Derivatives showing ppar-receptor agonist activity

FIELD: medicine, pharmaceutics.

SUBSTANCE: compound of formula pharmaceutically acceptable salt or solvate of a compound or salt (I), ring Q represents optionally substituted monocyclic or condensed (C6-C12)aryl or optionally substituted monocyclic or condensed heteroaryl where said substitutes are chosen from: halogen; (C1-C6)alkyl optionally substituted by 1-3 halogen atoms; (C1-C6)alkylsulphonyl; phenyl optionally substituted by 1 or 2 substitutes chosen from halogen, (C1-C6)alkyl which can be substituted by 1-3 halogen atoms, groups (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl optionally substituted by halogen; or oxo; Y1 represents a bond or -NR6-CO-, where R6 represents hydrogen, ring A represents optionally substituted a nonaromatic heterocyclyldiyl where said substitutes are chosen from (C1-C6)alkyl optionally substituted by groups hydroxy, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxymethyl; thienyl; 4-8-members monocyclic nonaromatic heterocycle having 1 or 2 heteroatoms chosen from N or O, and optionally substituted by 1 or 2 substitutes chosen from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino; a group of formula: -Y2Z'- represents a group of formula: [Formula 2] each R7 independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl, each of R8 and R9 independently represents hydrogen or (C1-C6)alkyl, n is equal to an integer 0 to 3, Z1 represents a bond, -O-, -S- or-NR9 - where R9 represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulphonyl, ring B represents optionally substituted aromatic carbocyclediyl or optionally substituted aromatic heterocyclediyl where said substitutes are chosen from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo; Y3 represents a bond optionally substituted (C1-C6)alkylene or (C3-C6)cycloalylene, optionally interrupted -O- or optionally substituted (C2-C6)alkenylene where said substitutes are chosen from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl; Z2 represents COOR3; R3 represents hydrogen or (C1-C6)alkyl.

EFFECT: preparation of new compounds.

30 cl, 9 tbl, 944 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I):
[formula 1]

its pharmaceutically acceptable salt or MES,
where the ring Q represents a possibly substituted monocyclic or condensed (C6-C12)aryl or possibly substituted monocyclic or condensed heteroaryl, where these substituents selected from: halogen; (C1-C6)alkyl, possibly substituted by 1 to 3 halogen atoms; (C1-C6)alkylsulfonyl; phenyl, possibly substituted by 1 or 2 substituents selected from halogen, (C1-C6)alkyl which may be substituted by 1-3 halogen atoms, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl, possibly substituted with halogen; or oxo; provided that the ring Q represents the Oh unsubstituted 11N-dibenz[b,e]-azepin-6-Il,
Y1is a bond or-NR6-CO-, where R6represents hydrogen,
provided that Y1represents-NR6-CO-when the ring Q is an unsubstituted monocyclic (C6-C12)aryl, and ring Q is a phenyl, substituted (C1-C6)alkylhalogenide when the ring Q represents a monocyclic C6-C12)aryl, and Y1is a relationship
ring a represents a possibly substituted non-aromatic heterocyclyl, where these substituents selected from (C1-C6)alkyl, possibly substituted by hydroxy groups, (C1-C6)alkylamino, di(C1-C6)alkylamino, morpholino, (C1-C6)alkylaminocarbonyl, di(C1-C6)alkylaminocarbonyl; cyano; (C3-C6)cycloalkyl; (C1-C6)alkoxy; (C1-C6)alkoxy(C1-C6)alkyl; phenyl; benzyl; benzyloxyethyl; tanila; 4-8-membered monocyclic non-aromatic heterocycle having 1 or 2 heteroatoms selected from N or O, and possibly substituted by 1 or 2 substituents selected from (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and oxo; (C1-C6)alkylamino; di(C1-C6)alkylamino;
provided that the ring Q is connected to the nitrogen atom of ring A, when Y1is a relationship
a group of the formula-Y2Z1- is a group of the formula:
[formula 2]
,, or,
provided that the group of the formula: -Y2Z1- does not represent a-CH2-CH2-O - or-O-when the ring Q is an unsubstituted benzothiazol-2-yl or unsubstituted benzoxazol-2-Il,
each R7independently represents hydrogen, (C1-C6)alkyl or (C3-C6)cycloalkyl,
each of R8and R9independently represents hydrogen or (C1-C6)alkyl,
n is an integer from 0 to 3,
Z1represents a bond, -O-, -S - or-NR9-where R9represents hydrogen, (C1-C6)alkyl, acyl or (C1-C6)alkylsulfonyl,
the ring represents a possibly substituted aromatic carbocyclic or possibly substituted aromatic heterocyclyl, where these substituents selected from (C1-C6)alkyl, halogen, (C1-C6)alkoxy and oxo;
Y3that is the link, possibly substituted (C1-C6)alkylene or (C3-C6)cycloalkyl, possibly interrupted by-O-, or substituted (C2-C6)albaniles, where these substituents selected from (C1-C6)alkyl, (C3-C6)cycloalkyl, halogen and (C1-C6)alkoxycarbonyl;
Z2represents COOR3;
R3represents hydrogen or (C1-C6)alkyl;
where specified monocyclic heteroaryl means 4-8-membered monocyclic aromatic heterocycle containing 1 or more heteroatoms selected the C O S and N in the ring;
specified condensed heteroaryl means a group derived from a condensed aromatic heterocycle, in which the aromatic carbon ring or an aromatic heterocycle condensed with a monocyclic aromatic heterocycle derived from the above-mentioned monocyclic heteroaryl;
specified non-aromatic heterocyclyl means a bivalent group derived by removing 2 hydrogen atoms from 4 to 10-membered non-aromatic heterocycle containing 1 or more heteroatoms selected from O, S and N in the ring, where specified the non-aromatic heterocycle may be Allenby bridge;
specified aromatic carbocyclic means a bivalent group derived by removing a hydrogen atom from the above-mentioned (C6-C12)aryl; specified aromatic heterocyclyl means a bivalent group derived by removing a hydrogen atom from the above heteroaryl;
provided that the compound in which a group of the formula-Y2Z1- is a group of the formula:
[formula 4]

n is 0, and Z1represents a bond, is excluded, and excluding the following compounds:
ethyl-4-[2-[1-(2-benzothiazolyl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(2-benzoxazolyl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(4-methylthiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(4-phenylthiazol-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(2-thiazolyl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(5-methyl-1,3,4-thiadiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(1,3,4-thiadiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(4-phenyl-1,3,5-thiadiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(5-bromo-1,3,4-thiadiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(1,2-benzisothiazol-3-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-1,3,5-thiadiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[3-[4-(5-methyl-1,3,4-thiadiazole-2-yl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[2-[4-(2-benzoxazolyl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[2-[4-(5-bromo-1,3,4-thiadiazole-2-yl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[3-[4-(5-bromo-1,3,4-thiadiazole-2-yl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[3-[4-(2-benzothiazolyl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[3-[4-(1,3,4-thiadiazole-2-yl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[2-[4-(2-thiazolyl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[3-[4-(2-benzoxazolyl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[3-[4-(2-thiazolyl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[2-[4-(2-benzothiazolyl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[2-[4-(1,2-benzoxazol-3-yl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[3-[4-(1,2-benzoxazol-3-yl)-1-piperazinil]propoxy]benzoate;
ethyl-4-[2-[1-(5-what enyl-1,3,4-thiadiazole-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[4-(4-phenyl-1,3-thiazol-2-yl)-1-piperazinil]ethoxy]benzoate;
ethyl-4-[2-[1-(5-methyl-1,3,4-oxadiazol-2-yl)-4-piperidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(5-bromo-1,3,4-thiadiazole-2-yl)-4-pyrrolidinyl]ethoxy]benzoate;
ethyl-4-[2-[1-(5-chloro-1,3-thiazol-2-yl)-4-piperidinyl]ethoxy]benzoate;
(4-{2-[4-phenyl-piperazine-1-yl]ethoxy}phenyl)acetic acid;
(4-{2-[4-(3-chlorophenyl)-piperazine-1-yl]ethoxy}phenyl)acetic acid;
(4-{2-[4-(3-triptoreline)-piperazine-1-yl]ethoxy}phenyl)acetic acid;
(4-{2-[4-(pyridin-2-yl)-piperazine-1-yl]ethoxy}phenyl)acetic acid;
(4-{2-[4-(pyrimidine-2-yl)-piperazine-1-yl]ethoxy}phenyl)acetic acid;
hydrochloride 4-[[4-(2-pyridyl)-1-piperazinil]methyl]phenylacetic acid;
hydrochloride 4-[[4-(2-tolyl)-1-piperazinil]methyl]phenylacetic acid;
hydrochloride 4-[(4-phenyl-1-piperazinil)methyl]phenylacetic acid;
hydrochloride 4-[[4-(2-forfinal)-1-piperazinil)methyl]phenylacetic acid;
hydrochloride 4-[[4-(2,5-dimetilfenil-1-piperazinil]methyl]phenylacetic acid;
2-[(4-phenylpiperazin-1-yl)methyl]benzimidazole-4-carboxylic acid;
2-[[4-(meta-(trifluoromethyl)phenyl)piperazine-1-yl]methyl]benzimidazole-4-carboxylic acid;
2-[[4-(meta-chlorophenyl)piperazine-1-yl]methyl]benzimidazole-4-carboxylic acid;
2-[[4-(naphthas-1-yl)piperazine-1-yl]methyl]benzimidazole-4-carboxylic acid; and
2-[[4-(2,3-dihydro-1,4-benzodioxan-5-yl]piperazine-1-yl]m is Teal]benzimidazole-4-carboxylic acid.

2. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the ring And represents a group of the formula:
[formula 5]


or

where X4represents N or CR5where R5represents hydrogen or a possibly substituted (C1-C6)alkyl,
X5represents O, S, NR16or CR17R18where each of R16-R18independently represents hydrogen, possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl, provided that the compound in which X4represents CR5and X5represents CR17R18excluded,
each R4independently represents a possibly substituted (C1-C6)alkyl, (C1-C6)alkoxy, phenyl or benzyl,
where these substituents are as defined for ring As in claim 1;
m is an integer from 0 to 2,
the relationship of X4connects with Y1the other link connects with Y2and another link to the ü can connect with X 5when X5represents NR16or CR17R18.

3. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the ring And represents a group of the formula:
[formula 6]

X4represents N or CR5where R5represents hydrogen or a possibly substituted (C1-C6)alkyl,
X5represents NR16or CR17R18where each of R16-R18independently represents hydrogen, possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl,
each R4independently represents a possibly substituted (C1-C6)alkyl, (C1-C6)alkoxy, phenyl or benzyl,
where these substituents are as defined for ring As in claim 1;
m is an integer from 0 to 2,
the relationship of X4connects with Y1the other link connects with Y2and another link can connect with X5.

4. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the ring And represents a group of the formula:
[formula 7]

each R4independently represents a possibly substituted (C1-C6)alkyl or (C1-C6)alkoxy, where these substituents ablauts is such as defined for ring As in claim 1; and
m is an integer 1 or 2.

5. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the ring And represents a group of the formula:
[formula 8]

R17represents a possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl, where these substituents are as defined for ring As in claim 1;
the relationship between N connects with Y1and the connection from connects with Y2.

6. The compound, its pharmaceutically acceptable salt or MES according to claim 5, where Q is selected from any of the following patterns:



,
where R and R' is selected from: halogen; (C1-C6)alkyl, possibly substituted by 1 to 3 halogen atoms; (C1-C6)alkylsulfonyl; phenyl, possibly substituted by 1 or 2 substituents selected from halogen, (C1-C6)alkyl which may be substituted by 1-3 halogen atoms, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy,(C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl, possibly substituted with halogen, or oxo.

7. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the ring And represents a group of the formula:
[formula 9]

X4represents N or CR5where R5represents hydrogen or a possibly substituted (C1-C6)alkyl,
X5represents NR16or CR17R18where each of R16-R18independently represents hydrogen, possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl provided that the compound in which X4is
a CR5and X5represents CR17R18excluded,
each R4independently represents a possibly substituted (C1-C6)alkyl, (C1-C6)alkoxy, phenyl or benzyl,
where these substituents are as defined for ring As in claim 1;
m is an integer from 0 to 2,
the relationship of X4connects with Y1the other link connects with Y2and another link can connect with X5.

8. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where the ring Q represents a substituted condensed the initial heteroaryl, where these substituents are as defined for ring Q item 1.

9. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where the ring Q represents a substituted benzofuran, substituted benzothieno, substituted benzopyrrole, substituted benzoxazolyl, substituted benzisoxazole, substituted benzothiazolyl, substituted benzothiazolyl, substituted benzoimidazolyl or substituted benzimidazolyl, where these substituents are as defined for ring Q item 1.

10. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where a group of the formula:
[formula 10]

represents a group of the formula:
[formula 11]

R1represents hydrogen, halogen, (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms, or a possibly substituted phenyl,
R2represents halogen, (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms, possibly substituted phenyl or possibly substituted heteroaryl, or
R1and R2can be taken together with the neighboring carbon atom and the 5-membered ring including X1and X3as a constructive atoms, with formation of a substituted condensed heteroaryl,
X1represents N or CR10and
X3the stand is made by an NR 11, O or S, where each of R10and R11independently represents hydrogen or (C1-C6)alkyl,
where these substituents are as defined for ring Q item 1.

11. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where a group of the formula:
[formula 12]

represents a group of the formula:
[formula 13]

R1represents hydrogen, halogen or (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms,
R2represents halogen, (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms, possibly substituted phenyl or possibly substituted heteroaryl, or
R1and R2can be taken together with the neighboring carbon atom and the 5-membered ring including X1and X3as a constructive atoms, with formation of a substituted condensed heteroaryl,
X1represents N or CR12and
X3represents NR13, O or S, where each of R12and R13independently represents hydrogen or (C1-C6) alkyl,
where these substituents are as defined for ring Q item 1.

12. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where a group of the formula:
[formula 14]

is the Wallpaper group of the formula:
[formula 15]

each R1independently represents hydrogen, halogen or (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms,
R2represents halogen, (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms, possibly substituted phenyl or possibly substituted heteroaryl,
X1represents N or CR19,
X3represents N or CR20where each of R19and R20independently represents hydrogen or (C1-C6)alkyl, and provided that either X1or X3represents N,
where these substituents are as defined for ring Q item 1.

13. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where a group of the formula-Y2Z1- is a group of the formula:
[formula 16]

each of R8and R9independently represents hydrogen or (C1-C6)alkyl,
n is an integer from 0 to 2, and Z1represents a bond, -O - or-S-.

14. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where the ring represents a possibly substituted phenylene, possibly substituted andolder, possibly substituted benzofuranyl, possibly substituted benzothiophenes, possibly substituted purandar or perhaps replaced offender, where these substituents are as defined for rings in claim 1.

15. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where Y3that is the link, possibly substituted (C1-C6)alkylene, possibly interrupted by-O-, or substituted (C2-C6)albaniles, where these substituents are as defined for Y3in item 1.

16. The compound, its pharmaceutically acceptable salt or MES according to claim 1 or 2, where Z2represents COOR3where R3represents hydrogen or (C1-C6)alkyl.

17. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the group of the formula:
[formula 17]

represents a group of the formula:
[formula 18]

R1represents hydrogen,
R2represents a possibly substituted phenyl, or
R1and R2can be taken together with the neighboring carbon atom and the 5-membered ring including X1and X3as a constructive atoms, with formation of a substituted condensed heteroaryl,
X1represents N or CR10where R10represents hydrogen,
X3represents O or S,
where these substituents are as defined for ring Q in claim 1;
Y1the present is the focus of a relationship,
ring And represents a group of the formula:
[formula 19]
or
X4represents N,
X5represents NR16or CR17R18where each of R16-R18independently represents hydrogen, possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl,
each R4independently represents a possibly substituted (C1-C6)alkyl, (C1-C6)alkoxy, phenyl or benzyl,
where these substituents are as defined for ring As in claim 1;
m is an integer from 0 to 2,
the relationship of X4connects with Y1the other link connects with Y2and another link can connect with X5,
a group of the formula:-Y2Z1- is a group of the formula:
[formula 20]

each of R8and R9independently represents hydrogen or (C1-C6)alkyl,
n is an integer from 0 to 2,
Z1represents a bond, -O - or-S-,
the ring represents a possibly substituted phenylene, possibly substituted purandar or possibly substituted theoffender,
where the substituent(s) mentioned phenylene, purandara or difendere rings In the selected(s) from groups who, consisting of halogen, (C1-C6)alkyl and (C1-C6)alkoxy,
Y3that is the link, possibly substituted (C1-C6)alkylene, possibly interrupted by-O-, or substituted (C2-C6)albaniles, where the substituent(s) specified (C1-C6)alkylene or (C2-C6)Alcanena in the Y3the selected(s) from the group consisting of halogen and (C1-C6)alkyl, and
Z2represents COOR3where R3represents hydrogen or (C1-C6)alkyl.

18. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where the group of the formula:
[formula 21]

represents a group of the formula:
[formula 22]

each R1independently represents hydrogen, halogen or (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms,
R2represents (C1-C6)alkyl, possibly substituted by 1-3 halogen atoms, or a possibly substituted phenyl,
X1represents N or CR19,
X3represents N or CR20where each of R19and R20independently represents hydrogen or (C1-C6)alkyl, provided that either X1or X3represents N,
where these substituents are as defined for ring Q in claim 1;
Y1is a relationship
ring And represents a group of the formula:
[formula 23]
or
X4represents N,
X5represents NR16or CR17R18where each of R16-R18independently represents hydrogen, possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl,
each R4independently represents a possibly substituted (C1-C6)alkyl, (C1-C6)alkoxy, phenyl or benzyl,
where these substituents are as defined for ring As in claim 1;
m is an integer from 0 to 2,
the relationship of X4connects with Y1the other link connects with Y2and another link can connect with X5,
a group of the formula-Y2Z1- is a group of the formula:
[formula 24]

each of R8and R9independently represents hydrogen or (C1-C6)alkyl,
n is an integer from 0 to 2,
Z1represents a bond, -O - or-S-,
the ring represents a possibly substituted phenylene, possibly substituted purandar or possibly substituted theoffender, where the substituent(s) mentioned phenylene, purandara or difendere,
ring In the selected(s) from the group consisting of halogen, (C1-C6)alkyl and (C1-C6)alkoxy,
Y3is a tie which, possibly substituted (C1-C6)alkylene, possibly interrupted by-O-, or substituted (C2-C6)albaniles, where the substituent(s) specified (C1-C6)alkylene or (C2-C6)Alcanena in the Y3the selected(s) from the group consisting of halogen and (C1-C6)alkyl, and
Z2represents COOR3where R3represents hydrogen or (C1-C6)alkyl.

19. The compound, its pharmaceutically acceptable salt or MES according to claim 1, where
Y1is a relationship
ring And represents a group of the formula:
[formula 25]

each R4independently represents a possibly substituted (C1-C6)alkyl or (C1-C6)alkoxy, where these substituents are as defined for ring As in claim 1;
m is an integer 1 or 2,
a group of the formula-Y2Z1-is a group of the formula:
[formula 26]

each of R8and R9independently represents hydrogen or (C1-C6)alkyl,
n is an integer 1 or 2,
Z1is a bond or-O-,
the ring represents a possibly substituted phenylene, where these substituents are as defined for rings in claim 1;
Y3represents a possibly substituted (C1-C6)alkylene, possibly interrupted by-O-,
where the substituent(s) specified (C1-C6)alkylene in the Y3the selected(s) and the group, consisting of halogen and (C1-C6)alkyl, and
Z2represents COOR3where R3represents hydrogen or (C1-C6)alkyl.

20. The compound, its pharmaceutically acceptable salt or MES according to claim 1,
where Y1is a relationship
ring And represents a group of the formula:
[formula 27]

R17represents a possibly substituted (C1-C6)alkyl, cyano, possibly substituted the non-aromatic heterocycle, thienyl, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, benzyl, or (C3-C6)cycloalkyl, where these substituents are as defined for ring As in claim 1;
the relationship between N connects with Y1and the connection from connects with Y2the group of the formula-Y2Z1- is a group of the formula:
[formula 28]

each of R8and R9independently represents hydrogen or (C1-C6)alkyl,
n is equal to 2,
Z1represents-O-,
the ring represents a possibly substituted phenylene, where these substituents are as defined for rings in claim 1;
Y3represents a possibly substituted (C1-C6)alkylene, possibly interrupted by-O-,
where the substituent(s) specified (C1-C6)alkylene in the Y3the selected(s) from the group consisting of halogen and (C1-C6)alkyl, and
Z2is a COR 3where R3represents hydrogen or (C1-C6)alkyl.

21. The compound, its pharmaceutically acceptable salt or MES according to claim 20, where Q is selected from any of the following patterns:



,
where R and R' is selected from: halogen; (C1-C6)alkyl, possibly substituted by 1 to 3 halogen atoms; (C1-C6)alkylsulfonyl; phenyl, possibly substituted by 1 or 2 substituents selected from halogen, (C1-C6)alkyl which may be substituted by 1-3 halogen atoms, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl, possibly substituted with halogen, or oxo.

22. Pharmaceutical composition having agonist activity of receptor-activated proliferation peroxisome (PPAR)containing the compound, its pharmaceutically acceptable salt or MES according to any one of claims 1 to 21 as an active ingredient.

23. Pharmaceutical composition for preventing and/or treating diseases associated with the receptor(s)activated(is) proliferation peroxisome, containing compound, its pharmaceutically acceptable salt or MES according to any one of claims 1 to 21 as an active ingredient.

24. The compound of the formula:
[formula 29]

its salt, or MES,
where the ring Q has the same meaning as defined in claim 1, and R4represents (C1-C6)alkyl or (C1-C6)alkoxy.

25. The compound of the formula:
[formula 30]

its salt, or MES,
where Y2, Z1, ring B, Y3and Z2have the same meanings as defined in claim 1,
each R4independently represents a (C1-C6)alkyl, and
Rxrepresents hydrogen or a protective group for amino.

26. The compound of the formula:
[formula 31]

its salt, or MES,
where the ring Q has the same meaning as defined in claim 1,
R17represents (C1-C6)alkyl, cyano, the non-aromatic heterocycle, as defined in claim 1, or (C3-C6)cycloalkyl,
each of R8and R9independently represents hydrogen,
n is an integer from 1 to 3, and
X10represents halogen or hydroxy.

27. The compound, its salt or MES on p, where Q is selected from any of the following patterns:




where R and R' is selected from: halogen; (C1-C6)alkyl, possibly substituted by 1 to 3 halogen atoms; (C1-C6)alkylsulfonyl; phenyl, possibly substituted by 1 or 2 substituents selected from halogen, (C1-C6)alkyl which may be substituted by 1-3 halogen atoms, (C1-C6)alkylamino, di(C1-C6)alkylamino, (C1-C6)alkoxy, (C1-C6)alkoxy(C1-C6)alkyl and (C1-C6)alkylthio; monocyclic or condensed heteroaryl, possibly substituted with halogen, or oxo.

28. The compound of the formula:
[formula 32]

its salt, or MES,
where each R4independently represents a (C1-C6)alkyl,
m is 1 or 2, and
Rxrepresents hydrogen or a protective group for amino.

29. The compound of the formula:
[formula 33]

its salt, or MES,
where each R4represents (C1-C6)alkyl,
each of R8and R9independently represents hydrogen,
n is an integer from 1 to 3,
Rxrepresents hydrogen or a protective group for amino, and
X10represents hydroxy or halogen.

30. The compound of the formula:
[formula 34]

it is salt or MES,
where R17represents (C1-C6)alkyl, cyano, the non-aromatic heterocycle, as defined in claim 1,
each of R8and R9independently represents hydrogen,
n is an integer from 0 to 3,
X10represents halogen or hydroxy, and
Rxrepresents hydrogen or a protective group for amino.



 

Same patents:

FIELD: medicine.

SUBSTANCE: invention refers to the compound 3-{[5-(azetidine-1-ylcarbonyl)pyrazine-2-yl] oxy}-5-{[(1S)-1-methyl-2-(methyloxy)ethyl]oxy}-N-(5-methylpyrazine-5-yl)benzamide or to its pharmaceutically acceptable salt. Also, it refers to a pharmaceutical composition for treating insulin-independent diabetes or obesity containing said compound.

EFFECT: there is produced and described a new compound which can be effective in treating insulin-independent diabetes and obesity.

5 cl, 64 ex

FIELD: chemistry.

SUBSTANCE: invention relates to oxazolidinone derivatives of formula (I) or pharmaceutically acceptable salts thereof, synthesis method thereof and pharmaceutical compositions containing said derivatives which are used as an antibiotic. Oxazolidinone derivatives, where R1 and R1' independently denote hydrogen or fluorine; R2 denotes -OR7, fluorine, monophosphate or metal phosphate; and R7 denotes hydrogen, C1-3alkyl or an acylated amino acid group, where the amino acid is alanine, glycine, proline, proline, isoleucine, leucine, phenylalanine, β-alanine or valine; R3 denotes hydrogen, a C1-4alkyl group which is unsubstituted or substituted cyano, , -(CH2)m-OR7 (m equals 0, 1, 2, 3, 4) or a ketone group. Oxazolidinone derivatives of formula (I) have antibacterial activity against different human and animal pathogens.

EFFECT: oxazolidinone derivatives, having inhibiting activity towards a wide range of bacteria and having low toxicity.

27 cl, 4 tbl, 73 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of formula I and to their pharmaceutically acceptable salts. In formula I p is integer, equal to 0-1; L2 is selected from group including -XOX-, -XSX- and -XSXO-; where X is independently selected from group, including bond and C1-C4alkylene; R13 is selected from group, including halogen, C1-C6alkyl, C1-C6alkoxygroup, -C(O) C1-C6alkyl; R14 is selected from group, including -XOXC(O)OR17 and -C1-C4alkylene-C(O)OR17; where X represents bond or C1-C4alkylene; and R17 is selected from group, including hydrogen and C1-C6alkyl; R15 and R16 are independently selected from group, including -R18 and -YR18; where Y represents C2-C6alkenylene, and R18 is selected from group, including C6-C10aryl, benzo[1,3]dioxolyl, pyridinyl, pyrimidinyl, quinolyl, phenoxatiinyl, benzofuranyl, dibenzofuranyl, benzoxasolyl, 2,3-dihydrobenzofuranyl, 2-oxo-2,3-dihydrobenzooxasolyl, indolyl, 3-oxo-3,4-dihydro-2H-benzo[1,4]oxazinyl, 2,3-dihydrobenzo[1,4]dioxinyl, 3,4-dihydro-2H-benzo[b][1,4]dioxepinyl, where any C6-C10aryl, pyridinyl, benzoxasolyl, indolyl in R18 is optionally substituted by 1-2 radicals, independently selected from group, including halogen, nitrogroup, cyanogroup, C1-C6alkyl, C1-C6alkoxygroup, C1-C6alkylthiogroup, hydroxy-C1-C6alkyl, halogen-substituted C1-C6alkyl, halogen-substituted C1-C6alkoxygroup, piperidinyl, morpholinyl, pyrrolidinyl, phenyl, XS(O)0-2R17, -XNR17R17, -XNR17S(O)2R17, -XNR17C(O)R17, -XC(O)NR17R17, -XC(O)NR17R19, -XC(O)R17, -XC(O)R19 and -XOXR19, where X represents bond; R17 is selected from group, including hydrogen, C1-C6alkyl, halogen-substituted C1-C6alkyl, and R19 is selected from group, including C3-C12cycloalkyl, phenyl, piperidinyl, morpholinyl.

EFFECT: ensuring application of invention compounds for production of medication, modulating activity of activated receptors of peroxisome proliferators δ (ARPPδ), to pharmaceutical composition, possessing properties of ARPPδ activity modulator, including therapeutically efficient quantity of invention compound and to application of pharmaceutical composition for medication manufacturing.

8 cl, 1 tbl, 301 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I

, where R1 is selected from a group comprising hydrogen, lower alkyl, lower hydroxyl, lower alkoxyalkyl, lower halogenalkyl, lower cyanoalkyl; unsubstituted or substituted phenyl; lower phenylalkyl, where the phenyl ring can be unsubstituted or substituted; and heteroaryl, selected from pyridyl and pyrimidinyl; R2 denotes hydrogen or halogen; G denotes a group selected from

, where m equals, 0, 1; R3 is selected from lower alkyl, cycloalkyl and lower cycloalkylalkyl; n equals 0, 1; R4 denotes lower alkyl, as well as pharmaceutical compositions.

EFFECT: said compounds are used to treat or prevent diseases associated with histaminase receptor modulation.

19 cl, 1 tbl, 24 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula 1, its pharmaceutically acceptable salts and stereoisomers: $ (1), where: R1 means H, amidino, C1-C4-alkyl amidino, C1-C4alkanoylamidino, C1-C10-alkyl, C3-C7-cycloalkyl, C6-C10-aryl, 6-members heterocycle with O atom, 5-members heterocycle with two N atoms, 6-members heteroaryl with one or two N atoms, 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, C1-C6-alkylcarbonyl, C3-C7-cycloalkylcarbonyl, C1-C4-alkoxycarbonyl, C6-C10-aryl-C1-C4-alkoxycarbonyl, -SO2-C1-C4-alkyl, -C(O)-N(R6)(R7) or -C(S)-N(R6)(R7); and, R6, R7 means H, C1-C6-alkyl, C3-C7-cycloalkyl; alkyl, cycloalkyl, heterocycle, aryl or heteroaryl are unsubstituted or substituted; R2 means C6-C10-aryl which is unsubstituted or mono- or disubstituted; R3 means H, CN, C1-C6-alkyl, C3-C7-cycloalkyl, C2-C6-alkenyl, monocyclic 5-members heterocycle with N and O, monocyclic 5-members heteroaryl with two heteroatoms, one of which is N, and the other is O or S, C(O)-R8 or -C(S)-R8; and R8 means OH, C1-C4-alkyl, C1-C4-alkyloxy or N(R9)(R10); R9, R10 mean N, C1-C6-alkyl, C3-C7-cycloalkyl, C1-C4-alkyloxy, phenyl or 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, 6-members heteroaryl with N; R9, R10 together with N whereto attached can form a single 4-6-members ring which can include in addition O or S; and alkyl, cycloalkyl, heterocycle, phenyl or heteroaryl are unsubstituted or substituted. R4 means C3-C8-cycloalkyl, C6-C10-aryl, 5-members heteroaryl with two heteroatoms, one of which is N, and the other is S, 6-members heteroaryl with N, 6-members heterocycle with O, and C6-C10-aryl or heteroaryl are unsubstituted or mono- or polysubstituted. R5 means N, C1-C6-alkyl, -C(O)-R11, C1-C6-alkylsulphonyl, C6-C10-arylsulphonyl, -(CH2)p-C6-C10-aryl, -(CH2)p-heteroaryl or -(CH2)p-C3-C8-cycloalkyl where heteroaryl means 5-members heteroaryl with O or with N or with S which can contain in addition N. p is equal to 1 or 2; R11 means C1-C10-alkyl, C1-C6-alkenyl, C3-C8-cycloalkyl, C3-C8-cycloalkenyl, NH2, C1-C4alkylamino, (C1-C4-alkyl)(C1-C4-alkyl)amino, C6-C10-aryl, 5-members heteroaryl with N or with O or with 8 which can contain in addition N, 6-members heterocycle with N and O, 5- or 6-members heterocycle with O, and alkyl is unsubstituted or substituted with one substitute. Aryl, heteroaryl, cycloalkyl, cycloalkenyl or heterocycle are unsubstituted or mono- or disubstituted.

EFFECT: compounds are melanocortin receptor agonists so presented to be used in a pharmaceutical composition for treatment and prevention of obesity, diabetes, inflammation, erectile dysfunction.

19 cl, 18 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to novel derivatives of cis-2,4,5-triarylimidazoline of general formula I and pharmaceutically acceptable salts thereof, where X1 is selected from a group comprising lower alkoxy; X2 and X3 are independently selected from a group comprising hydrogen, halogen, cyano, lower alkyl, lower alkoxy, piperidinyl, -NX4X5, -SO2NX4X5, -C(O)NX4X5, -C(O)X6, -SOX6, -SO2X6, -NC(O)-lower alkoxy, -C≡C-X7, provided that both X2 and X3 do not denote hydrogen, lower alkyl or lower alkoxy, provided that when X2 or X3 denote hydrogen, the other does not denote lower alkyl, lower alkoxy or halogen, provided that when X2 denotes -HX4X5, X3 does not denote hydrogen, X2 and X3 together can form a ring selected from 5-7-member unsaturated rings which can contain three heteroatoms selected from S, N and O, X4 and X5 are independently selected from a group comprising hydrogen, lower alkyl, lower alkoxy, lower alkyl, substituted by a lower alkoxy, -SO2-lower alkyl, -C(O)piperazinyl-3-one; X6 is selected from a group comprising lower alkyl, morpholine, piperidine, pyrrolidine; X7 is selected from a group comprising hydrogen, lower alkyl, trifluoromethyl; Y1 and Y2 are independently selected from a group comprising halogen; R is selected from a group comprising lower alkoxy, piperidinyl substituted with a five-member heterocyclic ring which contains one nitrogen heteroatom, piperidinyl substituted with a hydroxy, -CH2OH or -C(O)NH2, piperazinyl substituted with one or two R1 [1,4]diazepanyl, substituted R1, R1 can denote one or two substitutes selected from a group comprising oxo, lower alkyl substituted with one R2, -C(O)R3, -SO2-lower alkyl, -SO2-five-memer heterocyclyl, which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl; R2 is selected from a group comprising -SO2-lower alkyl, hydroxy, lower alkoxy, -NH-SO2-lower alkyl, -cyano, -C(O)R4; R3 is selected from a group comprising a five-member heterocyclyl which is selected from isoxazolyl, dimethylisoxazolyl, pyrrolidinyl, pyrrolyl, thiophenyl, imidazolyl, thiazolyl, thiazolidinyl, imidazolidinyl, lower alkyl, lower alkenyl, lower alkyl substituted with a six-member heterocyclyl selected from piperidinyl, piperazinyl, 3-oxopiperazinyl, morpholinyl, C3-cycloalkyl; R4 is selected from a group comprising hydroxy, morpholine, piperidine, 4-acetylpiperazinyl, -NR5R6; R5 and R6 are independently selected from a group comprising hydrogen, lower alkyl, lower alkyl substituted with lower alkoxy or cyano, lower alkoxy and C3-cycloalkyl. The invention also relates to a pharmaceutical composition based on the formula I compound, use of the formula I compound in preparing a medicinal agent and a method for synthesis of the formula I compound.

EFFECT: novel derivatives of cis-2,4,5-triarylimidazoline of general formula I are obtained, which can be used to treat diseases, based on reaction of the MDM2 protein with p53-like protein, particularly as anticancer agent.

54 cl, 412 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to compounds of formula (I), where R1 denotes a 5- or 6-member ring of formulae

(II) or (III), respectively: R2 denotes H, C1-C7-alkyl, C3-C6-cycloalkyl or -(CH2)m,-Ra; R3 denotes aryl or heteroaryl, which can be substituted with CN, Cl, F, Br, CF3, CHF2, C3-C6-cycloalkyl or denotes heteroaryl which can be possibly substituted with C1-C7-alkyl; R4 denotes H, -OH, Cl, F, Br, CN, -CHF2, CF3, C1-C7-alkyl, C3-C6-cycloalkyl or -(CH2)m-Re; R5 denotes C1-C7-alkyl, -(CH2)n-O-Rf, or -(CH2)n-Re; Ra denotes -OH; Re denotes -OH; Rf denotes C1-C7-alkyl; m equals 1-4; n equals 2-6; and pharmaceutically acceptable salts thereof. The invention also relates to a medicinal agent containing said derivatives, use thereof in preparing medicinal agents suitable for treating diseases of the central nervous system.

EFFECT: novel compounds suitable for treating diseases of the central nervous system are obtained and described.

29 cl, 111 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to novel antibacterial compounds of formula (I). Compounds of formula (I) Q-NH-CO-R3, where Q stands for group of the following structure , R1 represents hydrogen, halogen, hydroxy, amino, mercapto, alkyl, heteroalkyl, alkeloxy, heteroalkyloxy, cycloalkyl, heterocycloalkyl, alkylcycloalkyl, heteroalkylcycloalkyl, cycloalkyloxy, alkylcycloalkyloxy, heterocycloalkyloxy or heteroalkylcycloalkyloxy, X1, X2, X3, X4, X5 and X6 each independently on each other represent nitrogen atom or group of formula CR2, R2 represents hydrogen, halogen or hydroxy, amino, alkyl, alkenyl, alkinyl or heteroalkyl group, R3 is selected from the following groups R5 represents group of formula -B-Y, where B represents alkylene, alkenylene, alkinylene, -NH- or heteroalkylene, and Y represents aryl, heteroaryl, aralkyl, heteroaralkyl, cycloalkyl, heterocycloalkyl, alkylcycloalkyl or heteroalkylcycloalkyl, or their pharmaceutically acceptable salt, solvate, hydrate or pharmaceutically acceptable composition, as well as to pharmaceutical composition, which possesses antibacterial activity, based on said compounds and to their application for preparation of medication, intended for treatment of bacterial infections.

EFFECT: obtained and described are compounds, which can be useful in medicine.

9 cl, 147 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: medicine.

SUBSTANCE: compounds of the invention exhibit properties of β2- adrenoreceptor agonists. In formula (I) , R1 represents hydrogen; each R2, R3, R4, R5, R4' and R5' independently represents hydrogen or C1-C6alkyd; e is equal to 0 or 1; A represents C(O); D represents oxygen or sulphur; m is equal to an integer 0 to 3; n is equal to an integer 0 to 3; R6 represents the group -(X)p-Y-(Z)q-R10; each X and Z independently represents C1-C6akylene group; each p and q is independently equal to 0 or 1; Y represents a bond, oxygen, CH2 or NR9; R7a and R7b independently represent hydrogen or C1-C6alkyl; R9 represents C1-C6alkyl; R10 represents hydrogen or saturated or unsaturated 6-members ring system optionally containing at least one ring heteroatom, chosen of nitrogen. And this ring system is optionally substituted by C1-C6alkoxycarbonyl; R7 represents 6-12-members aromatic ring system which is optionally substituted by halogen, trifluoromethyl, hydroxyl, C1-C6alkyl, C1-C6alkoxy or NH2; provided R6 does not represent hydrogen or unsubsituted C1-C6alkyl group. Also, the invention refers to methods for producing compounds of formula (I), to a pharmaceutical composition exhibiting properties of β2- adrenoreceptor agonists containing the compound of formula (I) as an active ingredient, to application of the compound of formula (I) in preparing a drug, to a combination containing the compound of formula (I) and one or more agents.

EFFECT: improved properties of the composition.

27 cl, 2 tbl, 32 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel derivatives of isothiazole-3(2H)-OH-1,1-dioxides of formula (I) or pharmaceutically acceptable salts thereof, which can increase expression of LXR α and/or β, a pharmaceutical composition based on said derivatives, use thereof in preparing a medicinal agent, as well as novel intermediate compounds of formula (V) or salts thereof. In formulae (I), (V) R2 denotes phenyl, and R1 and R3 are as described in the claim.

EFFECT: improved properties of the derivatives.

7 cl, 9 dwg, 172 ex

FIELD: chemistry.

SUBSTANCE: invention relates to crystalline forms of a hydrate of 5-(4-{[6-(4-amino-3,5-dimethylphenoxy)-1-methyl-1-H-benzimidazol-2-yl]methoxy}benzyl)-1,3-thiazolidine-2,4-dione dihydrochloride of formula (I). The invention also relates to methods for synthesis of said compounds and to pharmaceutical compositions based on said compounds, having PPARy activating property.

EFFECT: said forms of the compounds are more stable and can be used in medicine to prepare medicinal agents for treating diabetes, cancer accompanied by diabetes.

16 cl, 7 tbl, 5 dwg, 6 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new pyrrolidine derivatives of general formula (1) or its pharmaceutically acceptable salts where R101 and R102 values are described by the patent claim. The compounds inhibit serotonin and/or norepinephrine and/or dopamine reabsorption thereby allowing to be used for treating depression and anxiety disorder. A method for preparing thereof is described.

EFFECT: preparation of new pyrrolidine derivatives.

10 cl, 162 tbl, 7 ex

FIELD: chemistry.

SUBSTANCE: invention describes compounds of formula I

, where R1 is selected from a group comprising hydrogen, lower alkyl, lower hydroxyl, lower alkoxyalkyl, lower halogenalkyl, lower cyanoalkyl; unsubstituted or substituted phenyl; lower phenylalkyl, where the phenyl ring can be unsubstituted or substituted; and heteroaryl, selected from pyridyl and pyrimidinyl; R2 denotes hydrogen or halogen; G denotes a group selected from

, where m equals, 0, 1; R3 is selected from lower alkyl, cycloalkyl and lower cycloalkylalkyl; n equals 0, 1; R4 denotes lower alkyl, as well as pharmaceutical compositions.

EFFECT: said compounds are used to treat or prevent diseases associated with histaminase receptor modulation.

19 cl, 1 tbl, 24 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula [I-D1] or pharmaceutically acceptable salt thereof,

,

where each symbol is defined in the claim. The invention also relates to pharmaceutical compositions containing said compound and having HCV polymerase inhibiting activity.

EFFECT: disclosed compound exhibits anti-HCV activity, based on HCV polymerase inhibiting activity and is useful as an agent for preventing and treating hepatitis C.

32 cl, 497 tbl, 1129 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives of formula I

or pharmaceutically acceptable salts thereof, where R1 denotes (1-6C)alkyl; R2, R3 independently denote halogen, (1-4C)alkoxy; R4 denotes phenyl or a 5-6-member heteroaryl, having one or two heteroatoms selected from nitrogen, oxygen or sulphur, phenyl or said heteroaryl, substituted with R7 and optionally substituted on the (hetero)aromatic ring with one or two substitutes selected from halogen, nitro, trifluoromethyl and (1-4C)alkyl; R7 denotes H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R8R9-amino, R10R11-aminocarbonyl, R12R13-amino(1-4C)alkylcarbonyl-amino, R14R15-amino(1-4C)alkyl, R16-oxy, R17R18-aminocarbonyl (1-4C)alkoxy, R19-oxy(1-4C)alkyl, R19-oxycarbonyl(1-4C)alkyl, R20R21-aminosulphonyl, R20-oxysulphonyl, aminoiminomethyl, (di)(1-4C)alkylaminoiminomethyl, morpholinyliminomethyl, trifluoromethylsulphonyl; R23-oxycarbonyl, or R23R24-aminocarbonyl; R8 denotes H or (1-4C)alkyl; R9 denotes (1-4C)alkylsulphonyl, (1-6C)alkylcarbonyl, (2-6C)alkenylcarbonyl, (3-6C)cycloalkylcarbonyl, (1-4C)alkoxycarbonyl, (3-4C)alkenyloxycarbonyl, (di)(1-4C)alkylaminocarbonyl, piperazinylcarbonyl, (5-8C)alkyl, (3-6C)cycloalkyl(1-4C)alkyl or phenylcarbonyl, furylcarbonyl, thiophenylsulphonyl, 5-member heteraryl(1-4C)alkyl, having one or two nitrogen atoms, optionally substituted on the heteroaromatic ring with one, two or three substitutes selected from hydroxy, amino, halogen, nitro, trifluoromethyl, (1-4C)alkoxy; R10 denotes H or (1-4C)alkyl; R11 denotes hydroxy(2-4C)alkyl, (1-4C)alkoxy(2-4C)alkyl; R12, R13 independently denote H, (1-6C)alkyl, (3-6C)-cycloalkyl, (1-4C)alkoxy(2-4C)alkyl, (3-6C)cycloalkyl-(1-4C)alkyl, pyrrolidinyl(1-4C)alkyl, amino(2-4C)alkyl, (di)(1-4C)-alkylamino(2-4C)alkyl or phenyl(1-4C)alkyl, pyridinyl (1-4C)alkyl; or R12R13 in R12R13-amino(1-4C)alkylcarbonylamino can be bonded together with the nitrogen atom to which they are bonded into a (5-6C)heterocycloalkyl ring, having one or two nitrogen atoms, optionally substituted with hydroxy(1-4C)alkyl; R14, R15 independently denote H, (1-6C)alkyl, (1-6C)alkylcarbonyl, (1-4C)alkoxycarbonyl or pyridinyl(1-4C)alkyl, optionally substituted on the aromatic ring with one substitute selected from halogen; or R16 denotes (di)(1-4C)alkylamino(2-4C)alkyl, hydroxycarbonyl(1-4C)alkyl, (1-4C)alkoxycarbonyl(1-4C)alkyl, phenyl(1-4C)alkyl or pyridinyl(1-4C)alkyl; R17, R18 independently denote H, (1-6C)alkyl, thiophenyl(1-4C)alkyl; or R17R18 in R17R18-aminocarbonyl(1-4C)alkoxy can be bonded into a morpholine or piperazine ring, R19 denotes H or (1-6C)alkyl; R20R21 independently denote H, (1-6C)alkyl or (1-4C)alkoxy(1-4C)alkyl; or R20R21 in R20R21-aminosulphonyl can be bonded into a morpholine ring; X denotes O or N-R22; Y denotes CH2 or C(O); Z denotes CN or NO2; R22 denotes H; R23, R24 independently denotes H; (1-4C)alkyl; or R23R24 in R23R24-aminocarbonyl can be bonded into a dihydropyridine ring; provided that compounds of formula I, in which X denotes O, R4 denotes phenyl and R7 is selected from H, (1-4C)alkylthio, (1-4C)alkylsulphonyl, R23-oxycarbonyl, and R23R24-aminocarbonyl, and compounds of formula I, in which X denotes O, R4 denotes (2-5C)heteroaryl and R7 denotes H are excluded. The invention also relates to use of 4-phenyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline derivatives to prepare a medicinal agent for treating sterility.

EFFECT: improved useful biological properties.

12 cl, 73 ex

Organic compounds // 2411239

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula I, in which R1 denotes alkyl or cycloalkyl; R2 denotes phenyl-C1-C7-alkyl, di-(phenyl)- C1-C7-alkyl, naphthyl- C1-C7-alkyl, phenyl, naphthyl, pyridyl-C1-C7-alkyl, indolyl- C1-C7-alkyl, 1H-indazolyl- C1-C7-alkyl, quinolyl C1-C7-alkyl, isoquinolyl- C1-C7-alkyl, 1,2,3,4-tetrahydro-1,4-benzoxazinyl- C1-C7-alkyl, 2H-1,4-benzoxazin-3(4H)-onyl-C1-C7-alkyl, 9-xanthenyl-C1-C7-alkyl, 1-benzothiophenyl-C1-C7-alkyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 9-xanthenyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl, where each phenyl, naphthyl, pyridyl, indolyl, 1H-indazolyl, quinolyl, isoquinolyl, 1,2,3,4-tetrahydro-1,4-benzoxazonyl, 2H-1,4-benzoxazin-3(4H)-onyl, 1-benzothiophenyl, 4H-benzo[1,4]thiazin-3-only, 3,4-dihydro-1H-quinolin-2-onyl or 3H-benzoxazol-2-onyl are unsubstituted or contain one or up to 3 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy-C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkoxy-C1-C7-alkoxy- C1-C7-alkyl, C1-C7-alkanoyloxy- C1-C7-alkyl, amino- C1-C7-alkyl, C1-C7-alkoxy- C1-C7-alkylamino- C1-C7-alkyl, C1-C7-alkanoylamino- C1-C7-alkyl, C1-C7-alkylsulphonylamino- C1-C7-alkyl, carboxy- C1-C7-alkyl, C1-C7-alkoxycarbonyl- C1-C7-alkyl, halogen, hydroxy group, C1-C7-alkoxy group, C1-C7-alkoxy- C1-C7-alkoxy group, amino- C1-C7-alkoxy group, N-C1-C7-alkanoylamino-C1-C7-alkoxy group, carbamoyl- C1-C7-alkoxy group, N-C1-C7-alkylcarbamoyl-C1-C7-alkoxy group, C1-C7-alkanoyl, C1-C7-alkoxy-C1-C7-alkanoyl, C1-C7-alkoxy- C1-C7-alkanoyl, carboxyl, carbamoyl and N-C1-C7-alkoxy-C1-C7-alkylcarbamoyl; W denotes a fragment selected from residues of formulae IA, IB and IC, where () indicates the position in which the fragment W is bonded to the carbon atom in position 4 of the piperidine ring in formula I, and where X1, X2, X3, X4 and X5 are independently selected from a group containing carbon and oxygen, where X4 in formula IB and X1 in formula IC can assume one of these values or can be additionally selected from a group comprising S and O, where carbon and nitrogen ring atoms can include a number of hydrogen atoms or substitutes R3 or R4 if contained, taking into account limitations given below, required to bring the number of bonds of the carbon ring atom to 4 and 3 for the nitrogen ring atom; provided that in formula IA at least 2, preferably at least 3 of the atoms X1-X5 denote carbon and in formulae IB and IC at least one of X1-X4 denotes carbon, preferably 2 of the atoms X1-X4 denote carbon; y equals 0 or 1; z equals 0 or 1; R3, which can be bonded with any of the atoms X1, X2, X3 and X4, denotes hydrogen or a C1-C7-alkyloxy-C1-C7-alkyloxy group, phenyloxy-C1-C7-alkyl, phenyl, pyridinyl, phenyl- C1-C7-alkoxy group, phenyloxy group, phenyloxy-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, tetrahydropyranyloxy group, 2H,3H-1,4-benzodioxynyl-C1-C7-alkoxy group, phenylaminocarbonyl or phenylcarbonylamino group, where each phenyl or pyridyl is unsubstituted or contains one or up to 3 substitutes, preferably 1 or 2 substitutes independently selected from a group comprising C1-C7-alkyl, hydroxy group, C1-C7-alkoxy group, phenyl-C1-C7-alkoxy group, where phenyl is unsubstituted or substituted with a C1-C7-alkoxy group and/or halogen; carboxy- C1-C7-alkyloxy group, N-mono- or N,N-di-(C1-C7-alkyl)aminocarbonyl-C1-C7-alkyloxy group, halogen, amino group, N-mono- or N,N-di-(C1-C7-alkyl)amino group, C1-C7-alkanoylamino group, morpholino-C1-C7-alkoxy group, thiomorpholino-C1-C7-alkoxy group, pyridyl-C1-C7-alkoxy group, pyrazolyl, 4- C1-C7-alkylpiperidin-1-yl, tetrazolyl, carboxyl, N-mono- or N,N-di-(C1-C7-alkylamino)carbonyl or cyano group; or denotes 2-oxo-3-phenyltetrahydropyrazolidin-1-yl, oxetidin-3-yl-C1-C7-alkyloxy group, 3-C1-C7-alkyloxetidin-3-yl- C1-C7-alkyloxy group or 2-oxotetrahydrofuran-4-yl- C1-C7-alkyloxy group; provided that if R3 denotes hydrogen, then y and z are equal to 0; R4, if contained, denotes a hydroxy group, halogen or C1-C7-alkoxy group; T denotes carbonyl; and R11 denotes hydrogen, or pharmaceutically acceptable salts thereof. The invention also relates to use of formula I compounds, a pharmaceutical composition, as well as a method of treating diseases.

EFFECT: obtaining novel biologically active compounds having activity towards rennin.

11 cl, 338 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method for selective production of N-[3-(1,3,5-dithiazinan-5-yl)propyl]-N-[4-(1,3,5-dithiazinan-5-yl)butyl]amine and N1,N4-bis-[3-(1,3,5-dithiazinan-5-yl)propyl]-1,4-butane diamine which involves reaction of an amine with a hydrogen sulphide saturated aqueous solution of formaldehyde, where the amine used is polymethylenepolyamine (spermidine or spermine) in molar ratio polyamine: formaldehyde: hydrogen sulphide equal to 1:6:4 and the reaction is carried out at 20°C for 3 hours.

EFFECT: compounds can be used as selective sorbents and extraction agents of precious metals, special reagents for inhibiting bacterial activity in various media.

1 cl, 2 ex

FIELD: chemistry.

SUBSTANCE: described are novel derivatives of genera formula (1) (where A denotes an oxygen or sulphur atom, -CH2- or -NH- group; R1 denotes C1-6alkyl group, possibly substituted ; R1A denotes a hydrogen atom or a C1-6 alkyl group; or these two radicals together with a carbon atom to which they are bonded form a cyclic C3-6 alkyl group; R2 denotes a C1-6 alkyl group or a C3-6 cycloalkyl group; R3 denotes an aryl group or a heteroaryl group, which can be substituted; R4 denotes a hydrogen atom; R5 denotes C1-6 alkyl group, aryl or heteroaryl group, which can be substituted), a pharmaceutical composition containing said derivatives and intermediate compounds. Said compounds (1) can inhibit bonding between SIP and its receptor Edg-1 (SIP1).

EFFECT: possibility of use in medicine.

18 cl, 2 tbl, 28 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel AMPA receptor antagonists - 1H-quinazoline-2,4-dione derivatives, selected from the group: N-(6-imidazol-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,4]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrolidin-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-azetidin-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,3]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; (2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)amide ethanesulphonic acid; N-(6-imidazol-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-thiomorpholin-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(6-[1,4]oxazepan-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide and N-(6-azetidin-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide and physiologically acceptable salts thereof.

EFFECT: compounds can be used in treating such diseases as epilepsy and schizophrenia.

9 cl, 106 ex

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