorides (MI, K - C1) with subsequent cyclization in under the conditions known to specialists, and by directly obtaining intermediates of formula (1). This solution is similar to the one described in the application UR Z p 55111406 or in Teiganedgop I eTsegz (1995), 36,1387 -1390. "» In another variant, compounds of the formula (I), where K2 and K2 are not a hydrogen atom, can be prepared from "the corresponding compounds (II), in which K2" is a hydrogen atom, by alkylation with a reagent of the type K2"7, where 2 is a cleavage group, preferably iodine. This reaction can be carried out in a solvent such as DMF, ether or THF in the presence of a base by methods known to those skilled in the art. ш- Compounds of formulas (II), (M), (MI), (MY) and (X) can be purchased commercially or prepared in a way

GI is known to specialists.

The object of the invention is also new synthetic intermediates of the formula (II). because the following examples illustrate the invention. The numbers of the compounds given as examples correspond to the numbers in the table below, which gives the chemical structures of the compounds according to their numbers.

Example 1. Preparation of intermediates of formula (I) c» 1.1. Preparation of 2-chloro-4,5-dihydro-imidazoi|4,5,1-i)quinolin-b-one (А - СТ, К1- НН, К2и К2 is H, n-1)

This compound is obtained from the compound 4H-imidazo|4,5,1-iii| quinoline-2,6-"1H,5H)dione (IM), described in the patent

of Japan OR 55111406. 10 g of the compound (IM) is refluxed with 38 bml of phosphorus 22 oxychloride and b, 3g of ammonium chloride for 1.5 hours. in a 250 ml three-necked flask with a reflux condenser.

HF) The reaction mixture is cooled, poured into ice, and a 2095 aqueous ammonium solution is added with vigorous stirring until pH is reached. The mixture is extracted (2 x 250 ml) with ethyl acetate, dried over magnesium sulfate, filtered and evaporated. The obtained 9.81 g of solid substance is used without further purification in the next operation. "H NMR (200 MHz, 5 1/million) DMSO 06: 7.8 (4, 1H), 7.5 (4, 1H), 7.3 (i, 1H), 4.5 (i, 2H), 3.0 (i, 2H). bo 1.2 Preparation of 1-chloro-8,9-dihydro-7H-2,9a-diazabenzo|sa|azulene-b-one (A - ST, K1- H,K2 and K2 are H , n-2) 1.2.1. Sodium hydride ethyl-3-(2-chlorobenzimidazol-1-yl)butyrate in the form of 6bO905 dispersion in oil (2.88 g, 72 mmol) is introduced in a nitrogen atmosphere into a 1-liter three-necked flask with with a magnetic stirrer, an additional tube, and a condenser. The sodium hydride is washed twice with pentane, a small amount of DMF is added, and then a solution of ethyl 4-bromobutyrate (14.78 g, 72 mmol) in anhydrous DMF (200 mL). After stirring for 1 hour at 65°C at room temperature to 2-chloro-1H-benzimidazole (10.0g, 65.5mmol) dissolved in anhydrous DMF (200ml) is added to the mixture. The reaction mixture is heated at 6592C for 8 hours and kept overnight at room temperature. After evaporation of DMF, the residue is taken up in ethyl acetate and the organic phase is washed with saturated sodium chloride, dried over magnesium sulfate, filtered, etc center Flash chromatography of the crude product (22g) on silica gel (750g) eluting with a gradient of 1095-3090m ethyl acetate in petroleum ether afforded the desired compound as a yellow oil (16.58g, 9596). "H NMR (ZOOMHC, 5 1/million) SOSIa: 1.25 (I, ZN), 2.15 (dsipE., 2H), 2.40 (i, 2H), 4.15 (dsagiei, 2H), 4.25, (6 2H), 7.20-7.40 (t, 2H), 7.70 (aa, 1Hn). 1.2.2 Lithium 3-(2-chloro-1-benzimidazolyl)butoxide

Ethyl ester (16.58g, 62.2mmol) dissolved in THF (180ml) is placed in a 1-liter 70 round-bottom flask with magnetic stirring and an aqueous solution of lithium hydroxide (1.49g, 24mmol, 100ml distilled water) is added. . The mixture is left overnight at room temperature, THF and water are evaporated, and the residue is added to ethyl ether (2 L) and stirred for 2 hours. The obtained white precipitate is filtered, washed with ethyl ether and dried under a fan vacuum pump over phosphorus pentoxide, obtaining the desired compound in the form of white crystals (14g, 92965). This compound is used without purification in the next operation. "H 72 NMR (ZOOMHCC, 56 tl/ml DMSO O6-EO20: 1.85 (t, 2H), 1.95 (t, 2H), 4.20 (Hii, 2H), 7.25 (t, 2H ), 7.55 (a, 1H), 7.60 (a, 1). G0-M5: МН. - 239 (acid). 1.2.3.1 -chloro-8,9-dihydro-7H-2,9a- diazabenzoi|sa|-azulen-6b-one

The lithium salt (11.95 g, 49.7 mmol) is placed in a 2-liter three-necked flask with a magnetic stirrer, a condenser, and an additional tube for introduction under an argon atmosphere, and 1,2-dichloroethane distilled over phosphorus pentoxide (1 l) is added. Add oxalyl chloride (8.55 ml, 102 mmol) with stirring and heat the reaction mixture for 15 minutes. at approximately 402. Aluminum chloride (19.54 g, 154.5 mmol) is added to the obtained intermediate acid chloride and the mixture is kept under reflux according to The mixture is cooled, poured into an ice-salt mixture and extracted with 1,2-dichloroethane, the organic phase is washed with saturated sodium chloride solution, dried over magnesium sulfate and filtered. The solvent was evaporated (and the crude product (10.6g) was flash chromatographed on silica gel, eluting with 2095% ethyl acetate in DCM to give the desired product as white crystals (7.06g, 6595). "H NMR (300 MHz, 5 t1/million) SOSI5: 2.40 (dzipi, 2H), 3.15 (, 2H), 4.40, (i, 2H), 7.35 (Ii, 1H), 7 .95 (a, 1H), 8.05 (a, 1nH). And C-mM5: MH. -221. 1.3. Preparation of 2-chloro-5-methyl-4,5-dihydroimidazo|4,5,1- 1) quinoline-b-one (A - ST, K1-H, K2- SNU, K2 - H, so pet) 3o 1.3.1. Methyl-1-methyl-3-(2-chloro-1-benzimidazolyl)propionate -- 2-chloro-1H-benzimidazole (15.25g, 1b0mmol) is dissolved in chloroform (100ml) and placed in a nitrogen atmosphere in a 1-liter three-necked flask with a magnetic stirrer, an additional tube and a condenser. Add Tgyop B so (47ml, 110mmol ) and methyl methacrylate (107 ml, 1 mol). The reaction mixture is maintained under a reflux condenser M for 2 hours and after cooling, the chloroform is evaporated. The residue is added to ethyl acetate and the organic phase is washed three times with water and once with saturated sodium chloride solution. Crude product (10.6 g) - flash chromatography on silica gel (ikg) with gradient elution with 3095-7090 m ethyl acetate in petroleum ether and obtain the desired product in the form of white crystals iv (10.1g, 4095). "H NMR (Z00OMHC, 5 1/mln) DMSO Ob: 1.15, (y, ЗН), 3.05 (t, 1Н), 3.50 (v, ЗН), 4.25 (ad, 1Н) , 4.50 (da, 1), 7.25 (t, 2H), 7.60 (t, 2H). " Lithium 1.3.2.1-methyl-3-(2-chloro-1-benzimidazolyl)-propionate 2 c This compound is obtained as in preparation 1.2, treating also methyl-1-methyl-3-(2-chloro-1-benzimidazolyl)propionate with lithium hydroxide. EYUO20: 1.35 (0, ZN), 2.60 (t, tn), 4.10 (aa, 1n), 4.40 (aa, 1n), 7.25 (t, 2H), 7.55 (a, 1), 7.60 (a, 1H).

Is6-mM5: MN. -239 (acid). 1.3.3. 2-chloro-5-methyl-4,5-dihydroimidazo|4,5,1-1i||Y-quinolin-b-one -I This compound is obtained as the compound in preparation 1.2 by treating it with oxalyl chloride to obtain from the acidic intermediate chloride and then aluminum chloride. "H NMR (300 MHz, 5 1/million) of DMSO O6: 1.40 (4, ZN), 3.20 (t, 1H), 4.10 (ad, 1H), 4.65 (ad, 1H), 7.45 (her, 1n), 7.70 (a, 1H), 7.85 (a, 1). HO-M5: МН я -221. (ee) 1.4. Preparation of 2-chloro-4,5- dihydro-9-methylimidazoi|4,5,1-Y||Yquinolin-b-one (А - C1,. K1 - 9-CH3, Kk ik is H, -l 20 pl) 1.4.1.2-hydroxy-4- methylbenzimidazole

I) 2,3-diaminotoluene (5g, 41mmol), 1,1-carbonyldiimidazole (7.3g, 45mmol) and 100ml of anhydrous DMF are added in an argon atmosphere to a 250-milliliter two-necked flask with magnetic stirring. The mixture is heated at 90-95 for 4 hours, the solvent is distilled under vacuum, the residue is added to water (25O0ml) and extracted with ethyl acetate 59 (3x2B5Oml). The insoluble product formed during the extraction is separated (4.8 g) and the combined organic phase is washed with a saturated solution of Masi, dried over Na 2 O, filtered and concentrated to give 1.2 g of the desired product (bg, quantitative). H NMR (SO0MHC, 5 1/ml) DMSO Ab: 2.27 (z, 3H), 6.72 (t, 2H), 6.82 (t, 1H). 1.4.2. 2-chloro-4- methylbenzimidazole in 2-hydroxy-4-methylbenzimidazole (5.92g, 40mmol) and 40O0ml of phosphoryl chloride are introduced into a 250-ml two-necked flask under argon atmosphere, with magnetic stirring. The mixture is refluxed for 20 hours and the phosphoryl chloride is evaporated under vacuum. The solid substance is introduced in water (250ml), neutralize to pH-8 with 28956m aqueous ammonium, and the aqueous phase is extracted with ethyl acetate (3x250ml). After the usual work-up, the desired product (9395, 6.23g) is obtained. DMSO 06: 2.47 (b, 3H), bb TO1 (a, 1H), 7.11 (b tn), 7.32 (a, 1Hn). 1.4.3. Methyl-1-methyl-3-( 2-chloro-4-methyl-1-benzimidazolyl)propionate

This compound is obtained as in Example 1.3.1 (7.85 g, 9495). "H NMR (SO0MHC, 5 1/million) DMSO Ab: 2.48 (in, ЗН), 2.86 (I, 2Н), 3.56 (in, ЗН), 4.49 (И, 2Н), 7.06 (49, 1H), 7.19 (i, 1n), 7.44 (an). Lithium 1.4.4.1-methyl-3-(2-chloro-4-methyl-1-benzimidazolyl)propionate

This compound is prepared as in Example 1.3.2 (6.94 g, 9496). "H NMR (SO0MHC, 5 1/ml) DMSO O6: 2.3 (da, 2H), 2.48 (5, ЗН), 4.32 (ad, 2H), 7.01 (a, 1H), 7.15 (Yii, 1H), 7.41 (a, 1H) (acid). 1.4.5. 2-chloro-4,5-dihydro-9-methylimidazo|4,5,1-i|)quinoline- 6-on

This compound is prepared as in Example 1.3.3. (4.72g, 7695). "H NMR (SO0MHC, 5 1/million) DMSO Ab: 2.58 (z, ЗН), 3.05 (i, 2Н), 4.53 (I, 2Н), 7.19, (а, 1Н) , 7.52 (a, 1Hn). 70 Example 2. 1-(6-oxo-5,6-dihydro-4H-imidazo|4,5,1-yl)quinolin-2-yl)-4-piperidino- piperidine (KI, K2, K2,

KZ is H, Ka - 1-piperidyl, X - C, n-t-1) (compound 45) 400mg of chlorine derivative formula (II) (item 1.1), bml of DMF, 7mg of potassium fluoride, 0.2ml of 2.6 -lutidine and 500 mg of 4-piperidinopiperidine are introduced into the reaction together for 2 hours. at 140 C. After evaporation of the solvent, the residue is chromatographed on silica gel (eluent: ДЧМ 895 methanol). 375 mg of the product is obtained in the form of a whitish solid. IN NMR (200 MHz, 5 1/million) DMSO 06: 1.2-2.2 (t, 12Н) 3.0 (t, ЗН), 3.2-3.4 (t, 4Н), 4.2 (9, 2H), 4.65, 2H), 7.4 (, 1H), 7.6, (a, 1n), 7.8 (a, 1Hn).

Example 3.

Chloridi-Methyl-1-(1-(6b-oxo-5,6-dihydro-4H-imidazoi|4,5,1-yl)quinolin-2-yl)-4-piperidinyl|piperidine (K1, 2,

K2, KZ is H, KA - M-methyl-1-piperidyl, X - C, n-1, t-1) (compound 48) 3.1.4-("M-piperidino)-Bos-piperidine 3.98g 4 -oxo-M-Voc piperidine, 1.7 g of piperidine and 7.1 g of Ti (IM) isopropoxide are mixed in a three-necked round-bottomed flask under nitrogen, and the mixture is left to stir for 1 h. at room temperature.

Add 20 ml of absolute ethanol and 850 mg of MavNzsM. The mixture is left to react for 17 hours. at room temperature, add bml of water and stir the mixture for 5 minutes. and filtered through Whatman paper.

The pink solution is evaporated, the residue is added to 100 ml of ethyl acetate, the solution is dried over magnesium sulfate and (o) evaporated. The residue is chromatographed on 100 g of silica and eluted with acetone, obtaining 2.2 g of oil, which crystallizes. The NMR spectrum corresponds to the expected structure, and the product is used without further purification in the next operation. so 3.2. M-Boc-4-(M-methylpiperidinium) piperidine chloride

The compound of item 2.2 is mixed with 5 ml of CH with 17h. in the dark and evaporate. The obtained white crystals (3.10 Hg) are used without further purification in the next operation. so 3.3. 4-(M-methylpiperidinium) piperidine chloride

The crystals obtained above are suspended in 20 ml of DCM and bml of a saturated solution of hydrochloride in CM ether is added

The gummy precipitate is dissolved in 20 ml of methanol, evaporated to dryness and added to 5 ml of methanol. This solution is cooled to 092C, 1.35 ml of sodium methoxide (3095 in methanol) is added and the mixture is stirred for 15 minutes, filtered and evaporated with a vacuum pump. The obtained amine is used without further purification in the next operation. 3.4. 1-Methyl-1-(1-(b-oxo-5,6-dihydro-4H-imidazo|4,5,1-i)quinolin-2-yl)-4-piperidyl|piperidine chloride. « 400mg of 2-chloro-4,5-dihydro-6bH-imidazo|4,5,1-irnoline-b6-onuubml of DMF, 7Omg of potassium fluoride, 0.2ml of 2,6-lutidine 2s and 1,6bg of 4-( M-methylpiperidinium)upiperidine chloride is introduced into a three-necked flask under argon and left to stir for 5 hours. at 1402C. The mixture is evaporated with a vacuum pump and the residue is chromatographed with 70 mg of sodium chloride (MegskK) (eluent: DCM with 1095 methanol and 0.596 triethylamine), obtaining 50 mg of pure product. The NMR spectrum corresponds to the desired structure.

Example 4. 2-(4-(4-dimethylaminophenyl)piperidin-1-yl)4,5-dihydroimidazo|4,5,1-quinolin-b-one (К1, К2, Кк -i is H, КЗ is - , K4 - paradimethylaminophenyl, X - M, p-t-1) (compound 58) 4.1.1-(tert-butoxycarbonyl)-4--4-dimethylaminophenyl)piperazine and 1-bromo-4-M,M-dimethylaniline (0.85g, 4.25mmol), palladium acetate (0.039g, 0.17mmol),

Go) 2,2'-bis(diphenylphosphine)-1,1"-binaphthyl (VIMAR) (0.17g, 0.25mmol) and IIVyOK (0.67g, 5.p95mmol) are placed in a 5o flask with a rounded bottom, equipped condenser, under a nitrogen atmosphere, with magnetic stirring. The flask - purge 3 times with nitrogen, add toluene (2b5ml) and M-tert-butoxycarbonylpiperazine (0.95g, 5.mmol) and

GC) the reaction mixture is kept under reflux for 20 hours. After cooling to room temperature, ethyl acetate is added and the organic phase is washed twice with water. After drying the organic phase over sodium sulfate, filtering and concentrating the residue (1.38 g) is chromatographed on silica gel with gradient elution with DCM/ethyl acetate (from 9:1 to 1:1 ), yielding the desired compound (5095, 0.67g). "H NMR (30OMHC, 5 1/million) SOSI": 1.47 (in, 9H), 2.99 (t, 4H), 3.57 (t , 4H), 6.72 (a, 2H), 6.89 (49, 2H). at 4.2. M-1--4-dimethylaminophenyl)piperazine ime) The product of Example 1.1 (0.67 g, 2.2 mmol) is dissolved in trifluoroacetic acid (2 Oml) and subjected to magnetic stirring for 2.5 hours. at room temperature. After evaporation of 60% trifluoroacetic acid, the residue is added to a saturated solution of sodium carbonate and the aqueous phase is extracted twice with ethyl acetate. The combined organic phases are washed to neutrality with saturated sodium chloride solution, dried over sodium sulfate and concentrated. Chromatography of the residue on silica gel (DHM/methanol/MH.OnH (95:5:0.1)) gave the desired product (6990, 0.31g, CT: 0.1). 4.3... 2-(4--4-dimethylaminophenyl)piperazin-1-yl|-4,5-dihydroimidazoi|4,5,1-yl)quinolin-b-one 6E Chlorine intermediate (item 1,1) (0.2g, 0.969mmol), one ml of triethylene glycol monomethyl ether (TGME), lutidine (0.125ml, 1.07mmol), cesium fluoride (0.148g, 0.969mmol) and a solution of the derivative of Example 1.2 (0.219g, 1.07mmol) in

TGME (Tml) is introduced into a round-bottomed flask with a condenser, with magnetic stirring. The reaction mixture is heated at 1402C for 1.5 hours. and after cooling add water. The mixture is extracted twice with ethyl acetate, the organic phases are washed twice with water, dried over sodium sulfate, filtered and concentrated. The residue (0.38g) is chromatographed on silica gel (with ethyl acetate), the resulting oil (0.246g) is introduced into a small amount

DCM and crystallize by adding ether. A solid corresponding to the desired compound (0.208g, 5795) was filtered.

Is-mM5: MH -376. "H NMR (Z6OMHC, 5 1/ml) DMSO Ab: 2.79 (z, 6H), 3.0 (i, 2H), 3.14 (t, AN), 3.55 (t, 4H), 4.47 (1, 2H), 6.71 (a, 2H), 6.91 (a, 2H), 7.15 (aa, 1n), 7.35 (a, 1n), 7.6F (a , 1Hn).

Example 5. 70. 2-ID-(4-tert-butoxycarbonylaminophenyl)piperazin-1-yl|-4,5-dihydro-imidazo|4,5,1-i)quinoline-b-c0n. (KK, 0 K2, Ky is H, KZ is -, X - M, K4 - 4-tert-butyloxycarbonyl-aminophenyl, p-t-1) (compound 57) 5.1. 1--2-(trimethylsilyl)ethylcarbonyl|/|-4-(4-nitrophenyl)piperazine

A solution of 1-(4-nitrophenyl)piperazine (10g, 48.3mmol) and 2-(trimethylsilyl)ethyl-p-nitrophenylcarbonate (14.4g, 50.7mmol) in THF (220ml) is refluxed according to with magnetic stirring and 75 then stir for 20 hours. at room temperature. The reaction mixture is concentrated, the residue is added to DCM and the organic phase is washed 4 times with 1 M sodium hydrochloride and twice with water. The organic phase is dried over sodium sulfate, filtered and concentrated; the oily residue is used without further purification in the next operation (12g, 7195). "H NMR (300 MHz, 5 1/million) SOSIv: 0.04 (v, 9H), 1.02 (t, 2H), 3.43 (t, 4H), 3.65 (t, 4H), 4 .22 (t, 2H), 6.82 (a, 2H), 8.13 (a, 2H). 5.2. 1--2-(trimethylsilyl)ethylcarbonyl/|-4-(4-aminophenyl)piperazine

A mixture of the nitro derivative obtained above (12 g, 34.2 mmol) and 4-5 Raney nickel blades in ZOO ml of ethanol is kept in a hydrogen atmosphere, at atmospheric pressure, for 18 hours, with vigorous magnetic stirring. After filtering and concentrating, the residue is used without further purification in the next operation; the product obtained (yield 5095 according to NMR and I C-M5) is difficult to purify. "H NMR (300 MHz, 5 s 1/million) SOSIz: 0.04 (v, 9H), 1.03 (t, 2H), 2.96 (t, 4H), 3.59 (t, 4H), 4.18 (t, 2H), aromatic protons not He) can be assigned due to the presence of impurities. 5.3... 1--2-(trimethylsilyl)ethylcarbonyl/)-4-(4-tert-butoxycarbonylaminophenyl)-piperazine

The crude reaction mixture from the previous operation (estimate - Zimmol) and di-tert-butyl dicarbonate (7.5 g, 34.1 mmol) in THF (5 Oml) are placed in a round-bottomed flask with a condenser and kept under reflux for 44 hours. THF is evaporated, the residue is added to a mixture of water/ethyl acetate and the organic phase is washed twice with water. The organic phase is dried over sodium sulfate and concentrated, the residue is chromatographed on silica gel (with dichloromethane/ethyl acetate (1:1). The impure product is used without further purification in with the next operation. | С-М5: МН. -422. Ge

The newly obtained intermediate (Zg, ca. 7.12 mmol) and tetrabutylammonium fluoride (3.37 g, 10.68 mmol) in tgF (bOml) are placed in a round-bottomed flask equipped with a condenser under magnetic stirring. t

The reaction mixture is refluxed for 2 hours, concentrated, and the residue is added to water with ethyl acetate. The organic phase is washed twice with water and saturated sodium chloride solution, dried over sodium sulfate and concentrated. The desired compound (0.99 g, 50906 in 3 operations) was obtained by chromatography on "20 silica gel with the eluent DCM/methanol/mNAOH (90:10:0.1). "H NMR (Z0OMHC, 5 1/million) SOSIv: 1.50 (z, 9H), 3.04 z (t, 8H), 6.60 (v, 1H), 6.87 (9, 2H), 7.23 (a, 2H). c 5.5... 2-I4-(4-tert-butoxycarbonylaminophenyl)piperazin-1-ylI|-4,5-dihydroimidazoi|4,5,1-iDhinolin-b-one: z» Chlorine intermediate item 1.1 (0.7g, 3.39μmol), TGME (7ml), lutidine (0.43ml, 3.7μmol), cesium fluoride (0.514g, 3.39mmol) and 1-(4-tert) -butoxycarbonylaminophenyl)-piperazine (1.03 g, 3.7 mmol) is placed in a round-bottomed flask equipped with a condenser, with magnetic stirring. The reaction mixture is heated at 1402С-I for 2 hours, after cooling, water is added and extracted twice with ethyl acetate. Organic phases washed twice with water, dried over sodium sulfate, filtered and concentrated Chromatography of the residue on silica gel (eluent DCM/ethyl acetate with a gradient from 75:25 to 1:11) gave the desired compound, which was crystallized in DCM/ether to give a solid (1.1 g, 7396). I C-M5: MH "448. "H NMR (500 MHz, 5 1/ml) DMSO 06: 1.45 shun 20 (5, 9H), 3.00 (5 2H), 3.22 (t, 4H), 3.55 (t, 4H), 4.47 (5 2H), 6.91 (a, 2H), 7.15 (aa, 1), 7.33 (t, 2H), 7.35 (a, 1H), 7.61 (a, 1n). c» Example b. 2-(4-(4-aminophenyl)piperazin-1-yl)|-4,5-dihydroimidazo-|4,5,1-i)quinolin-b6-one dihydrochloride (K1, K2, KO is H, KZ is -, K4 - para-aminophenyl, X - M, p-t-1) (compound 50)

A solution of gaseous hydrochloride in ethanol is added to the compound of Example 5 (0.22 g, 0.497 mmol) and the reaction mixture is stirred at room temperature for 2 hours. The mixture is concentrated and after trituration with ether, the desired compound is obtained as a solid (0.155 g, 8096). "H NMR (500 MHz, 5 1/ml) DMSO 06: 3.06 (i, 2H), 3.63 (t, 4H), 3.84 (t, 4H), 4.65 (5 2H), 7 ,10 (a, 2H), 7.26 (a, 2H), 7.36 (aa, 1), 7.54 (a, 1), 7.71 (a, tn), ime) 10.06 ( broad peak, 2H).

Example 7. 2-(4-(4-acetamidophenyl)piperazin-1-yl|-4,5-dihydroimidazo|4,5,1-i)quinolin-b-one (КИ, К2, КУ is 60 N, КЗ is -, K4 - para-acetamidophenyl, X - M, p-t-1) (compound 60)

The compound of Example 6 (0.20g, 0.48mmol) and triethylamine (8µl, 0.572mmol) were added to a solution of acetic acid (27µl, 0.468mmol) and carbonyldiimidazole (0.152g, 0.93bmmol) in DMF (4ml). The reaction mixture is subjected to magnetic stirring at 702C for 20 hours. After evaporation of DMF under vacuum, the residue is added to water, ground and the solid substance is filtered. Washing the solid with a minimal amount of 62 DCM and ether gave the desired compound (0.12g, 6496). "H NMR (500 MHz, 5 1/million) DMSO Ob: 1.99 (in, ZN), 3.00 (i, 2H),

3.25 (t, 4H), 3.55 (t, 4H), 4.48 (Ii, 2H), 6.94 (a, 2H), 7.15 (ad, 1n), 7.35 (a , 1), 7.44 (a, 2H), 7.61 (d, 1H), 9.70 (c, 1H).

Example 8. Dihydrochloride of 2-(4-p-propylpiperazin-1-yl)-4,5-dihydroimidazo|4,5,1-i||-quinolin-b-one (KI, K2,

K2, KA is H, X - M, KZ - p-propyl, p-t-1) (compound 26)

Intermediate of formula (II) (item 1.1) (0.2g, 0.969mmol), 1ml tri-ethylene glycol monomethyl ether (TGME), lutidine (0.37ml, 3.0mmol), cesium fluoride (0.148g, 0.969mmol) and a solution M-propylpiperazine dihydrobromide (0.296g, 1.18mmol) in THME (ml) is placed in a round-bottomed flask equipped with a condenser under magnetic stirring. The reaction mixture is heated at 1409 for 2 hours. 1-5 minutes, after cooling, add a saturated solution of sodium carbonate and sodium chloride, and the mixture is extracted twice with ethyl acetate. Organic phases 7/0 are washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on silica gel with the eluent DXM/methanol/m.onN (95:5:0.5) and the obtained dihydrochloride salt of butter (0.203 g) is synthesized by dissolving in a small amount of DXM and adding a saturated solution of gaseous hydrochloride in anhydrous ether. The solid corresponding to the desired product (0.23 g) was filtered off. IS-M5: MN -299. "H NMR (Z6OMHC, 5 1/mL) DMSO Ob: 0.94 (i, ЗН), 1.78 (t, 2Н), 75 3.08 (t, 4Н), 328 (t, 2Н), 3 .62 (32H), 3.88 (t, 2H), 4.25 (t, 2H), 4.65 (5 2H), 7.42 (B 1H), 7.60 (a, 1H), 7 .76 (9.1 N), 11.66 (5.1 N).

Example 9. 2-(4-tert-butyloxycarbonylpiperazin-1-yl)-4,5-dihydroimidazo|4,5,1-y|-quinolin-b-one (KI, KO,

KO is H, KZ is -, X is M, KA is tert-butyloxycarbonyl, p-t-1) (compound 12)

Intermediate item 1.1 (0.25g, 1.2mmol), THME (1.5ml), lutidine (0.155ml, 1.33mmol), cesium fluoride (0.184g, 1.21mmol) and tert-butyl-1-piperazinecarboxylate solution (0.237g, 1.28mmol) in THME (1.5ml) is placed in a round-bottomed flask equipped with a condenser under magnetic stirring. The reaction mixture is heated at 1202C for 1 hour, after cooling water is added and this mixture is extracted twice with ethyl acetate. The organic phases are washed twice with water, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on silica gel with the eluent DCM/ethyl acetate (1:1) and the desired compound is obtained in the form of a solid substance (0.315 g, "M 7396). IO-M8: MH -357. "H NMR (500 MHz, 5 1/ml) DMSO Ab: 1.51 (in, 9H), 3.07 (Hi, 2H), 3.46 (t, 4H), 3.58 g) (t, 4H ), 4.52 (i, 2H), 7.23 (i, 1H), 7.43 (d, 1Hn), 7.68 (a, 1H).

Example 10. Dihydrochloride 2-(piperazin-1-yl)-4,5-dihydroimidazoi|4,5,1-i)quinolin-b-one (КИ, К2, К2, КЗ,

KA is H, X - M, p-t-1) (compound 13)

A saturated solution of gaseous hydrochloride in anhydrous ether is added to the compound of Example 9 (0.1 g, i. 028 mmol), previously dissolved in a minimum amount of methanol, and the mixture is subjected to magnetic stirring at room temperature overnight. The mixture was concentrated and the residue was crystallized from methanol/DCM to give the desired compound as a solid (0.077). JIS-M8: Mnya -257.H NMR co (50 OMHC, b5 T/million) DMSO 06: 3.12 (6 2H), 3.95 (t, 4H), 3.94 (t, 4H), 466 ( 5 2H), 7.43 (B 1n), 7.61 (a, cm 1H), 7.89 (a, 1Hn), 9.63 (85.2H).

Example 11. Dihydrochloride of 2-(4-acetylpiperazin-1-yl)-4,5-dihydroimidazoi|4,5,1-i)quinolin-b-one (KI, K2, -

KO is H, KZ is -, K4 - SOSNU", X - M, p-t-1) (compound 15)

The compound of Example 10 (0.085g, 0.26mmol) and triethylamine (/bml, 0.52mmol) are added to a solution of acetic acid (2O0ml, 0.349mmol), hydroxybenzotriazole (0.055g, 0.349mmol) and diisopropyl azodicarboxylate (BbBmcl, 0.349 mmol) in DCM (Bbml). The reaction mixture is magnetically stirred at room temperature overnight and diluted with ethyl acetate and 1M hydrochloric acid solution. The crude product is obtained by the usual acid-base extraction and washing with water followed by drying the organic phases over sodium sulfate and evaporation. Chromatography on silica gel eluting with DCM/ethanol (95:5) gave the desired compound (0.04g). And S-M8: MN. -299, "H NMR (500MHz, 5 1/ml) DMSO Ob: 2.13 (in, ЗН), 3.08 (Іі, 2Н), 3.46 (t, 2Н), 3.52 (t, 2H), 3.70 (t, 4H), 4.54 (I, 2H), 7.23 (i, 1H), 7.43 (a, 1Hn), 7.68 (a, 1H). -I Example 12. Dihydrochloride /2-I4-(4-pyridyl)piperazin-1-yl)-4,5-dihydroimidazo|4,5,1-i)quinolin-b-one (KI,

K2, Kg is H, KZ is -, KA - 4-pyridyl, X - M, p-t-1) (compound 23) co Intermediate p.1.1 (0.2g, 0.969mmol), THME (ml), lutidine (125 μL, 0.969 mmol), cesium fluoride (0.148 Hg, CO 0.969 mmol) and a solution of 1-(4-pyridyl)piperazine (0.238 g, 1.02 mmol) in THME (mL) are placed in a round-bottomed flask

BOTTOM, equipped with a condenser, with magnetic stirring. The reaction mixture is heated at 1402C for an hour. - BOkhvil., after cooling add a solution of sodium carbonate and solid sodium chloride and extract the mixture

GC) twice with ethyl acetate. The organic phases are washed twice with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on silica gel with eluent

DCM/methanol/mn OH (95:5:0.5) to give the desired compound as a solid (0.071g). I С-М8: МН вв 334. H NMR (Z36OMHC, 5 µl/mL) DMSO 06: 3.01 (µ 2Н), 3.58 (t, 8Н), 4.51 (, 2Н), 6.91 (9, 2), 7.18 (i, 2H), 7.37 (a, 1), 7.63 (9, 1H), 8.20 (4 2H). i) Example 13. Dihydrochloride /2-(4-benzylpiperidin-1-yl)-4,5-dihydroimidazo|4,5,iR)-inolin-b-one (KI, KO, ko K2", KZ is H, KA - benzyl, X - C, p-t-1) (compound 1)

Intermediate No. 1.1 (0.206g, tTmmol), dissolved in anhydrous toluene (ml), potassium tert-butoxide (0.157mg, 60 14mmol), 2,2-bis(diphenylphosphine)-1,1-binaphthyl (0.04g, 0.00bmmol), palladium acetate (I!) (0.009g, 0.04mmol) and a solution of M-benzylpiperazine (0.21g, 1.2mmol) in toluene (2ml) are placed in a round-bottom flask equipped with a condenser, with a magnetic stirring in a nitrogen atmosphere. The reaction mixture is heated at 85923 overnight, cooled, diluted with ethyl acetate and washed with water (three times) and saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed (0.24 g, 65 DCM/ethyl acetate (8:2)) to give the desired product (0.075 g). And C-M8: MN.- -346./H NMR (Z36OMHC, 5 1/million) DMSO

Ob: 1.37 (t, 71H), 1.67 (rgovzva a, 1H), 1.80 (t, 1H), 2.58 (0, 1H), 2.84-3.00 (i, 2H i t, 1H), 3.81 (rgoavy a, 1H), 4.40 (i, 2H), 7.12 (i, 1), 7.20 (t, ЗН), 7.26-7.37 (t, YAN ia, 1), 7.5 (a, 1H).

Example 14. 1-(6-oxo-5,6-dihydro-4H-imidazo|4,5,1-III)Yquinolin-2-yl)-4-phenyl-4-piperidinecarboxamide (K1,

K2, K2 - H, KZ is SOMN", KA - phenyl, X - C, p-t-1) (compound 43) 14.1. Compound of formula (1): 4-phenyl-piperidine-4-carboxamide

This compound is obtained by the synthesis described in the literature (Vioogd. Med. Spet. I ey. 7(19), 1997, 2531-2536). 14.2... 1-(6-oxo-5,6-dihydro-4H-imidazo|4,5,1-i|)quinolin-2-yl)-4-phenyl-4-piperidine-carboxamide

ZOOmg of compound (II) (item 1.17), bml of DMF, 7Omg of potassium fluoride, O0.2ml of 2,β-lutidine and 51Omg of compound (II), 7/0 described above, are introduced into a 50-milliliter three-necked flask under nitrogen. The mixture is stirred for 4 hours. at 1402C and evaporated under high vacuum. The residue is chromatographed on silica gel (70-200 μm) with a mixture of 295 methanol in DCM. The obtained product is recrystallized from a minimum amount of hot acetone and 27 Ωg of white crystals are obtained. The NMR spectrum corresponds to the desired product: "H NMR (200 MHz, 5 1/ml) DMSO Ob: 2.0 (t, 2H), 2.5 (t, 2H), 3.0 (i, 2H), 3.2 -3.8 (t, 4H), 4.45 (i, 2H), 7.0-7.5 (t, TON).

Example 15. Dihydrochloride of 1-(6-oxo-5,6-dihydro-4H-imidazo|4,5,1-III)quinolin-2-yl)-4-phenyl-4-aminopiperidine (KI, К2, К2 are H, KZ - MH", KA - phenyl, X - C, p-t-1) (compound 46) 4 ml of a concentrated aqueous solution of hydrochloric acid is added to compound 42 from the table (0.53 g, 1.21 mmol), prepared as it was described above and previously dissolved in 5 ml of methanol, and subjected to magnetic stirring at room temperature for 30 minutes. The mixture was concentrated under vacuum, the residue was taken up in absolute ethanol and evaporated to dryness to give the desired compound as a solid (0.45 g). "H NMR (200 MHz, 5 1/ml) DMSO 06: 2.4-2.8 (t, 4H), 3.1 (i, 2H), 3.7 (t, 2H), 4.2 (t , 2H), 4.8 (, 2H), 7.4-7.8 (t, 8H), 9.0 (v, 2H).

Example 16. 2-I4-(4-hydroxyphenyl)piperazin-1-yl|-4,5-dihydroimidazo|4,5,1-i)quinolin-b-one (BI, B2, B» is 2 H,b3 is-, X - M, BA - 4-hydroxyphenyl, p-t-1) (compound 71) at 16.1. Ethylene ketal 2-chloro-4,5-dihydroimidazoi|4,5,1-i)quinolin-b-one

A solution of the intermediate item 1.1 (0.6g, 2.9mmol) in 1,2-dichloroethane (1Oml), ethylene glycol (0.216g, 3.49mmol), p-toluenesulfonic acid (0.01g) and trimethylorthoformate (0.372g, 3 .49 mmol) are introduced into a round-bottomed flask equipped with a condenser, with magnetic stirring, and 1 mL of 1,2-dichloroethane is added. The mixture is kept under reflux for 24 hours, the same amount of reagents are added (ethylene glycol, p-toluenesulfonic acid and trimethylorthoformate) and the mixture is heated for another 8 hours. After evaporation of the solvent, the residue is taken up in ethyl acetate, washed with a dilute solution of sodium carbonate and water, the organic phase is dried and evaporated to dryness. The residue is chromatographed on silica gel with gradient elution (pure DCM with DCM/ethyl acetate (96:4) and the desired compound (0.54g, 7490) is obtained. MW. 5251.

From 16.2. Preparation of ethylene ketal - 2-I4-(4-benzyloxyphenyl)piperazin-1-yl|-4,5-dihydroimidazoi|4,5,1-iDhinolin-b-one

Intermediate No. 16.1 (0.54g, 2.1bmmol), THME (3ml), lutidine (277mcg, 2.3v8mmol), cesium fluoride (0.328g, 2.1bmmol) and 1-(4-benzyloxyphenyl)piperazine (0.725g) , 2.3 vmmol) are introduced into a flask with a rounded bottom, equipped with a condenser, with magnetic stirring. The reaction mixture is heated at 1009 °C, lutidine (ZOOmkl, 2.57 mmol) is added and heated at 1209 °C for 8 hours. The mixture is cooled, water is added and extracted twice with ethyl acetate. The organic phases are washed twice with water, dried over sodium sulfate, filtered and concentrated. The residue is purified twice by chromatography on silica gel with a gradient elution (DCM/ethyl acetate with a gradient from 90:10 to 40:60 and DCM/ethyl acetate with a gradient from 0:100 to 95:5) to give the desired compound contaminated with about 5095 ketone formed hydrolysis of the ketal function (0.365 g). And C-M5: 75 MN -483, MN. -439. and 16.3. Preparation of ethylene ketal co 2-I4-(4-hydroxyphenyl)-piperazin-1-yl|-4,5-dihydro-imidazo|4,5,1-quinoline-b-one

A mixture of the compound of Example 16.2 (0.365 g), ethanol (bbml), DCM (approximately 0.5 ml), and 1095 palladium on carbon (0.04 g) is placed in a round-bottomed flask equipped with a condenser, with magnetic stirring in an atmosphere of -k 70 of hydrogen for 17 hours. at room temperature. After filtering and evaporating the solvent, the residue is chromatographed on silica gel (gradient from DCM to DCM/methanol (94:6)) and the desired product (0.132g7) is obtained. "YAN NMR (300 MHz, 5 1/million) DMSO Ob: 2.2 (i, 2H), 3.13 (t, 4H), 3.46 (t, ZN), 4.08-4.20 (t , 4H), 4.21 (i 2H), 6.68 (ad, 2H), 6.86 (aa, 2H), 7.04 (t, 2H), 7.32 (t, 1H), 8, 91 (8, 1H). 16.4. Preparation of 2-|4-(4-hydroxyphenyl)piperazin-1-yl|-4,5-dihydroimidazo|4,5,1-yi)quinolin-b-one 2-I4- (4-hydroxyphenyl)piperazin-1-yl|-4,5-dihydroimidazo|4,5,1-yquinolin-b-one (0.055 g, 0.14 mmol) (F; dissolve in 1 ml of THF and add 3.5 ml of aq. of a 590% solution of hydrochloric acid

GI magnetic stirring 16bh. at room temperature and 2 hours. at 5020. After diluting with water, the mixture is basified with sodium bicarbonate, extracted twice with ethyl acetate, and the organic phases are dried over sodium sulfate. After the usual treatment, the residue is purified by chromatography on silica gel (gradient - from DCM to DCM/methanol (94:6)) and the desired product is obtained (0.027g, 5595). "H NMR (500 MHz, 5 t/ml) DMSO O6; 2.99 (i, 2H), 3.13 (t, 4H), 3.53 (t, 4H), 4.47 (I, 2H) , 6.67 (a, 2H), 6.85 (9, 2H), 7.15 (Her, 1H), 7.34 (a, 1Hn), 7.60 (a, 1H), 8.88 ( 5, 1H).

Example 17. 2-(4-(4-fluorophenyl)piperazin-1-yl|-4,5-dihydro-9-methylimidazoi|4,5,1-i||-quinolin-b-one (KI - 9- SN»U,

K2, Kg is H, KZ is -, X - M, K4 - 4-fluorophenyl, p-t-1) (compound 84) 65 Intermediate p.1.4 (0.2g, 0.907mmol), THME (2ml), lutidine (0.11bml, 0.998mmol), cesium fluoride (0.138g, 0.907mmol) and 4-fluorophenylpiperazine (0.180g, 0.998mmol) were placed in a round-bottomed flask equipped with a condenser under magnetic stirring. The reaction mixture is heated at 1402 °C. and after cooling, add water and extract twice with ethyl acetate. The organic phases are washed twice with water, dried over sodium sulfate, filtered and concentrated. The residue is chromatographed on silica gel (gradient - from pure DCM to DCM/methanol (98:2)) and the desired compound is obtained as a solid (0.206g, 62965). "H NMR (500 MHz, 5 1/million) DMSO O6: 2.50 (in, ЗН), 2.97 (I, 2Н), 3.28 (t, 4Н), 3.54 (t, 4Н), 4.45 (, 2H), 7.05 (t, 5H), 7.29 (a, 1Hn).

Example 18. 1-I4-(4-fluorophenyl)piperazin-1-yl|-3-methyl-8,9-dihydro-7H-2,9a-diazabenzo|sa|)azulen-b-one./- (K1 - 3-CH3, K2, K2 is H, KZ is -, X - M, K4 - 4-fluorophenyl, p-2, m-1) (compound 85) 1-chloro-3-methyl-8,9-dihydro -7H-2,9a-diazabenzo|syaa|azulene-b-one (0.2g, 0.852mmol), THME (2ml), lutidine 70 (0109ml, 0.937mmol), cesium fluoride (0.130g, 0.852mmol) and 4 -Fluorophenylpiperazine (0.169g, 0.937mmol) is introduced into a round-bottomed flask equipped with a condenser, with magnetic stirring. The reaction mixture is heated at 140922 C for 5 hours. and after cooling, add water and extract twice with ethyl acetate. The residue is chromatographed on silica gel (gradient - from pure DCM to DCM/methanol (60:40)) and the desired compound is obtained as a solid (0.137g, 42965). "H NMR (500 MHz, 5 1/million) DMSO 06: 2.20 (t, 2H), 2.53 (z, ZN), 3.04 719 (t, 2H), 3.30 (t, 4H) , 3.40 (t, 4H), 4.25 (t, 2H), 7.07 (t, 5H), 7.61 (d, 1H).

Example 19. 2-(4-(4-fluorophenyl)piperazin-1-yl|-4,5-dihydro-7-methylimidazoi|4,5,1-i||-quinoline-b-0n (KI - 7- SNU,

K2, Kg - H, KZ is -, X - M, K4 - 4-fluorophenyl, p-t-1) (compound 83) 2-chloro-4,5-dihydro-7-methylimidazo|4,5,1- iYiquinolin-b-one (0.245g, 1.tmmol), THME (2.5ml), lutidine (0.161ml, 1.21mmol), cesium fluoride (0.167g, 1.1mmol) and 4-fluorophenylpiperazine (0.219g, 1 ,1 mmol) are introduced into a round-bottomed flask equipped with a condenser, with magnetic stirring. The reaction mixture is heated at 14020 for 2.5 hours. and after cooling, add water and extract twice with ethyl acetate. The residue is chromatographed on silica gel (gradient - from pure DCM to DCM/methanol (60:40)) and the desired compound is obtained as a solid (0.26g, 6595). "H NMR (500 MHz, 5 1/ml) DMSO Ob: 2.59 (in, ZN), 2.98 (Hii, 2H), 3.26 (t, 4H), 3.49 (t, rya AN) , 4.42 (I, 2H), 6.94 (y, 1H), 7.05 (t, 4H), 7.50 (a, 1H).

Example 20. 2-(4-(4-fluorophenyl)piperazin-1-yl|-4,5-dihydro-8-methylimidazoi|4,5,1-yl|-quinolin-b-one (KI - 8-CH »z, (o)

K2, Kg is H, KZ is -, X - M, K4 - 4-fluorophenyl, p-t-1) (compound 82)

This compound is prepared, as in Example 19, from 1/2 of a mixture of 2-chloro-4,5-dihydro-8-methylimidazo-|4,5,1-i|)quinoline-b-one and c 20 2-chloro-4 ,5-dihydro-7-methylimidazo|4,5,1-yquinolin-b-one. After chromatography on silica gel, two successive crystallizations give the desired isomer contaminated only by 495 of another isomer (0.053 g, yield of the good isomer - 4895). "H NMR (500 MHz, 5 1/ml) DMSO 06: 2.40 (in, ЗН), 2.98 (I, 2Н), 3.26 (t, 4Н), 3.55 (t, 4Н), s 4.45 (I, 2H), 7.06 (t, 4H), 7.18 (v, 1H), 7.44 (8, 1H).

Example 21. 2-I4-(4-fluorophenyl)piperazin-1-ylI|-4,5-dihydro-7-methoxyimidazoi|4,5,1-yI-quinolin-b-one (К1 ОО - с з5 7- OSNU,K2, K2 is H, KZ is -, X - M, Ka - 4-fluorophenyl, p-t-1) (compound 81) h-

This compound is prepared as in Example 19 from 2-chloropiperazin-1-yl-4,5-dihydro-7-methoxyimidazoi|4,5,1-quinolin-b-one (2995). "H NMR (500 MHz, 5 1/million) of DMSO

O6: 2.89 (I, 2H), 3.26 (t, 4H), 3.44 (t, AN), 3.81 (z, ZN), 4.36 (i, 2H), 6.79 (a, 1H), 7.06 (t, 4H), 7.58 (y, 1H). "

The following table illustrates the chemical structures and physical properties of the compounds of the invention of the general formula 70 (I). Depending on whether n-1 or 2 in this formula, the two compounds of formula (I) have different numberings of atoms on the benzimidazole nucleus. ц In this table: "» NOI - hydrochloride, SEZSO»5H - trifluoroacetate salt, and "-" represents the compound in free form,

Me, EI, n-P' and IVy represent, respectively, methyl, ethyl, n-propyl and tert-butyl groups,

Bp and RA represent benzyl and phenyl groups, respectively, and unless otherwise indicated, NMR corresponds to proton NMR and measurements were performed in 46-DMSO. " and 7 mean measurements, respectively, at 36 MHz and at 5 B000 MHz. If such designations are absent, it means measurements at 200 MHz. (o) Table - 50 syu"

Ф) име) 60 b5 v , i n dz 1 Oh, what are these schi rek lush

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I other), 7.32 (a, Kk, 7.59 (4, other)» 17 yin |v |k (/ 1 3.1 (B, 28), 3.29 (t, YAN), 3.58 (sh, 48), 4.50 18, 28), 7.05 (t, 4B), 7.17 (i, 1H1, 7.35 Id, v | yin), 7.62 18, 18)" with (o) she (vi va (vab va (mo Them Daste|vyame shko zo 2.20 (m, 2H), 2.40-2.60 (w, ZN), 2.90 (B, 28), - 3.05 (t, ZN), 3.65 44, ZM), 4.20 (t, 2NI, 7.20 so

Y (w, zn), 7.65 (4, 18), 7.70 (4, 18)» ch zv s 1 1.10 (4, 18), 1.20 (w, 48), 1.60 (4, 18), 1.80 sh (4 , 48), 2.20 (8, 28), 2.30 (in, 18), 2-70 (t, 28), 7.20 (Kk, others), 7.65 (4, 18), 7.70 (3, 18)" " K 112 1.95 (i, 28), 2.239 (v, ZN), 2.56 (dsh, 2ShK, 2.74 n- - (y, 3KR, 2.99 (5, 28), 3.73 (t, 4H), 4.49 (g, o ZN), 7.08 (p. 18), 7.22 (a, 15), 7.43 (8, 1n)" according to In KIN 1 11 3.01 16, 9H), 3.29 (Bkova is, 4H), 3.58 (Bgogy

Swedes n, 4H), 4.45 (w, 2H), 5.98 (0, ЗН), 7.16 (5, o) | 11). We eat them (in |mo| sin Tyame or, 7.18 (E, Z), 7.37 (4, 18), 7.63 (3, 1H), 8.20 (a, a)" 24 v 1 4 Z ansi 388, zn ), 3.08 (6, 2H), 3.27 (m, 228), 3.55 (m, u tone) 3.72 (t. 298), 4.14 (t, out), 4.59 (B, 2H), 7.35 (b, B, 7.53 (4, IB), 7.75 16, 18), 11.42 (in, ZU

Be 1 about fans | rovvepoe ob Z sopboshtkv, -70/30: 1.32 (2, ZB), 2.31. (b, 0.68), 3.08 (w, 1.4n), 3.19 (c, 28), 3.60, 3.74, 3.80, 4.12, 4.24 (shepu khiisiriekn, VNU, 4.35 (B, . O.BN), 4. (5, 3.4), 7.36 (g, 1.41), 7.50 (t, 0.9NI, 7.73 (4, 0.78), 11.28 (8, 0.7), 11.55 (8, 0.3)" 26 a-vh (M oЙ1 |1 |one1 10.94 (6, zn), 1.78 (p, 2H), 3.08 (p, 48), 3.28 (t,

ОН), 3.62 (3, 29), 3.88 (sh, 28), 4.95 (х, 28), 4.68 (с, НУ, 7.49 (5, ЧО, 7.50 (8, 18), 7.76 (8, IV ), 11.65 (in, 16)" se

So TINSHЇv |yuCyu iv (le |x (vsya (vnyamefivv o G 11111111 with |n |n |n -some |m |1 Rgevnpse OE 2 soproshnete, «50/40: 1.86 (t, 0.8Н), 1.54 (p . - (Shl, 18), 7.6 il 18)» so 32 n va 1 |1 1.23 (4, ZNU, 3.19 (m, 18), 3.32 (p, 48), 3.57 (M, sch 48), 4.11 (B . 18), 4.53 (84, 18), 5.83 (B. IN), 7.01 i- (a, sn), 7.37 (B, 1), 7.26 (B, 28), 7.37 (a, 1K, and 7.51 ( 8, 1)" " 33 - 1 1 1.22 (2, ZN), 3.18 (y, IIA), 3.52 (t, YAN), 3.58 (t, Z xz" (4, 1y), 7.17 (B, 18) . 8, 18), 7. so and t, IN), 7.62 (8, IN), 8.06 (y, IN), 8.39 (v, IN" a yu syu"

Ф) kobo 65 ee (vi (vana |v (vh all vyamefiyu 17 - iv with 1 2.2 (p, 28), 3.05 (i, 28), 3.30 (t, 48), 3.35 y (w, 4H), 4.25 (t, 28), 6.8 (b, 18), 7.9 (8; 28), 7.2 (2, 18), 7.25 (4, 18), 7.3 (4, 18), t,b 14, etc.), 7.65 (0, 18)" 7 vk o |n si 1.6 (in, bH), 2.9 (6, ZNR, 3.35 (n, 4K), 4.40 (B, 2), 7.10 (E, 15), 7.3 (4, 18), 7.55 (8,

In) 9 1" but |vv s: |: 1.95 (sh, 48), 2.85 (t, 18), 3.20 (t, 45), 4.0 (4, zone, 4.5 (0, 28), 7.2-7.4 ( t, 78), 7.55 (8. 18) 2018 i |-- |n s 1 |; 1.75 (5, 48), 2.3 (yu, 18), 2.95 (m, 48), 3.80.

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Phi ich - Art. | R s 1 3.1 (w, 28), 3.3 (n, 28), 3.0 (B, 2SHІ, 3.3-3.5 ish, ВН) Y h - s 42 V -Shn- | R p 11 11 1.1 (5, ZNU, 9 (pieces, 9H), 2.5 (sh, 28), 2.98 (b, from life 28). 3.2 (t, 2M)U, 3.70 (t, 2), 4.4 ( is, ZV),

M y M YA Y y An m (n, 48), 4.45 (B, 2NI, 7.0-7.5 (t, 10H) so no|Yino o |-mn- | vvs her 2.0-2.6 (t, 4), 3.1 (B, 28), 3.4 (t, 38), 3.8 a ty som (8, 28), 4.5 (B, 28), 5.5 (5, 28), 6.5 (v, s» M prom (F 1.2-2.3 (m, 128) 3.0 (m, ZY), 3.2-3.4 (t, "4H8), and 4.2 (4 , 2n), 4.65 5, 2ShR, 7.4 (B, 18), 7.6,

IZ, Z), 7.8 (4, 18) "b |k -shcn" | Ri c 1 11 |znsz |5.4-3.8 (c, 8), 3.1 (5, 2H), 3.7 (t, 28), 4.2 70 (t, 28), 4.8 (B, ZM), 7.4-7.8 (t, 8H), 9.0 (in,

In) -47 - s | 1.5-2.0 (sh, VN), 3.0 (t, 48), 3.2-3.6 (t, 5H), 4.1 (a, zn), 4.6 (B, 28), 7.3 (E, IN), 7.5 ( 4, iz I, 7.6 (4, 1) - Me, «v |k - s | 1 1.5-3.0 (sh, 108), 8.1 14, 2H), 2.8-3.0 (sh, 2). 7.4 (5, 18), 7.6 (a, 18), 7.7 (a, 18) 49 in and 1.19 (8, 6H), 3.33 (5, 48), 3.55 (t, 48), 4.29 (in, 2) . zha |v (mo, hv sele|vyaMR. niv

Bo "/ shchi 1 11 Izns 13.06 (5, ZNR;, 3.63 (t, 4H), 3.84 (t, 4H), 4.65 so | (w, 28), 7.30 (a, 28), 7.25 (8, 2H) . , 8n), 4.47 (6, 2), 7.16 ich- (84, 1), 7.32 (44, 2), 7.35 (y, 18), 7.55

I (av, zn), 7.52 (4, in); MMK1:51.6 (t, 18)" " - s (t, 28), 4.48 (5, 28), 7.16 (84, 18), 7.36 (4, xz" 1n), 7.47 (d, zn)" 53 | others 3 |1 1» Ov (in, ZM), 1.30 (t, 6H), 1.53 (t, 28), 2.37 (b, 2n), 3.01 (5, 23), 3.41 (sh, 2H), 3 ,44 (in,

V. 28), 3.64 (w, 4n), 4.47 (B, ZNU, 7.15 (y4, t yn), 7.35 (4, 1), 7.61 (8, 18)" (ee) shu 20 syu

F) name) bo 65 ze. vi Ivaf|zhae|yua |ve same (vsiyavfinyamefnyo 54 |V men ikh b. s 1 Vkevepse ОЙ 2 sopEOutschega. 1.21 (a, ZN), 1-74 y | dya t, 2H). 1.94 (t, YAN), 2.14 (y, ZM), 2.80 (iv,

BA IN), 3.13 (t, ZN), 3.95 (w, 28), 4.11 (B, 18), 4.58 (t, 18), 7.15 (44, 18), 7.35 (sh, ЗB), 70 and 7.59 ( 4, 18), 11.57 t, 18)» 55 I n n VII Rtevepse oyi 2 soptotshekya. 1.75 (w, 2H), 1.95 t. (p, 28), 2.12 (285 40760, ЗB), 2.23 (t, NO), /5 | 2.79, (2t 40/60, 1H), 3.05 (t, 4H), 3.65 (t, 2ni, 4.24 ish, 23), 7.15 (04, 18), 7.36 (in, 18), 7.68 (t, 24) , 11.54 128, 40/60, 1H)» 56 In | - pa 1 |; 2.58 (5, 2n), 2.62 (m, 48), 2.78 (B, 28), 2.98 7 (b, 28), 3.42 (t, 48), 4.43 (B, Y), 7.14 (49, 1H ), 7.19 (t. zn), 6.51 y, 28), 7.15 (88, 1), 7.33 «- y ish, YAN), 7.35 (8, IN), 7.61 (8, m so 58 in -U shchi 1 | 2.79 (B . -

I , yin), 7.35 (y, 18), 7.60 a, re» 59 In - in 1 | 1.69 (sh5, 18), 2.13 (8, 68), 2.22 (Ж, 2НИ, 2.22 (B, « du 28), 3.00 (B, 2Н), 3.27 (t, YAN), 3.55 (t, 48), 4.28 - in s (b, 28), 6.04 (8, ZON), 7.15 (8, 18), 7.35 (4, 18), 7.4Ab 4, ОН), 7.61 (6, 38) 9.68 ( in, SHHA" I 18 o u-e|n |i 1 1.39 (5, ZSh, 3.00 (5, 28), 3.25 it, 48), 3.55 (p,

She 4H), 4.48 (B, OH), 6.94 (4, 38), 7.15 (8, 18), 7.35 o (3, 1), 7.44 (8, 2), 7.61. 8, 19) . 7.6 (t, 70) 62 m y; c1 | |- 1.6-1.8 (t, 2Y), 2.1-2.3 (t, 28), 2.9 her, ОН), 70 сх, | 3.3-3.5 (B, ЗН) . 7.6 (shchu 28) 9 va |n so 1 |i |z 1.2-2.4 (t, 88), 2.6-3.7 (t, 108), 4.2 (4,

SsyuesoOz2n), 4.7 (Kk, NN). 7.4 her, ZNI, 7.6 (a, 1H), 7.5 (a, 18), i. (a, on) 65 - eyelashes 3.01 1, 2p), 3.20 (sh, 4H), 3.59 (t, 4H), 4.48.

Э (иЭ, 2Н), 7.01 иш, 18), 7.14 (ж, 4Н), 7.36 (4, ин), 7.69 14, 18) - s |n.|m Gka|vy|yu m /|x |v salt |vyam o vv |n |n ich Fu 1 | 1 |- 3.01 (E, ZN), 3.15 (n, 48), 3.58 (t, 48), 4.48 (Zh, 28), 7.03 (t, IN), 7.15 (m, 28), 7.24 (in , | o 20 i i 1H), 7,365 (y, 18), 7.52 (4, 1H) shi 67 |V vn |n 1- U 1 11 3.01 4, 28), 3.54 (t, 48), 3.76 (sh , 48), 4.49 t (E, 2n), 7.15 (B, 18), 7.35 (y, 1H), 7.51 (a, so 18), 7.88 (4. 1H), 8.13 (4, 18), 8.39 (v. TSI s vv ii: 2.56 it, 48), 2.96 (ich, 2H), 3.43 (t, 4), 3.59 - iv, UNR, 4.41 (5, 9H), 7.13 (6, 183. 7.39 (8, 18), 7-35 (9, 28), 7.58 (4, 18), 8.59 (8. SYA) « - ke 2.32 them, mass media, 3.00 (w, 2M), 3.51 ish, 4M), 3.56 - s sn, (w, 48), 4.49 5, ZN), 6.55 (4, 18), 6.67 (48, with 1), 7.15 15, 128), 7.35 (4, 18), 7.45 (u , and 18), 7.61 (6, IN) . -1 ko (ee) - 50 syu (F) ko bo b5 ek Yvi Zvaf|vab vo Zveo Zh asyayuervyav fin 1 tya 1 |i 1.43 (v, 2), 5.50 (j, b), 1.62 (t, 2H), 1.74 (t, 28), and 2.49 (y 18), 2.62 (5, 48), 2.97 (p, 28), 3.37 (lu 49), , 4.41 (5, 2), 7.19 (Kk, 18 ), 7.39 y, VR, 7.57 (a, eni ti |n F im |1 | 2.99 (B, 28), 3.13 (0, 48), 3.53 (sh, 48), 4.47 (B, 28), 170 5.67 (8, 28), 5.85 (4, 28), 7.15 (x, 18), 7.34 (8, 18), 7.50 (b, yin), 8.88 (c, 18)

In tires 75 6.92 (p, 28), 7.14 (B, 18), 7.39 (t, 28), 7.58 (3, 15) 48), 3.67 (w, VNU, 4.20 (sh, zv), 4.67 (t, zm), 7.30 and b), 7.53 (y, 18), 7.68 (t, IN), 11.37 (n, yin) 7a i |n (in GK 1.47 (sh, 29), 1.60 (shu ZA), 2.36 (5, 2), 2.50 (tu, 48), ' 2.60 (5, ZM), 2.98 (B, ZZh), 3.39 (lu 48), 4.43 (in, ZB), 7.14 (k, 18), 7.16-7.30 (1, BN), 7.33 (4, 18), 7.58 (8, sch

And hey) that. (va va |kab|(yua Ivah fa sil ivyame vi Z 75 |n - t and 1.79 (m, ZK), 2.35 (t, ZM), 2.54 (sh, 4H), 2.54 o - y (s, 2M), 2.98 (s, 2H), 3.21 (t, 48), 4.42 (Kk, -

STILL Not 2n), 7.14 (is, 18), 7.26 (4, 28), 7.33 (4, iv), so 7.58 (4, 1B5y, 8.45 (8, 20) | sch 3576 | |n -KE; 1 1 |at 1.6-2.2 (t, 4H), 3.0 (5, 28), 3.5 (m, ЗН), 4.1 и- cha on), 4.65 (s, 2Нх, 7.4 (s, yin, 7.56 (4, yin) . (EE, 2H), 7.2 (Zh, TYA), 1.3 with (t AN), 7.6 (4, IB), 8.5 (6. ZN) 7v H z|n |z | 1.39 ish, 1H1, 1.72 (t, 28), 1.83 (t, 2H), 2.12 (B, 38), 2.19 (m, 18), 2.64 (t, 48), 2.78 (m,

B 28), 3.97 (, 28), 3.39 (w, 4), 4.41 (KE, ЗB), where 7.13 (SE, 18), 7.32 (3, 100, 7.56 d, 18) (ee) tsu 5 syu ( F) ko bo b5 no. |at the vases of Tsiam|nyu |on oh v st viam | niv t In n nd o) 11 3.00 (W, 25), 3.20 (t, 48), 3.55 (1, 48), 4.47 (Kk, 2), 9 5.03 (v, ZM), 6.94 sha, 48), 7.15 12, IN), 7.37 (in, 6H), 7.60 (8, 19) and 1 | 1.76 (y, 38), 2.34 (B, 28), 2.53 (t, 4), 2.61 (B, ZSh), ! 70 2.97 (5, 28), 3.39 (p, JAN), 4.42 (5, 28), 7-14 (t, 28), . 7.91 ish, 2), 7.97 izh, 2H), 7.32 (a, 18), 7.57 (y, 1) and sha ny and sh ev and o. Хе Хще те Х Х 4.36 (6, 28), 6.79 (4, 10, 7.05 (tu, 48), 7.58 (8, 11) vz er pt tr 4.45 (8, 28), 7.06 (tu 48), 7.18 (v, 18), 7.44 (v, 18) ee sy and shchi sv and shchi y Shchi shchi and sh 20. 4.43 (6, 728), 5.94 (0, 18), 7.05 (m, 48), 7.50 ( 4, 28). 9-Me H (y 1 |1 2.50 (8, ЗН), 2.97 (5, 2M), 3.98 il, 4), 3.54 ish, 48), 4.45 (Ж, 2Н), 7.05 (t , 58), 7.29 (4. 5, ZN), 3.04 (m, 28), 3.39 Mk (t, 41), 3.40 (shsh, 4H), 4.25 (t, 28), 7.07 (w, "- vi, 7.81 a, 1n; (ge) n -Щ- |В s 1 1 2.2 them, FP), 2.4 (m, 2), 3.0 (t, 2H), 3.7 (8, mech en). 3.4 (shcha, ZNA), 3.5 her, IN), 4.5 (t, 2H), Y s sg 4.7 (t, ZK), 7.5 (B, 18), 7.75 (4, 38), 7.9 - (a, 18) 87 n o rnyayum 111 Zh.10 (w, 98 ), 1.30 (c, 98), 1.65 t, 2H), 2.4 « ii, 1H), 2.60 im, b), 3.0 (2, 28), 3.4 «m, - s Yani, 3.95 (m, 2H), 4.4 (c, 28), 7.1 (b, IN),

M 7.25 a. 18), 7.6 (8, 18) and 88 1 | 1 2.0 isch, OH), 2.4 (sh, 2H), 3.0-3.3 (t, 2H), 3.5 (t, ЗН) 4.0 (m, 9H), 4.7 (t, 2H), 7.45 (B, 7in» , 7.60 (8, other), 7.8 (y, 18) ko so no ), 2.30 (w, 28), 2.75 (8, ZN), 3.2 s» Me SESOJ El, 28), 3.5 (t, 18), 3.45 (t, 28), 4.2 (her, 28) . . 18), 7.5 (4, 18), 7.7 4, 1NO 60 her 9: In En |n o | he - blues 1.65 (4, 2H), 2.4 (p, 2H), 3.10 (5, 2H), 3.5 (t, 28), 3.8 (v, 28), 4.5 (b, 2H), 5.45 (8 .

The compounds of the invention were subjected to pharmacological tests to determine the inhibitory effect on RAKR or poly(AOR-ribose) polymerase.

The compounds of the invention were subjected to the following tests:

The effect of the compound on the enzymatic activity of RAKR

Recombinant human RAKR-1 (PRAKR-1) is produced by cells 59 using a baculovirus expression system (Sipeg et al., Sepe (1992), 114, 279-283). The enzyme in a partially pure form was obtained from the cell extract after precipitation with 70956 ammonium sulfate. The obtained solution of PRAKR-1 was able to generate 0.5-0./nmol of nicotinamide from MAO. under the standard test conditions described below. The compounds to be tested were dissolved in an incubation medium containing 50 mM Ttgiv-HCl, 10 mM MOCI 5, 20 mM zinc acetate, 1.5 mM dithiothreitol, 0.2 µg histone, and 0.1 µg oligonucleotide (ZSAATTSS) per 10 µl , in the presence of partially purified PRAKR-1, buffered to pH8. The enzymatic reaction was initiated by adding

MYU (0.2 mm) and observed at room temperature for 20 minutes. The reaction was stopped by adding

NSU, (1.2M) at 420. After centrifugation, the supernatant liquid was analyzed by HPLC (column Zpapdop OPgarase 75 C8). Isocratic elution was carried out using a phosphate buffer (0.1 M) (pH4.5) containing acetonitrile, which was injected at a rate of 1.25 ml/min. for two weeks The formed nicotinamide was detected by measuring the ultraviolet absorption (265 nm) of the eluate with quantization relative to the peak due to the external standard nicotinamide (2 nmol). The residual activity of PRAKR-1 was measured in the presence of the vinazode compound at various concentrations and compared with the corresponding data obtained in its absence. All measurements were performed at least twice, and ICvco values were calculated using a sigmoid dose-response curve.

This test showed that the most active compounds had ICs in the range of 5-500 nm.

In addition, the compounds of the invention acted on RAKR-2, and the most active compounds for this enzyme also had

ISvo Within 5-500NM.

Therefore, it was found that the compounds of the invention are selective inhibitors of RAKR, in particular RAKR-1 and RAKR-2. with

Thus, the compounds according to the invention can be used for the preparation of medical products, in particular, RAKR inhibitors. Such products can be used in therapy, in particular, for the prevention or treatment of myocardial infarction, cardiac ischemia, heart failure, atherosclerosis, restenosis after RTS or bypass surgery, cerebral ischemia and cerebral infarction caused by ischemia, trauma or thromboembolism, such neurodegenerative diseases, such as Parkinson's disease, Alzheimer's disease and Huntington's chorea, acute renal failure, in particular, of ischemic origin or after kidney transplantation, treatment of rejection after heart transplantation, accelerated atherosclerosis, inflammatory pathologies, - immunological disorders, rheumatoid diseases, diabetes and pancreatitis, septic shock , acute respiratory syndrome, tumors and metastases, autoimmune diseases, AIDS, hepatitis, psoriasis, vasculitis, ulcerative colitis, multiple sclerosis and myasthenia gravis. with

Therefore, the compounds of formula (I) according to the invention can be used for the preparation of medical food products suitable for the treatment and prevention of disorders associated with the RAKR enzyme.

Another object of the invention is the use of a compound of the formula (I), in which K1, K2, K2, K3 are H, X is C, p-t-1 and K4 is a 4-imidazolyl or 5-methyl-4-imidazolyl group, for the preparation of a medical product suitable for the treatment and prevention of disorders associated with the RAKR enzyme. "

The invention also relates to pharmaceutical compositions, the composition of which includes compound 8c of the invention as an active agent. These pharmaceutical compositions contain an effective dose of the compound of the invention and one or more pharmaceutically acceptable excipients. The specified fillers are chosen according to the desired "" pharmaceutical form and method of administration.

In pharmaceutical compositions according to the invention for oral, sublingual, subcutaneous,

For intramuscular, intravenous, local, intratracheal, intranasal, -I transdermal or rectal administration, the active agent of formula (I), or possibly a salt or hydrate thereof, can be administered in the form of unit doses in admixture with pharmaceutically acceptable excipients to animals and humans where for the prevention or treatment of the above disorders or diseases. Unit dosage forms include such forms for oral administration as tablets, capsules, powders, granules and solutions or suspensions, and forms for sublingual, buccal, intratracheal and intranasal, subcutaneous, intramuscular, intravenous and rectal administration. The compounds according to the invention can be applied in the form of creams, ointments or lotions.

The daily dose of the active agent can be from 0.1 to 1000 mg/kg for oral, parenteral or rectal administration. In some cases, smaller or larger doses and such doses may also be necessary

INCLUDED in the scope of the invention. Usually, the dose for each patient is determined by the doctor, taking into account the method of administration, weight and reaction of the patient. iF) When using a solid composition in the form of tablets, the active ingredient is mixed with a pharmaceutical co-filler, for example, gelatin, starch, lactose, magnesium stearate, talc, gum arabic, etc.

Tablets can be coated with sucrose, cellulose derivatives or other materials. Tablets can be made in various ways, for example, direct pressing, dry granulation or hot melting.

Preparations in the form of gel capsules are made by mixing the active ingredient with a diluent and pouring this mixture into soft or hard capsules.

For parenteral administration, aqueous suspensions, isotonic saline solutions, or sterile injectable solutions containing pharmacologically compatible dispersants and/or wetting agents such as propylene glycol or butylene glycol may be used.

Another object of the invention is a method of treating the above pathologies by introducing a compound of the invention or its pharmaceutically acceptable salt.

Claims (1)

2 Formula of the invention 1. Compounds of formula (1): M -y av (y, tyu t r nia I both Na), o K2 in which: K1 - hydrogen atom, C1-C4-alkyl group, halogen atom, nitro group or C1-C4 - alkyl group, K2 and kg are, independently of each other, a hydrogen atom or a C1-C4 alkyl group, X is a nitrogen or carbon atom, claim 1 or 2, t is 1 or 2, and when X is a nitrogen atom: KZ is a hydrogen atom or a C1-C4 alkyl group, and then the compounds of formula (I) include quaternary ammonium, or, alternatively, KZ is absent, and then the compounds of formula (I) include a secondary or tertiary amine, Ge KA - a hydrogen atom , C1-Cb-alkyl group, C3-C7-cycloalkyl group, C3-C7-heterocycloalkyl group, as (5) variant, substituted by C1-C4-alkyl group or -SOOK group, in which K is C1-Cb-alkyl group , the -(CHNo)p-heteroaryl group, in which p can have a value from 0 to 4, and the heteroaryl group is selected from pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, imidazolyl, and thienyl groups, and the specified heteroaryl group , as an option, can be substituted by a C1-C4-alkyl group, (ze) a heteroarylcarbonyl group, and the heteroaryl group is selected from furyl, pyridyl, -pyrimidyl, pyrazinyl, pyridazinyl and imidazolyl groups, a phenylcarbonyl group, and the phenyl group is, as an option, substituted by a halogen atom, (ee) (C1-Cb)-alkylcarbonyl group, ch group "СНо)рСООК, where p can have a value from 0 to 4, and K is a C1-Cb-alkyl group, phenylsulfonyl group, as an option, substituted by to the phenyl nucleus by a halogen atom, a trifluoromethyl group, a C1-C4-alkyl group, a nitro group or a C1-C4-alkyl group, or, alternatively, a "CH"o)p-phenyl group, where p can have a value from 0 to 4, and the phenyl group, as an option, is replaced by one to three groups independently selected from C1-C4-alkyl, nitro-, amino-, hydroxyl groups, halogen atom, trifluoromethyl group, C1-C4-alkyl group, (C1-C4)-Alkoxyphenyl fupa, C1-C4-alkylamino group, C1-C4-dialkylamino group, groups -МНОНО or groups -МНСОК, where КК is a C1-C4-alkyl group or a C1-C4-alkyl group, and this C1-C4-alkyl group, as an option, is replaced by a dimethylamino group, and when X is a carbon atom, then : ni KZ - hydrogen atom, group -MAE5Kb, group -MSH(B5)3", group -MNSOK?7, group -SOMNE5, group -SOK7, -MINSOMN" group, group -OH or group -CH.OH, KA - a hydrogen atom, - -(CH»)p-phenyl group, in which p can have a value from 0 to 4, and the phenyl group, as an option, is replaced by d) 1-3 groups selected, independently of each other, from C1 -C4-alkyl group, nitro group, amino group, halogen atom, trifluoromethyl group or C1-C4-alkyl group, co -(CHNo)p-heteroaryl group, in which p can have a value from 0 to 4, and the heteroaryl group is selected from - -o3i 270 imidazolyl group, optionally substituted by a C1-C4-alkyl group, pyridyl, aminopyridyl, pyrimidinyl, pyrazinyl or pyridazinyl group, or, in another variant, c» group -SNOHMK7KV, in which is equal to 0 or 1, provided that that when the CA is a group -МК7К8В, then КЗ is not one of the groups -МК5Кб6, -МНСОК7, -МНСОМН 5 and -ОН, K5 and Kb are, independently of each other, a hydrogen atom or a C1-C4-alkyl group, 52 K7 and K8 are independently of each other, C1-C4-alkyl or C1-C4-alkyl group, or they together Ge! form a saturated 5-7-membered ring, which, as an option, includes an additional nitrogen atom, and this ring is on a carbon or nitrogen atom, including the nitrogen atom to which K?7 and K8 groups are attached to form quaternary ammonium, as variant, can be replaced by a C1-C4-alkyl group or a group -SOOK", in which KK" is a phenyl or (C1-C4)-alkylphenyl group, except for two compounds in which K1, K2, K2, KZ YeeH,X -C,p-t - 60 1, and kA - 4-imidazolyl or 5-methyl-4-imidazolyl group, in the form of enantiomers or diastereomers, or mixtures of these different forms, including racemic mixtures, as well as in the form of bases or addition salts pharmaceutically acceptable acids. 2. The compound of formula (I) according to claim 1, which differs in that it contains: K1 - hydrogen atom, C1-C4-alkyl group or C1-C4-alkyl group, b5 KO - hydrogen atom or C1-C4-alkyl group , K2 is a hydrogen atom, X is a nitrogen atom, n equals 1 or 2, t is equal to 1 or 2, KZ is a hydrogen atom, and then the compounds of formula (I) comprise a quaternary ammonium, or alternatively, KZ is absent, and then the compounds of formula (I) comprise a secondary or tertiary amine, KA - hydrogen atom, C1-Cb-alkyl group, C3-C7-cycloalkyl group, a pyridyl, pyrimidinyl or pyrazinyl group optionally substituted with a C1-C4 alkyl group, a heteroarylcarbonyl group, where the heteroaryl group is a furyl or pyridyl group, 70 phenylcarbonyl group, where the phenyl group is optionally substituted with a halogen atom, (C1-Cb)alkylcarbonyl group, the group "CH2)pCOOR, in which p can have a value from 0 to 4, and K is a C1-Cb-alkyl group, phenylsulfonyl group, a phenyl group substituted by 1-3 groups independently selected from the C1-C4 alkyl group, 7/5 Nitro group, amino group, hydroxyl group, halogen atom, trifluoromethyl group, C1-C4-alkyl group, (C1-C4)-alkoxyphenyl group, (C1-C4)-dialkylamino group, -MHCNO group or -MHCOC group;, in where K is a C1-C4-alkyl or C1-C4-alkyl group, and this C1-C4-alkyl group is optionally substituted by a dimethylamino group, -(CH»)p-phenyl group, in which p can have a value from 0 to 4, -(CH»)p is a pyridyl group, in which p can have a value from 0 to 4, - (CH»)p-thienyl group, in which p can have a value from 0 to 4, (C3-C7)-heterocycloalkyl group, as an option, substituted by a C1-C4-alkyl group or a -SOOK group, in which Kk is a C1-Cb-alkyl group, or, in another version, sch K1 - hydrogen atom, K2 and kg are, independently of each other, a hydrogen atom or a C1-C4 alkyl group, (8) X is a carbon atom, n e 1 or 2, t- 1, co KZ - hydrogen atom, group -МК5Кб, group -М(К5)5", group -МНСОК?7, group -СОМНЕ5, group -МНСОМН", group -OH or group -СН.ОН, -- K4 - a hydrogen atom, a benzyl group, a phenyl group, as an option, substituted by 1-3 groups selected, e) independently of each other, from a C1-C4 alkyl group, a nitro group, an amino group, a halogen atom, a trifluoromethyl group or a C1-C4 - an alkyl group, c a heteroaryl group selected from an imidazolyl group, optionally substituted by a C1-C4 alkyl group, or - a pyridyl group, group - MK7K8, provided that, when KA is the group -МК7К8, then КЗ is not one of the groups -МК5Кб, -МНСОК?7, -МНСОМН 5 and -ОН, " K5 and Kb are, independently of each other, a hydrogen atom or a C1-C4 alkyl group, 7 and 28 are, independently of each other, a C1-C4-alkyl or C1-C4-alkyl group, or together they form (ЧО с a saturated 5-7-membered ring, which, as an option, includes an additional nitrogen atom, and on carbon atom or nitrogen atom, including that nitrogen atom to which K7 and K8 groups are attached to form quaternary "» ammonium, may, as an option, be replaced by a C1-C4-alkyl group or a group-SOOK", in which K" - phenyl or (C1-C4)-alkylphenyl group, with the exception of two compounds in which КИ, К2, К2, КЗ ЕН,Х - С, п - т - 1, and KA - either 4-imidazolyl, or - And 5-methyl-4-imidazolyl group, in the form of enantiomers or diastereomers, or mixtures of these different forms, including racemic mixtures, as well as in the form of bases or addition salts of pharmaceutically acceptable acids. (ee) 3. The compound of formula (I) according to claim 1 or claim 2, which differs in that it contains: tsu 5 KI - a hydrogen atom, a methyl or methoxyl group, KO - a hydrogen atom or a methyl group, c» K2 - a hydrogen atom, X is a nitrogen atom, n e 1 or 2, t - 1 or 2, KZ is a hydrogen atom, and then the compounds of formula (I) include quaternary ammonium, or, alternatively, KZ F is absent, and then the compounds of formula (I) include a secondary or tertiary amine, where KA is a hydrogen atom, C1-C4-alkyl group, C6-C7-cycloalkyl group, a pyridyl, pyrimidinyl or pyrazinyl group optionally substituted with a C1-C4 alkyl group, is a heteroarylcarbonyl group, where the heteroaryl group is a furyl or pyridyl group, a phenylcarbonyl group, where the phenyl group is optionally substituted with a halogen atom, (C3-C5)-alkylcarbonyl group, "СНо)рСООК group, in which p is 0 or 1, and K is a C1-C4-alkyl group, a phenylsulfonyl group, a phenyl group, substituted by 1-3 groups selected independently of one, from a methyl group, a nitro group, an amino group, a hydroxyl group, a halogen atom, a trifluoromethyl group, 65 Mmethoxy group, (C1-C4)-alkoxyphenyl group, dimethylamino group, -MNONO group or -MNHSOK group, in which K is a C1-C4-alkyl or C1-C4-alkyl group, and this C1-C4-alkyl group, as the variant substituted by a dimethylamino group, the group ""CHno)p-phenyl, in which p is equal to 1, 2, C or 4, the group ""(CH2o)p-pyridyl, in which p is equal to from 1 to C, the group -(CH" o)p-thienyl, in which p is 2, a Cb6-C7-heterocycloalkyl group, as an option, substituted by a methyl group or a -SOOK group, in which K is a C1-C4-alkyl group, or, in another option, K1 - hydrogen atom, K2 and K2 are, independently of each other, a hydrogen atom or a methyl group, 70 X is a carbon atom, p e 1 or 2, t 1, KZ is a hydrogen atom, group -МК5БЕ6, group -М(СНая)з ', group -MNSOK?7, group SOMNE5, group -MNSOMN", group -OH or group -CHNOOH, K4 - hydrogen atom, benzyl group, phenyl group, as an option, substituted by 1-3 groups selected independently of each other from of a halogen atom and a trifluoromethyl group, a heteroaryl group, namely, an imide the sol group is optionally substituted by a methyl or pyridyl group, the -МК7К8 group, provided that when КА is the -МК7КВ8 group, КЗ is not any of the -МАК5Кб, -МНСОК?7, -МНСОМН»» and -ОН groups, K5 and Kb are, independently of each other, a hydrogen atom or a C1-C4-alkyl group, K7 and K8 are, independently of each other, a C1-C4-alkyl group or together they form a saturated 5-7-membered ring, which, optionally includes an additional nitrogen atom, and this ring on the carbon atom or on the nitrogen atom, including the nitrogen atom to which the K7 and K8 groups are attached to form the quaternary ammonium, can optionally be replaced by a methyl group or a -SOOK group", in which K" is a (C1-C4)alkylphenyl group, Ha with the exception of two compounds in which КИ, К2, К2, КЗ Е Н,Х - С, po - т - 1, and KA - 4-imidazolyl or 5- methyl-4-imidazolyl group, o in the form of enantiomers or diastereomers, or mixtures of these different forms, including racemic mixtures, as well as in the form of bases or addition salts of pharmaceutically acceptable acids. 4. Compounds of formula (I) according to claims 1-3, which are selected from the group consisting of: co 1-(6-oxo-5,6-dihydro-4H-imidazo|4,5,1-iiiY)quinoline- 2-yl)-4-piperidinopiperidine, 1-methyl-1-(1-(6-oxo-5,6-dihydro-4H-imidazoi|4,5,1-yl)quinolin-2-yl)-4- piperidinyl|-piperidine, -- 2-(4--4-dimethylaminophenyl)piperazin-1-yl)4,5-dihydroimidazo-|4,5,1-i))quinolin-6b-one, ee) 2-I4 -(4-tert-butoxycarbonylaminophenyl)piperazin-1-yl)|-4,5-dihydroimidazo|4,5,1-i|Yquinolin-b-one, 2-I(4-(4-aminophenyl)piperazin-1 -yl)4,5-dihydroimidazo|4,5,1-yl)quinolin-b-one, c 2-(4-(4-acetamidophenyl)piperazin-1-yl)4,5-dihydroimidazo|4,5,1- i))quinolin-6b-one, - 2-(4-p-propylpiperazin-1-yl)4,5-dihydroimidazo|4,5,1-i))quinolin-6b-one, 2-(4-tert -Butyloxycarbonylpiperazin-1-yl)4,5-dihydroimidazolium|4,5,1-yl)quinolin-6b-one, 2-(piperazin-1-yl)4,5-dihydroimidazolium|4,5,1-yl) quinoline-b-one, « 2-(4-acetylpiperazin-1-yl)4,5-dihydroimidazo|4,5,1-i))quinolin-6b-one, 2-(4-(4-pyridyl)- piperazin-1-yl)4,5-dihydroimidazoi|4,5,1-yquinolin-b-one, - with 2-(4-benzi lpiperidin-1-yl)4,5-dihydroimidazo|4,5,1-i|)quinolin-b-one, c 1-(6-oxo-5,6-dihydro-4H-imidazo|4,5,1 -yl)quinolin-2-yl)-4-phenyl-4-piperidinecarboxamide, "» 1-(6-oxo-5,6-dihydro-4H-imidazoi|4,5,1-yl)quinolin-2-yl )-4-phenyl-4-aminopiperidine, 2-I4-(4-hydroxyphenyl)-piperazin-1-ylI4, 5-dihydroimidazo|4,5,1-i|)quinolin-6b-one, 2-I(4 -(4-fluorophenyl)-piperazin-1-yl)4,5-dihydro-9-methylimidazo|4,5,1-i))quinolin-6b-one, -I 1-(4-(4-fluorophenyl) -piperazin-1-yl|-3-methyl-8,9-dihydro-7H-2,9a-diazabenzo|sa|azulen-6b-one, 2-I(4-(4-fluorophenyl-)piperazin-1- yl)4,5-dihydro-7-methylimidazo|4,5,1-i))quinolin-6b-one, di 2-I(4-(4-fluorophenyl)-piperazin-1-yl)4,5- dihydro-8-methylimidazo|4,5,1-i))quinolin-6b-one, (ee) 2-I(4-(4-fluorophenyl)-piperazin-1-yl)4,5-dihydro-7-methoxyimidazoi| 4,5,1-i)quinoline-b-one, 2-(4-(4-methoxyphenyl)piperazin-1-yl)e,5-dihydroimidazoi|4,5,1-i)quinoline-b-one . in these various forms, including racemic mixtures, as well as in the form of bases or addition salts of pharmaceutically acceptable acids. 5. The method of obtaining the compound of the formula (I) according to any of claims 1-4, which differs in that the derivative of the formula LI) ; (1) GF! ІІ ю в де я сн, 60 а ч вкг КИ, К2, К2 ии п are identical to those defined in claim 1, and A is a leaving group, introduced into the reaction in the presence of an amine of the formula (II): b5 - ; (II t ШН зашк What x y 4 (zt y y where X, KZ, K4 and t are identical to those defined in claim 1, in a solvent that can be alcohol, ether or hydrocarbon, with the preparation of the compound of formula (I) according to claim 1 , and the reaction can be carried out in the presence of a base, alkali metal halides or palladium or nickel catalysts. 6. Compounds of formula (I) according to claim 5, which can be used as synthetic intermediates. 70 7. A medical product, which is characterized by the fact that it contains a compound of formula (I) according to any of claims 1-4. 8. A pharmaceutical composition, which is characterized in that it contains a compound of formula (I) according to any one of claims 1-4 and one or more pharmaceutically acceptable excipients. 9. The compound of formula (I) according to any one of claims 1-4, which is characterized by the fact that it is used for the preparation of a medical product suitable for the prevention or treatment of disorders associated with the enzyme poly(AOR-ribose) polymerase. 10. The compound of formula (I) according to any of claims 1-4, which is characterized by the fact that it is used for the preparation of a medical product intended for the prevention or treatment of myocardial infarction, cardiac ischemia, heart failure, atherosclerosis, restenosis after RTS or surgery shunting, cerebral ischemia and cerebral infarction caused by ischemia, trauma or thromboembolism, such neurodegenerative diseases as Parkinson's disease, Alzheimer's disease and Huntington's chorea, acute renal failure, in particular, of ischemic origin or after kidney transplantation, treatment of rejection after heart transplantation, accelerated atherosclerosis, inflammatory pathologies, immunological disorders, rheumatoid diseases, diabetes and pancreatitis, septic shock, acute respiratory failure syndrome, tumors and metastases, autoimmune diseases, AIDS, hepatitis, psoriasis, vasculitis, ulcerative colitis, multiple sclerosis and myasthenia gravis. high school 11. The medical product according to claim 7, which is characterized in that it is used for the treatment or prevention of disorders associated with the enzyme poly(AOR-ribose) polymerase, which contains a compound of formula (o) (I), in which CT, K2 , K2, KZ eH, X - C, p - t - 1 and KA - 4-imidazolyl or 5-methyl-4-imidazolyl group. Official bulletin "Industrial Property". Book 1 "Inventions, useful models, topographies of integrated circuit microcircuits", 2005, M 4, 15.04.2005. State Department of Intellectual Property of the Ministry of Education and Science of Ukraine. -- (ee) s - - and? -i ime) (ee) - 70 syu» ime) 60 b5