Heterocyclic compounds as ccr2b antagonists

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of general formula (I) or to their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity, and to a based pharmaceutical composition. (I) where P represents phenyl optionally substituted by 1 or 2 substitutes independently selected from halogen, C1-4alkyl, cyano, trifluoromethyl, C1-4alkoxy and trifluormethylthio, and R2 has the values specified in the patent claim.

EFFECT: preparation of new compounds of general formula (I) or their pharmaceutically acceptable salts exhibiting CCR2B antagonist activity.

16 cl, 340 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)
,
where R2selected from hydrogen, groups C1-6alkyl, C3-7cycloalkyl,2-6alkenyl, C2-6quinil,3-7cycloalkyl-C1-6alkyl, non-aromatic monocyclic ring system containing 6 ring atoms, one of which represents oxygen or sulfur; heterocyclyl-C1-6alkyl, where heterocyclyl represents a non-aromatic ring system containing 5 or 6 atoms, one of which represents oxygen, aromatic monocyclic ring system containing 6 atoms, two of which are nitrogen, or a bicyclic ring system containing 9 atoms, two of which are nitrogen; heterocyclyl-C3-7cycloalkyl where heterocyclyl represents an aromatic monocyclic ring system containing 6 atoms, one of which is a nitrogen, phenyl-C1-6alkyl,
and where group C1-6alkyl, C3-7cycloalkyl,2-6alkenyl and heterocyclic-C1-6alkyl in the heterocyclic ring, possibly substituted C1-6by alkyl, hydroxy, trifluoromethyl; and
R represents phenyl, possibly substituted by 1 or 2 substituents, independently selected from halogen, C1-4of alkyl, cyano, trifloromethyl, 1-4alkoxy, triptoreline; or its pharmaceutically acceptable salt.

2. The compound according to claim 1 or its pharmaceutically acceptable salt, where R2represents a C1-4alkyl.

3. The compound according to claim 2 or its pharmaceutically acceptable salt, where R is a phenyl, substituted by 1 or 2 substituents, independently selected from halogen, C1-4of alkyl, cyano, trifloromethyl,1-4alkoxy, triptoreline.

4. The compound according to claim 1 or its pharmaceutically acceptable salt, where R is a phenyl, substituted by 1 or 2 substituents, independently selected from halogen, C1-4of alkyl, cyano, trifloromethyl,1-4alkoxy, triptoreline.

5. The compound according to claim 4 or pharmaceutically acceptable salt, where R is a phenyl, substituted by 1 or 2 substituents, independently selected from halogen.

6. The compound according to claim 5 or its pharmaceutically acceptable salt, where the specified independently halogen selected from chlorine and fluorine.

7. The compound according to claim 1 or its pharmaceutically acceptable salt, where R2represents a C1-4alkyl, and R represents phenyl, substituted with 1 or 2 Halogens.

8. The connection according to claim 7 or its pharmaceutically acceptable salt, where the specified independently halogen selected from chlorine and fluorine.

9. The compound according to claim 1 or its pharmaceutically acceptable with the l, where R is a phenyl substituted with 2 substituents independently selected from halogen, C1-4of alkyl, cyano, trifloromethyl,1-4alkoxy, triptoreline.

10. The connection according to claim 9 or its pharmaceutically acceptable salt, where R is a phenyl substituted with 2 substituents independently selected from halogen.

11. The compound according to claim 1 or its pharmaceutically acceptable salt, where the specified independently halogen selected from chlorine and fluorine.

12. The compound according to claim 1 or its pharmaceutically acceptable salt, where R2represents a C1-4alkyl, and R represents phenyl, substituted 2 Halogens.

13. The connection section 12 or its pharmaceutically acceptable salt, where these Halogens independently selected from chlorine and fluorine.

14. The compound according to claim 1, chosen from:
N-(4-chlorophenyl)-4-{[(2R)-4-ethylpiperazin-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3-chlorophenyl)-4-{[(2R)-4-ethylpiperazin-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-ethylpiperazin-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-[(2R)(4-cyclopropylmethyl-2-yl)carbonyl]-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(2-phenylethyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-methylpiperid the Zin-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3-chlorophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}-N-[4-(trifluoromethyl)phenyl]piperazine-1-carboxamide;
N-[4-chloro-3-(trifluoromethyl)phenyl]-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}-N-[3-(trifluoromethyl)phenyl]piperazine-1-carboxamide;
N-(4-chlorophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3-chloro-4-forfinal)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyliron-1-carboxamide;
N-(3,4-differenl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3-fluoro-4-were)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-second-butylpiperazine-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(tetrahydro-2H-Piran-4-yl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(4-chloro-3-forfinal)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3-chloro-4-were)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-[3-chloro-4-(trifluoromethyl)phenyl]-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(4-chloro-3-were)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(4-chloro-3-forfinal)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}p is perazin-1-carboxamide;
4-{[(2R)-4-(cyclopropylmethyl)piperazine-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(3-hydroxy-1,3-dimethylbutyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(1-methylbutyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(tetrahydrofuran-3-ylmethyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(4,4,4-trifloromethyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-({(2R)-4-[3-(5-ftorpirimidinu-2-yl)propyl]piperazine-2-yl}carbonyl)piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(tetrahydro-2H-Piran-4-ylmethyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-cyclobutylmethyl-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
4-{[(2R)-4-cyclopentylpropionyl-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
4-{[(2R)-4-cyclohexylpiperazine-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-[(2R)-piperazine-2-ylcarbonyl]piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(4-hydroxy-4-pyridine-2-illlogical)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(tetrahydro-2H-thiopyran-4-yl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-(1-cyclopropylethyl)piperazine-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-ka is oxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(1H-indazol-3-ylmethyl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-cyclobutylmethyl-2-yl]carbonyl}-N-[4-(trifluoromethyl)phenyl]piperazine-1-carboxamide;
N-(5-chloro-2-methoxyphenyl)-4-{[(2R)-4-cyclobutylmethyl-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,5-dichlorophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-[3-fluoro-5-(trifluoromethyl)phenyl]-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-[4-cyano-3-(trifluoromethyl)phenyl]-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(prop-2-EN-1-yl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(2-methylprop-2-EN-1-yl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(prop-2-in-1-yl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-[(4-tert-butylpiperazine-2-yl)carbonyl]-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
N-(3-cyanophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-[3,5-bis(trifluoromethyl)phenyl]-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(3-chloro-4-methoxyphenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(4-cyanophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
N-(4-bromophenyl)-4-{[(2R)-4-isopropylpiperazine-2-yl]rbony}piperazine-1-carboxamide;
N-[4-fluoro-3-(trifluoromethyl)phenyl]-4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}piperazine-1-carboxamide;
4-{[(2R)-4-isopropylpiperazine-2-yl]carbonyl}-N-{4-[(trifluoromethyl)thio]phenyl}piperazine-1-carboxamide;
4-{[(2R)-4-tert-butylpiperazine-2-yl]carbonyl}-N-(3,4-dichlorophenyl)piperazine-1-carboxamide;
4-{[(2R)-4-(prop-1-yl)piperazine-2-yl]carbonyl}-N-(4-trifluoromethyl-phenyl)piperazine-1-carboxamide;
4-{[(2R)-4-(prop-2-yl-1-yl)piperazine-2-yl]carbonyl}-N-{4-triptoreline)piperazine-1-carboxamide and
N-(3,4-dichlorophenyl)-4-{[(2R)-4-(prop-1-yl)piperazine-2-yl]carbonyl}piperazine-1-carboxamide,
or its pharmaceutically acceptable salt.

15. The compound or its pharmaceutically acceptable salt according to any one of claims 1 to 13, with CCR2B antagonistic activity.

16. Pharmaceutical composition having CCR2B antagonistic activity, containing the compound or its pharmaceutically acceptable salt according to any one of claims 1 to 13 and a pharmaceutically acceptable diluent or carrier.



 

Same patents:

FIELD: medicine.

SUBSTANCE: there is described application of 1-hetaryl-2-nitro-2-(3-phenyl-1,2,4-oxadiazole-5-yl)ethanes of general formula I a-m 1a, e, and R1=NO2, R2=H; 1b, f, to R1=NO2, R2=Me; 1c, g, l R1=CO2Et, R2=H; 1d, h, m R1 =CO2Et, R2 =Me; 1a-d R2 =piperidino; 1e-h R3 =1-pyrrolidinyl, 1j-m R3=morpholino as psychotropic substances.

EFFECT: substances are low-toxic and have an evident psychotropic effect on rats.

4 tbl, 4 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds which are methyl-3-azabicyclo[3.3.0]octane-7-carboxylate, N-methyl-3-azabicyclo[3.3.1]nonane-7-carboxamide, N-propyl-3-azabicyclo[3.3.1]nonane-7-carboxamide, or pharmaceutically acceptable salts thereof. The invention also relates to compounds selected from a group, a pharmaceutical composition, methods of treating or preventing central nervous system disorders, as well as use of compounds in any of claims 1-4.

EFFECT: obtaining novel biologically active compounds having activity on neural nicotinic acetylcholine receptor.

11 cl, 14 ex, 7 tbl, 2 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to a method for synthesis of hetaryl derivatives of 2-nitro-2-(3-phenyl-1,2,4-oxadiazol-5-yl)-ethanes of general formula where, I a,d,i R1=NO2, R2=H; I b,e,k R1=NO2, R2=Me; I v,g,l R1=CO2Et, R2=H; I e,z,m R1=CO2Et, R2=Me; I a-r R3=piperidinyl; I d-z R3=1-pyrrolidinyl, I i-m R3=morpholinyl, based on a nucleophilic substitution reaction of terminal chlorine in 2-nitro-1-chloro-2-(3-phenyl-1,2,4-oxadiazol-5-yl)ethanes of formula IV with 2,5 times excess piperdine, pyrrolidine or morpholine, while heating and stirring in dried ethanol and holding at temperature 25°C for 2 days.

EFFECT: efficient method of producing hetaryl derivatives.

1 cl, 2 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the 2,9-disubstituted imidazo[1,2-a]benzimidazole family, specifically to water-soluble salts of 9-aminoethyl-substituted 2-(4-fluorophenyl)imidazo[1,2-a]benzimidazole of general formula I:

,

where NR2 = pyrrolidine-, piperidine-, morpholine-; Y=HBr, H2SO4, (CH2COOH)2 and [CH(OH)COOH]2; n=1, 2.

EFFECT: novel compounds have analgesic action.

2 cl, 2 tbl, 15 ex

FIELD: chemistry.

SUBSTANCE: disclosed compounds can be used as a medicinal agent which modulates PPARδ (peroxisome proliferator-activated receptor δ). In formula I

, p is equal to 1; L2 is selected from a group which includes -XOX- and -XSX-, where X is independently selected from a group which includes a bond and C1-C4alkylene; R13 is selected from a group which includes halogen, C1-C6alkyl; R14 is selected from a group which includes -XOXC(O)OR17 and -XC(O)OR17, where X denotes a bond or C1-C4alkylene and R17 denotes hydrogen; R15 and R16 are independently selected from a group which includes -R18 and -YR18, where Y is selected from a group which includes C2-C6alkenylene, and R18 is selected from a group which includes C6-C10aryl, pyridinyl, pyrimidinyl, quinolinyl, benzo[b]furanyl, benzoxazolyl, 1,5-benzodioxanyl, 1,4-benzodioxanyl and 3,4-dihydro-2H-benzo[b][1,4]dioxepin; where any of phenyl, pyridinyl, pyrimidinyl, benzoxazolyl in R18 is independently substituted with 1-2 radicals, independently selected from a group which includes halogen, C1-C6alkyl, C2-C7alkenyl, C1-C6alkoxy group, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxy group, C3-C12cycloalkyl, phenyl, morpholinyl, pyrrolidinyl, piperidinyl, -XNR17R17, -XC(O)NR17R17, -XC(O)R19 and -XOXR19, where X denotes a bond or C1-C4alkylene; R17 is selected from a group which includes C1-C6alkyl, and R19 is selected from a group which includes C3-C12cycloalkyl, piperidinyl and phenyl. The invention also relates to use of the disclosed compounds to prepare a medicinal agent which modulates PPARδ activity, a pharmaceutical composition having PPARδ activity modulating properties, which contains a therapeutically effective amount of the disclosed compound and to use of the pharmaceutical composition in preparing a medicinal agent which modulates PPARδ activity.

EFFECT: improved properties of compounds.

10 cl, 1 tbl, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (I): , optical isomers of said compounds, as well as salts thereof having peroxisome proliferator-activated receptor subtype y (PPARy) modulating property. Values of R1, R2, X, Ar1 and Ar2 are given in the formula of invention.

EFFECT: preparation of compositions based on said compounds, as well as use of said compounds in cosmetic and pharmaceutical industry.

11 cl, 30 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted tetracyclic derivatives of tetrahydropyran, pyrrolidine and tetrahydrothiophene of general formula (I), their pharmaceutically acceptable addition salts, their stereochemically isomeric forms, their N-oxide forms, in which all substitutes are defined in claim 1 of the formula of invention. These compounds have binding affinity to serotonin receptors, particularly 5-HT2A and 5-HT2C receptors, and to dopamine receptors particularly D2 dopamine receptors, and have norepiniphrine reuptake inhibition properties. The invention also relates to a pharmaceutical composition containing said compounds, method of preparing said composition and use of said compounds as medicinal agents, particularly for preventing and/or treating several psychiatric and neurological disorders.

EFFECT: new compounds have useful biological properties.

12 cl, 3 tbl, 49 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of the formula (I) where: A is an aryl or a 5-member heteroaryl containing a S heteroatom, possibly substituted with one or two substitutes selected from a group consisting of halogen, C1-6-alkyl or C1-6-alkoxy; n equals 1 or 2; p equals 1, 2, 3 or 4; q equals 1; r equals 0 or 1; R1 is C2-6-alkynyl substituted with aryl, or C1-6-alkyl possibly substituted with one-five substitutes selected from a group consisting of halogen, hydroxy, C1-6-alkyl, C1-6-halogenoalkyl, -OC(O)-C1-6-alkyl, C3-10-cycloalkyl, C1-6-alkoxy, possibly substituted with one, two or three halogens or aryl, aryl which is possibly substituted with a halogen or C1-6-alkoxy, 5-9-member heteroaryl, one, two or three ring atoms of which are heteroatoms selected from N or O, and the rest of the ring atoms are C atoms, possibly substituted with C1-6-alkyl, and phenoxyl, or is C1-6-alkoxy, or is C3-10-cycloalkyl which is possibly substituted with one or more Ra, or is a 5- or 6-member heterocycloalkyl containing one, two or three heteroatoms selected from nitrogen, oxygen or sulphur, possibly substituted with one or more Ra, or is an aryl possibly substituted with one or more Ra, or is a 5-10-member heteraryl, one, two or three ring atoms of which are heteroatoms selected from N, O and S, and the rest of the ring atoms are C atoms, possibly substituted with one or more Ra, or is -NRbRc, where Rb is H or C1-6-alkyl and where Rc is H, C1-6-alkyl or aryl, possibly substituted with one or more Ra, where Ra is selected from: halogen, cyano, oxo, hydroxy, halogenobenzenesulfonyl, C1-6-alkyl, possibly substituted with one, two or three substitutes selected from a group consisting of 5-10-member heterocycloalkyl and aryl, which is possibly substituted with halogen or C1-6-alkoxy, C1-6-halogenoalkyl, C1-6-halogenoalkoxy, C1-6-alkoxy, possibly substituted with aryl or 5-10-member heteroaryl, one, two or three ring atoms of which are heteroatoms selected from N, O and S, and the rest of the ring atoms are C atoms, which is possibly substituted with C1-6-alkyl, aryloxy, -NH(CO)-C1-6-alkyl, -O(CO)-C1-6-alkyl, C1-6-alkylsulfonyl, aryl, 4-6-member heterocycloalkyl containing one, two or three heteroatoms selected from nitrogen, oxygen or sulphur, possibly substituted with hydroxy, C1-6-alkyl or oxo, 5-10-member heteroaryl,one, two or three ring atoms of which are heteroatoms selected from N and O, and the rest of the ring atoms are C atoms, possibly substituted with C1-6-alkyl or oxo, and di(C1-6)alkylamino; R2 is H, OH, C1-6-alkyl or halogen; as well as their pharmaceutically acceptable salts. The invention also relates to medicine and to use of the compounds in any of paragraphs 1-24.

EFFECT: obtaining novel biologically active compounds with affinity to dopamine D3 receptor and to serotonin 5- HT2a receptor.

27 cl, 86 ex

FIELD: chemistry.

SUBSTANCE: invention claims compound of the formula I, where R1 is alkyl; phenylalkyl optionally substituted by halogen; phenyl optionally substituted by halogen, halogen alkyl or alkoxy; thienyl optionally substituted by halogen; or benzo[b]thienyl optionally substituted by halogen; R2 is pyridyl or pyrimidinyl; R3 is alkyl; halogen alkyl; phenyloxylalkyl optionally substituted by halogen or alkyl; phenyl optionally substituted by halogen, alkyl or alkoxy; thienyl or alkylsilyl; R4 is H; or its salt, and methods of obtainment thereof. Additionally invention claims intermediate compound of the formula VI and method of its obtainment, composition for control of pathogenic microbes, and various methods of pathogenic microbe control.

EFFECT: improved efficiency of application.

29 cl, 1 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I, which are HSP90 (heat-shock proteins) inhibitors and can be used to prepare a medicinal agent for treating tumorous diseases affected by HSP90 inhibition. In formula I R1 denotes Hal, H, OA or A, R2, R3 each independently denotes -O-(X)s-Q, -NHCO-(X)s-Q, -CONH-(X)s-Q, -NH(CO)NH-(X)s-Q, -NH(CO)O-(X)s-Q, -NHSOr(X)s-Q, NHCOA, Hal, Het or H, where, if R2=H, then R3≠H, or if R3=H, then R2≠H, R4 denotes H, R5 denotes H, Hal, A, OA, (CH2)nCOOH, (CH2)nCOOA, O(CH2)oCONH2, NHCOOA, NHCO(CH2)nNH2, NHCONHA or O(CH2)oHet1, A denotes a straight or branched alkyl containing 1-10 carbon atoms, in which 1-5 hydrogen atoms may be substituted with F, Cl and/or Br, X denotes a straight or branched C1-C10 alkylene which is unsubstituted or substituted once, twice or thrice by A, O A, OH, Hal, CN, COOH, COOA, CONH2, NH2, NHCOA, NHCOOA, Q denotes H, Ar or Het, Ar denotes phenyl which is unsubstituted or substituted once, twice or thrice with A, OA, OH, NO2, Hal, CN, (CH2)nCOOH, (CH2)nCOOA and/or tetrazole, Het denotes a cyclic saturated or aromatic 5-6-member heterocycle containing 1-2 N and/or O atoms, optionally condensed with a benzene ring which may be substituted once, twice or thrice with A, OA, OH and/or =O (carbonyl oxygen), Het1 denotes a monocyclic saturated, unsaturated or aromatic heterocycle containing 1-2 N and/or O atoms, which may be mono- or disubstituted with A, OA, OH, Hal and/or =O (carbonyl oxygen), Hal denotes F, Cl, Br or I, n equals , 1, 2, 3 or 4, o equals 1, 2 or 3, s equals 0, 1 or 2.

EFFECT: high efficiency of using said derivatives.

4 cl, 4 dwg, 1 tbl, 29 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: present invention presents new compounds which are modulators of cannabinoid receptors, particularly modulators of cannabinoid receptors 1 (CB1) or cannabinoid receptors 2 (CB2), and an application thereof for treating diseases, conditions and/or disorders regulated by a cannabinoid receptor (such as painful sensations, neurodegenerative disorders, ingestion disorders, weight loss or weight control and obesity), as well as based pharmaceutical compositions. New compounds are characterised by graphic formulas

in which radicals and groups have the values specified in the patent claim.

EFFECT: higher efficiency of applying the composition.

55 cl, 13 tbl, 3 dwg, 802 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: there is described new macrocyclic compound of general formula 1-c:

and its pharmaceutically acceptable acid or base addition salts or its stereoisomers (the radical values are presented in the patent claim).

EFFECT: producing the compounds which are hepatitis type C virus inhibitors and can find application in medicine.

9 cl, 1 tbl, 95 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula

where there are R3/R3', R4/R4' and R5/R5' where at least one of either R4/R4' or R5/R5' always represents a fluorine atom, and the other radical values are disclosed in the description.

EFFECT: making the compounds which are γ-secretase inhibitors, and can be effective in treating Alzheimer's disease or advanced cancers, including but not limited to carcinoma of uterine cervix and breast carcinoma and malignant tumours of hematopoietic system.

15 cl, 3 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to novel 3,4-substituted pyrrolidine derivatives of general formula or pharmaceutically acceptable salts thereof, where R1 is an acyl selected from values given paragraph 1 of the formula of invention; R2 is unsubstituted C1-C4-alkyl or C3-C7-cycloalkyl; R3 is a fragment selected from a group of fragments of formulae: (a), (b),

(c) and (f), where any of the fragments of formulae given above (a), (b) and (f), the star (*) indicates a bond of the corresponding fragment R3 with the molecule residue in formula I; Ra denotes N-C1-C4-alkylaminocarbonyl, N-phenylaminocarbonyl, N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl- C1-C4-alkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C1-C4-alkyl)-N-(C3-C7-cycloalkyl-C1-C4-alkyl)aminocarbonyl, N,N-di-(C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(phenyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl-C1-C4-alkyl)aminocarbonyl, N-(C3-C7-cycloalkyl)-N-(tetrahydropyranyl)aminocarbonyl or hydrogen; Rb and Rc are independently selected from a group comprising unsubstituted C1-C4-alkyl, unsubstituted monocyclic aryl, unsubstituted monocyclic heterocyclyl, unsubstituted or substituted monocyclic C3-C7-cycloalkyl, unsubstituted aryl- C1-C4-alkyl, usubstituted monocyclic C3-C7-cycloalkyl- C1-C4-alkyl, hydrogen or acyl, where the acyl is selected from values given in paragraph 1 of the formula of invention; or Rb and Rc together may form a 6-member nitrogen-containing ring which may be unsubstituted or disubstituted with =O; Rd in the fragment of formula (c) denotes a phenyl or phenyl-C1-C4-alkyl; Re denotes hydrogen or C1-C4-alkyl; and m equals 2; each of R4 and R5 denotes hydrogen; and T denotes methylene. The invention also relates to the pharmaceutical composition based on the compound of formula I and a method of treating hypertension using the compound of formula I.

EFFECT: novel pyrrolidine derivatives having renin inhibiting activity are obtained.

7 cl, 19 tbl, 37 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula

where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula

in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.

EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.

39 cl, 7 tbl, 180 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of formula I in which cycle A represents unsaturated carbocycle with double bonds, which is selected from phenyl or naphtyl; 1 can take value from 1 to 3; m can take value 0, 2 or 3; n can take value 0 or 2; R1 represents a hydrogen atom, (C1-3)alkyl group; R2 represents(C1-6)alkyl group, which is possibly substituted with substituent, selected from C6-cycloalkyl, monocyclic heteroaryl, selected from thiophene, aryl group, selected from phenyl, in form of base or salt of bonding with an acid. Invention also relates to pharmaceutical composition, based on formula I compound, to application of formula I compound for obtaining medication, to method of obtaining formula I compound and to application of formula compound for obtaining formula 1 compound.

EFFECT: obtained are novel isoquinoline and benzo[h]isoquinoline derivatives, possessing properties of antagonists of histamine type H3 receptor.

9 cl, 1 tbl, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula 2: and to its pharmaceutically acceptable salts and their mixtures, where values of R, M, Q, Z, W, D radicals are described in i.1 of the invention formula. Invention also relates to pharmaceutical compositions, which possess inhibiting activity with respect to Btk, based on formula 2 compounds.

EFFECT: obtained are novel compounds and based on them pharmaceutical compositions which can be applied in medicine for treatment of patients with diseases associated with inhibiting Btk activity and/or B-cell activity.

55 cl, 19 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted cyclic compounds with the following general formula I or II and to pharmaceutically acceptable salts thereof and to all stereo isomers and optical isomers thereof:

, , where n equals 1, X and Y are NH; R1 and R2 independently represent one substitute selected from a group consisting of aryl; 2-, 3-, or 4-pyridyl; aryl substituted with one, two or three groups selected from C1-C4alkyl, nitro, carboxyl, aldehyde, alkoxy, amino, amido, carbamide, mercapto, methylthio, ethylthio; R3 and R4 independently represent one substitute selected from a group consisting of aryl; 2-, 3- or 4-pyridyl; aryl substituted with one, two or three groups selected from C1-C4alkyl, nitro, carboxyl, aldehyde, alkoxy, amino, amido, carbamide, mercapto, methylthio, ethylthio; 2-, 3- or 4-pyridyl, substituted with one, two or three groups selected from C1-C4alkyl, nitro, carboxyl, aldehyde, alkoxy, amino, amido, carbamide, mercapto, methylthio, ethylthio. The invention also relates to a method of producing a range of substituted cyclic compounds and their salts in any of subclaims 1-4, to a pharmaceutical composition, to use, to a method of treating and preventing diseases as well as to an assembly.

EFFECT: obtaining new biologically active compounds suitable for treating or preventing diseases or symptoms, arising from or accompanied with violation of secretion and/or function of insulin.

13 cl, 4 ex, 3 tbl, 6 dwg

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