Oxocyclohexa compounds of urea, pharmaceutical composition, method of treatment


The invention relates to 4-oxocyclohexyl the urea compounds of General formula (I), where X, Y, R, R1, R2, R3, R4, R5And L, such as defined in the claims. Also described pharmaceutical composition on the basis of these compounds and a method of treating arrhythmia and cardiac fibrillation. The technical result obtained new compounds possess valuable biological properties. The invention can be used in medicine as a therapeutic agent for the treatment of arrhythmias and cardiac fibrillation. 3 S. and 11 C.p. f-crystals, 1 PL.

Description text in facsimile form (see graphic part)and


1. Oxocyclohexa connection urea of General formula

in which X represents a saturated or unsaturated 5-, 6 - or 7-membered, carbocycle;

R is chosen from the group consisting of a covalent bond, oxygen atom, carbonyl group, preferably a covalent bond; or R is absent;

Y is substituted or unsubstituted, saturated or unsaturated 5 - or 6-membered, preferably 5-membered, gay condensed ring systems; and when R represents a covalent bond, X and Y represent a ring system, connected through a covalent bond; and when Y is absent, R is covalent bond and X is connected to L through R;

R1, R2and R3independently selected from the group consisting of chlorine, fluorine, bromine, HE, and alkyl groups, or any of R1, R2and R3no, preferably chlorine, fluorine, bromine, CH3and HE;

L is chosen from the group consisting of alkylamino, alkylamino, where the nitrogen atom of the group linked to the nitrogen atom, which is 1 position 4-oxocyclohexa ring parts urea;

R4selected from the group consisting of alkyl and alkenylphenol groups;

A represents a substituted saturated straight chain or branched (C1-C8)heteroalkyl group, or a substituted or unsubstituted, saturated 5 - or 6-membered heterocycle, preferably a 6-membered heterocycle, and most preferably a heterocycle containing two nitrogen atom; and

R5represents unsubstituted (C1) or (C2) alkyl group, preferably (C1) alkyl group,

or their pharmaceutically acceptable salts or esters.

2. Oxocyclohexa connected which allows carbonyl group.

4. Oxocyclohexa connection urea under item 1, where R is missing.

5. Oxocyclohexa connection urea under item 1, where a represents C1-C8heteroalkyl group.

6. Connection on p. 1, where R is a covalent bond and is attached to X in position 1 of the groups X and Y in position 5 of group Y.

7. Connection on p. 1, where Y represents a 5-membered heterocycle, preferably oxygen-containing heterocycle, where Y is linked to the carbon end of the L in position 2 group Y.

8. The compound according to any one of paragraphs.1-7, where the heteroatom Y is oxygen, which is 1 position specified heterocycle.

9. The compound according to any one of paragraphs.1-8, where one of R1, R2or R3represents chlorine, fluorine or bromine, and two of R1, R2or R3no.

10. The compound according to any one of paragraphs.1-9, selected from the group including

1-[[(5-chloro-2-hydroxyphenyl)methylene]amino]-3-[2-(1-piperidinyl)ethyl]-2,4-imidazolidinedione hydrochloride;

3-[[(5-chloro-2-hydroxyphenyl)methylene]amino]-3-[3-(4-methylpiperidino)propyl]-2,4-imidazolidinedione hydrochloride;

3-[3-(dimethylamino)propyl]-1-[[(2-hydroxy-1-naphthalenyl)methylene]amino]-2,4-imidazolidinedione hydrochloride;

3-[3-(dimethylamino)propyl]-1-[[(2-kenolio]-2,4-imidazolidinedione hydrochloride:

1-[[[5-(4-bromophenyl)2-oxazolyl]methylene]amino]-3-[3-(dimethylamino)propyl]-2,4-imidazolidinedione hydrochloride;

1-[[(2,4-dichlorophenyl)methylene]amino]-3-[3-(4-methyl-1-piperazinil)propyl]-2,4-imidazolidinedione dhirajlal;

1-[[[5-(cyclohex-1-enyl)-2-furanyl]methylene]amino]-3-(3-dimethylaminopropyl)-2,4-imidazolidinedione hydrochloride;

3-(3-dimethylaminopropyl)-1-[[(2-fluorenyl)methylene]amino]-2,4-imidazolidinedione hydrochloride;


1-[[[5-(1-cyclohexen-1-yl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperazinil)butyl]-2,4-imidazolidinedione the dihydrochloride;

3-[2-(dimethylamino)ethyl]-1-[[(2-naphthalene)methylene]amino]-2,4-imidazolidinedione hydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-[2-(dimethylamino)ethyl]-2,4-imidazolidinedione hydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-[3-(N,N-dimethylamino)propyl]-2,4-imidazolidinedione hydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-(4-dimethylaminomethyl)-2,4-imidazolidinedione hydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-[2-(4-methyl-1-piperazinil)ethyl]-2,4-imidazolidinedione the dihydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-[2-(1-piperidinyl)ethyl]-2,4-imidazolidinedione what she dihydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-[6-(4-methyl-1-piperazinil)hexyl]-2,4-imidazolidinedione the dihydrochloride;

1-[[[3-(4-chlorophenoxy)phenyl]methylene]amino]-3-[3-(4-methylpiperazine)propyl]-2,4-imidazolidinedione the dihydrochloride;

1-[[(3-benzoyl-2,4-dichlorophenyl)methylene]amino]-3-[3-(dimethylamino)propyl]-2,4-imidazolidinedione hydrochloride;

1-[[(3-benzoyl-2,4-dichlorophenyl)methylene]amino-3-[3-[(4-methylpiperazine)propyl]-2,4-imidazolidinedione the dihydrochloride;

1-[[[5-(4-chlorophenyl)-2-furanyl]methyl]amino]-3-[4-(4-methyl-1-piperazinil)butyl]-2,4-imidazolidinedione the dihydrochloride;

3-(3-dimethylaminopropyl)-1-[[[5-(4-methylpropyl)-2-furanyl]methylene]amino]-2,4-imidazolidinedione hydrochloride;

3-[3-(dimethylaminopropyl)-1-[[[5-(4-nitrophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidinedione hydrochloride;

3-(3-(dimethylamino)propyl)-1-[[(5-phenylphenyl)methylene]amino]-2,4-imidazolidinedione hydrochloride;

3-[3-[bis-(1-methylethyl)amino]propyl]-1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-2,4-imidazolidinedione hydrochloride;

1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[3-[4-(2-methylethyl)-1-piperazinil]propyl]-2,4-imidazolidinedione the dihydrochloride;

1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(N-methyl-N-phenylethylamine)butyl]-2,4-imidazolidinedione hydrochloride;


(E,e)-1-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-3-[4-(4-methyl-1-piperazinil)-2-butene]-2, 4-imidazolidinedione the dihydrochloride;

1,1-dimethylethylene ether (L)-N-[1-[4-[[[5-(4-chlorophenyl)-2-furanyl]methylene]amino]-2,4-dioxo-3-imidazolidinyl]butyl]Proline.

11. The compound according to any one of paragraphs.1-9, where the nitrogen atom And that is not associated with the R4is substituted, and the substituents selected from the group consisting of methyl, hydroxyethylene, alkyl, aryl, heterocyclic, arylalkyl, mercaptoethanol and methanesulfonyl groups.

12. Pharmaceutical composition for the treatment of arrhythmia and fibrillation, characterized in that it includes a safe and effective amount of from 15 to 90% oxocyclohexa connection urea under item 1 or a mixture of such compounds and from 10 to 85% of pharmaceutically acceptable excipients selected from the group consisting of 0-2% corrigentov, 0-50% co-solvents, 0-5% buffer, 0-2% of surface-active agents, 0-2% preservatives; 0-5% sweeteners agents, 0-5% thickeners, 0-75% fillers, 0.5 to 2% of a lubricating agent, 1-5% of glidants, 4-15% baking powder and 1-10% of binders.

13. The pharmaceutical composition according to p. 12, wherein the pharmaceutically acceptable excipients are selected from the group consisting of the lei, co-solvents, buffer systems, surfactants, preservatives, sweetening agents, corrigentov, pharmaceutical dyes or pigments and substances substances.

14. The method of treatment of a human or other mammal suffering from cardiac arrhythmia and/or cardiac fibrillation, characterized in that it includes the introduction of the aforementioned person or other mammal a safe and effective amount of a compound according to any one of paragraphs.1-11 or pharmaceutical compositions by p. 12.


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The invention relates to 4-hydroxy-3-chinainternational and hydrazides of General formula (I), where a represents a-CH2- or-NH-, a R1, R2, R3and R4such as defined in the claims

The invention relates to new optically active proizvodnim of benzopyran formula

< / BR>
where R and R are independently selected from the group consisting of hydroxyl and a moiety that can be converted in vivo in hydroxyl, such as acyloxy, -OR4, -OC(O)R7or-OC(O)OR4(where R4represents alkyl, alkenyl, quinil or aryl; and R7represents amino, alkylamino, aminoalkyl and alkylsulfonyl); and R3represents-CH2- or-CH2CH2-; or its pharmaceutically acceptable salt, where the specified compound or salt is optically active because they contain more than 50% (by weight relative to all stereoisomers) 2S stereoisomers

The invention relates to compounds of formula (I)

< / BR>
in which Ar1denotes a heterocyclic group, which represents a pyrazole which may be substituted by one or more radicals R1, R2or R3; Ar2denotes phenyl, naphthyl or tetrahydronaphthyl, each of which optionally is substituted by one to three groups R2; L denotes a saturated or unsaturated, branched or unbranched carbon C1-C10chain; in which one or more methylene groups are optionally independently replaced by O, NH or S, and in which the linking group is optionally substituted by 0-2 of doxography; Q has a value selected from a range of: a) phenyl, naphthyl, pyridine, imidazole, Piran, etc. b) tetrahydropyran, morpholine, thiomorpholine, thiomorpholine and t

The invention relates to amide derivative of the formula I

< / BR>
where R3represents (1-6C)alkyl or halogen; m is 0, 1, 2 or 3; R1represents hydroxy, halogen, trifluoromethyl, nitro, amino, (1-6C)alkyl, (2-6C)alkenyl, (2-6C)quinil, (1-6C)alkoxy, (1-6C)alkylamino, di-[(1-6C)alkyl] amino, amino-(2-6C)alkylamino, (1-6C)alkylamino-(2-6C)alkylamino etc

The invention relates to derivatives of cyclic amines and their use as pharmaceuticals, particularly to a compound represented by the General formula (I), its pharmaceutically acceptable acid additive salts or its pharmaceutically acceptable C1-C6alcaldicios salt, R1-phenyl, C3-8-cycloalkyl, aromatic heterocycle with 1-3 heteroatoms selected from O, S, N, or combinations thereof, and these groups may be condensed with benzene ring or an aromatic heterocyclic group with heteroatoms, selected from O, S or N, or combinations thereof, and may also have different substituents

The invention relates to new salts of pyridinium General formula (I) or their pharmaceutically acceptable salts, where R1is-R4- R5or-N(R7)N(R7R9, R4choose from the group of-N(R7R6O-, N(R7R6N(R7), -OR6O-,

-OR SIG6N(R7)-, where R6- alkyl, R5choose from the group of alkyl, aryl, including heteroaryl, -COR7, -SO2R7and-COR10where R7Is H, alkyl or aryl, including heteroaryl, R2Is F, Cl, Br, J, alkyl, aryl, including heteroaryl, formyl, acyl, C(O)NR7R10or C(O)or SIG7, m = 0, 1, or 2, R3selected from the group comprising R7OR7N(R7)(R10) and CH(R7)C(O)R8, R8is R7OR7and NR7R10, R9is hydrogen, alkyl, aryl, including heteroaryl, -C(O)R10, -SO2R10, -C(S)OTHER10, -C(NH)NH(R10), -C(O)OTHER10, R10- H, alkyl, or aryl, including heteroaryl, and in each case, it is not necessarily different from R7X represents an ion halogen provided that 1) when two alkyl groups are the same carbon or nitrogen, they are not necessarily linked together with the formation of a cyclic structure, and (2) nitrogen heteroaryl ring R1

The invention relates to new N-phenylamine and N-pyridylamine derivative of the formula I

< / BR>
in which X denotes O or S;

R1and R2which may be identical or different, denote hydrogen, (C1-C6)alkyl or (C3-C8)cycloalkyl or R1and R2together with the carbon atom to which they are attached, form a (C3-C8)cycloalkyl;

R3means (C6-C12)aryl, optionally substituted by one or more radicals Y, which may be the same or different;

Y represents halogen;

R4and R5represent hydrogen;

Ar denotes one of the following groups or WITH:

< / BR>
T represents hydrogen or (C1-C6)alkyl;

T3and T4which may be identical or different, denote (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)allylthiourea;

R6and R7each denotes hydrogen or R6and R7together represent a bond;

Z denotes either (I) the divalent group-CHR9- in which the R11-, in which R10and R11together they form a bond that Z represents the group-CH=CH-, or R10and R11that may be the same or different, have the meanings indicated above for R9or (III) a divalent group-CHR12-CHR13-CH2-, in which R12and R13together they form a bond, Z represents-CH=CH-CH2-, or R12and R13that may be the same or different, have the meanings indicated above for R9,

as well as their additive salts with pharmaceutically acceptable acids or bases, and method of production thereof, pharmaceutical compositions and drug manifesting gipolipedimecescoe and antiatherosclerotic action based on them

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