Indole-3-carbonyl-spiro-piperadine derivatives as v1a receptor antagonists

FIELD: chemistry.

SUBSTANCE: invention relates to indol-3-yl-carbonyl-spiro-piperadine derivatives used as V1a receptor antagonists and which have formula I: , where the spiro-piperadine A head group and residues R1, R2 and R3 are as defined in claim 1 of the invention. The invention also pertains to pharmaceutical compositions which contain such compounds and use thereof in preparing medicines with V1a receptor antagonist activity.

EFFECT: high activity of derivatives.

37 cl, 1 tbl, 285 ex

 

The text descriptions are given in facsimile form.

1. Compounds of General formula (I)

where a is selected from the following groups (a), (b), (C), (d), (e), (f), (g) and (h):



where (a) the dashed line
is absent or represents a double bond;
R1represents H,
or represents a C1-6-alkyl, possibly substituted by a group CN or represents phenyl, pyridine or sulfonylated, possibly substituted by one or more than one,
or represents -(CH2)m-Rawhere Rais:
CN,
ORi,
NRiRii,
With3-6-cycloalkyl, 3-7-membered heteroseksualci (3 of compound 261), comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbor -(CH2 n-(SO2)-Rbwhere Rbis:
C1-6-alkyl,
C1-6-alkoxy,
NRiRii,
With3-6-cycloalkyl, 4-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or R1and R3together with the indole ring to which they are attached, form a 5 - or 6-membered heteroseksualci, which may be substituted by =O, C(O)O-C1-6-alkyl or C1-6-alkyl;
R2represents one or more than one of N, halogeno, C1-6-alkyl, C1-6-alkoxy,
or two R2can form a bridge oxo or dioxo together with the indole ring to which they are attached;
R3represents H,
or is halogen,
or represents -(CO)-Rcwhere Rcis:
C1-6-alkyl,
-(CH2)n-NRiRii,
-(CH2)n-NRiiiRiv,
5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, possibly substituted C1-6-alkyl,
or is a1-6-alkyl,
R4represents one or more che is one of H, halogeno,1-6-alkyl or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R5represents H, C1-6-alkyl or phenyl;
R6represents N or C1-6-alkyl;
R7represents H or-SO2-Rewhere Rerepresents a C1-6-alkyl;
R8represents N or C1-6-alkyl;
X represents CH2or C=O;
In is halogen, CN, NRiRiiWith1-6-alkyl, possibly substituted by a group CN, halogeno or1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, (CRiiiRiv)n-phenyl, where the phenyl group possibly substituted by one or more than one Deputy, selected from the group consisting of:
halogeno,1-6-alkyl, possibly substituted by a group of halogeno or C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2- C1-6-alkyl, -S(O)2- NRiiiRivor HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

2. The connection is of the General formula (I) according to claim 1, where
And selected from (a), (b), (C), (d), (e), (f), (g) or (h), where
R1represents H,
or is a1-6-alkyl, possibly substituted by a group CN or represents phenyl, pyridine or sulfonylated, possibly substituted by one or more than one,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbor -(CH2)n-(SO2)-Rbwhere Rbis:
With1-6-alkoxy,
NRiRii,
4-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one, or R1and R3together with the indole ring to which they are attached, form a 5 - or 6-membered heteroseksualci, which may be substituted by =O, C(O)O-C1-6-alkyl or C -alkyl;
R2represents one or more than one of N, halogeno,1-6-alkyl, C1-6-alkoxy;
R3represents H,
or is halogeno
or represents -(CO)-Rcwhere Rcis:
C1-6-alkyl,
-(CH2)n-NRiRii,
-(CH2)n-NRiiiRiv,
5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, possibly substituted C1-6-alkyl,
or represents a C1-6-alkyl,
R4represents one or more than one of N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R5represents H or phenyl;
R6represents H;
R7represents H or-SO2-Rewhere Rerepresents a C1-6-alkyl;
R8represents N or C1-6-alkyl;
X represents CH2or C=O;
In is halogen, CN, NH2With1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenylphosphino substituted by one or more than one Deputy, selected from the group consisting of:
halogeno, C1-6-alkyl, possibly substituted by a group of halogeno, C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, S(O)2-C1-6-alkyl or-S(O)2-NRiiiRivor HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

3. Compounds of General formula (I) according to claim 1,
where a is selected from groups (a), (b), (C), (d) and (e); and
R1represents H,
or represents a C1-6-alkyl, possibly substituted by a group CN or represents phenyl, pyridine or sulfonylated, possibly substituted by one or more than one,
or represents -(CH2)m-Rawhere Rais:
CN,
ORi,
NRiRii,
With3-6-cycloalkyl, 4-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbor -(CH2)n-(SO2)-Rbwhere Rbis:
C1-6-lkyl,
With1-6-alkoxy,
NRiRii,
With3-6-cycloalkyl, 4-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or R1and R3together with the indole ring to which they are attached, form a 5 - or 6-membered heteroseksualci, which may be substituted with group ();
R2represents one or more than one of N, halogeno, C1-6-alkyl, C1-6-alkoxy, or two of R2can form a bridge oxo or dioxo together with the indole ring to which they are attached;
R3represents H,
or is halogen,
or represents -(CO)-Rcwhere Rcis:
C1-6-alkyl,
-(CH2)n-NRiRii,
-(CH2)n-NRiiiRiv,
5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, possibly substituted C1-6-alkyl,
or is a1-6-alkyl;
R4represents one or more than one of N, halogeno,1-6-alkyl or C1-6-alkoxy, or two of R4can form a bridge oxo or dio is with together with the phenyl ring, to which they are attached;
R5represents H, C1-6-alkyl or phenyl;
R6represents N or C1-6-alkyl;
R7represents H or-SO2-Rewhere Rerepresents a C1-6-alkyl;
In is halogen, CN, NRiRiiWith1-6-alkyl, possibly substituted by a group CN, halogeno or1-6-alkoxy, C1-6-alkoxy, C1-6halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, (CRiiiRiv)n-phenyl, where the phenyl group possibly substituted by one or more than one Deputy, selected from the group consisting of:
halogeno, C1-6-alkyl, C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl - NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or-S(O)2- NRiiiRiv;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

4. Compounds of General formula (I) according to claim 1,
where a is selected from groups (a), (b), (C), (d) and (e);
and R1represents N or
C1-6-alkyl, possibly substituted by a group CN or
phenyl, or
pyridine, or
phenylsulfonyl or
-(CH2)m-Rawhere Rarepresents a C3-6-cycloalkyl, 5 - or 6-members of the hydrated heteroseksualci, comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one Deputy, selected from the group consisting of:
halogen, CN, C1-6-alkyl, C1-6-alkoxy, C1-6-halogenoalkane, -C(O)O-C1-6-alkyl and phenyl, possibly substituted by a group of halogeno, C1-6-alkyl, C1-6-halogenoalkanes or C1-6-alkoxy,
-(CH2)m-NRiRiior
-(CH2)n-(CO)-Rbwhere Rbrepresents phenyl or 5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen;
R2represents one or more than one of N, halogeno,1-6-alkyl, C1-6-alkoxy, or two of R2can form a bridge oxo or dioxo together with the indole ring to which they are attached;
R3represents N or
halogeno or
-(CO)-Rcwhere Rcrepresents a C1-6-alkyl, 5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, possibly substituted C1-6-alkyl, or Rcrepresents -(CH2)n-NRiRiior
C1-6-alkyl;
R4p is ecstasy one or more than one of N, halogeno, C1-6-alkyl or C1-6-alkoxy, or two of R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R5represents H, C1-6-alkyl or phenyl;
R6represents N or C1-6-alkyl;
R7represents H or-SO2-Rewhere Rerepresents a C1-6-alkyl;
Riand Riiindependently selected from H, C1-6-alkyl or -(CO)O-C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

5. Compounds according to claim 1 of formula (I-a)

where the dotted line is absent or represents a double bond and R1-R6are as defined in any one of claims 1 to 4.

6. Compounds according to claim 5 of the formula (1-a), where the dotted line is absent or represents a double bond;
R1represents H,
or is a1-6-alkyl, possibly substituted by a group CN,
or is phenylsulfonyl,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl, including the Dean or two heteroatoms, selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
With1-6-alkoxy,
NRiRii,
6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one;
R2represents one or more than one of N, halogeno,1-6-alkyl;
R3represents H,
or represents a C1-6-alkyl,
or represents -(CO)-Rcwhere Rcis:
With1-6-alkyl,
-(CH2)n-NRiRii,
R4represents one or more than one of N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R5represents H;
R6represents H;
In is halogen, CN, C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv) n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of: halogen,1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

7. Compounds according to claim 5 of the formula (I-a), where
the dotted line is absent or represents a double bond;
R1represents H,
or represents -(CH2)m-Rawhere Rarepresents phenyl, which is possibly substituted by one or more than one Deputy, selected from
the group consisting of:
halogen, CN, C1-6-alkyl, C1-6-alkoxy, C1-6-halogenoalkane, -C(O)O-C1-6-alkyl and phenyl, possibly substituted by a group of halogeno, C1-6-alkyl, C1-6-halogenoalkanes or1-6-alkoxy;
R2represents H or halogeno;
R3represents N or C1-6-alkyl; and
R4, R5and R6are H; m is 1-6;
and their pharmaceutically acceptable salts.

8. Compounds according to claim 5 of the formula (I-a)where specified with the unity selected from the group consisting of:
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]Spiro[inden-1,4'-piperidine];
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-2,3-dihydrospiro[inden-1,4'-piperidine];
1'-[(1-benzyl-1H-indol-3-yl)carbonyl]Spiro[inden-1,4'-piperidine];
1'-[(2-methyl-1H-indol-3-yl)carbonyl]Spiro[inden-1,4'-piperidine];
1'-[(6-chloro-1H-indol-3-yl)carbonyl]Spiro[inden-1,4'-piperidine]
1'-[(6-chloro-1H-indol-3-yl)carbonyl]-2,3-dihydrospiro[inden-1,4'-piperidine].

9. Compounds according to claim 1 of formula (I-b):

where R1, R2, R3, R4, R6and R7are as defined in any one of claims 1 to 4.

10. Compounds according to claim 9 of the formula (I-b), where
R1represents H,
or represents a C1-6-alkyl, possibly substituted by a group CN,
or is phenylsulfonyl,
or represents -(CH2)m-Rawhere Rais:
OR1
CN,
NRiRii,
With3-6-cycloalkyl, 3-6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
C1-6-alkoxy,
NR iRii,
5 - or 6-membered-heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one;
R2represents one or more than one of N, halogeno, C1-6-alkyl;
R3represents H,
or represents a C1-6-alkyl,
or represents -(CO)-Rcwhere Rcis:
C1-6-alkyl,
-(CH2)n-NRiRii,
R4represents one or more than one of N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R6represents H;
R7represents H or-SO2-Rewhere Rerepresents a C1-6-alkyl;
In is halogen, CN, C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of: halogen, C1-6-is Lila, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

11. Compounds according to claim 9 of the formula (I-b), where
R1represents H,
or represents -(CH2)m-Rawhere Rarepresents phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one Deputy, selected from the group consisting of: halogen, CN, C1-6-alkyl, C1-6-alkoxy, C1-6-halogenoalkane, -C(O)O-C1-6-alkyl and phenyl, possibly substituted by a group of halogeno,1-6-halogenoalkanes or1-6-alkoxy,
or represents -(CH2)m-NRiRii,
or represents -(CH2)n-(CO)-Rbwhere Rbrepresents phenyl or 5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rb iRii,
R2represents H or halogeno;
R3represents N or C1-6-alkyl;
R4represents H or halogeno;
R6represents H;
R7represents H or-SO2-Rewhere Rerepresents a C1-6-alkyl;
In is halogeno, NH2C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of: halogen,1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Ri, Riiindependently selected from N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

12. Compounds according to claim 9 of the formula (I-b), where these compounds are selected from the group consisting of the following compounds:
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-1-(methylsulphonyl)-1,2-dihydrospiro[indole-3,4'-piperidine];
1'-{[6-chloro-1-(3-perbenzoic)-1H-indol-3-yl]carbonyl}-1,2-dihydrospiro[indole-3,4'-piperidine];
1'-{[6-chloro-1-(2-perbenzoic)-1H-indol-3-yl]carbonyl}-1,2-dihydrospiro[indole-3,4'-piperidine];
1'-{[6-chloro-1-(3,5-differentail)-1H-indol-3-yl]carbonyl}-1,2-dihydro what pyro[indole-3,4'-piperidine];
1'-{[6-chloro-1-(2,3-differentail)-1H-indol-3-yl]carbonyl}-1,2-dihydrospiro[indole-3,4'-piperidine];
1'-({6-chloro-1-[(3,5-differenl)sulfonyl]-1H-indol-3-yl}carbonyl)-1,2-dihydrospiro[indole-3,4'-piperidine];
2-[6-chloro-3-(1,2-dihydro-1 N-Spiro[indole-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-1-(3,5-differenl)ethanone;
2-[6-chloro-3-(1,2-dihydro-1 N-Spiro[indole-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-1-(3,4-differenl)ethanone;
2-[6-chloro-3-(1,2-dihydro-1 N-Spiro[indole-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-1-(2-forfinal)ethanone;
2-[6-chloro-3-(1,2-dihydro-1 N-Spiro[indole-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-diethylethanamine and
1'-{[6-chloro-1-(pyridine-2-ylmethyl)-1H-indol-3-yl]carbonyl}-1,2-dihydrospiro[indole-3,4'-piperidine].

13. Compounds according to claim 1 of formula (I-c)

where R1-R4are as defined in any one of claims 1 to 4.

14. Connection 13 of the formula (I-c), where
R1represents H,
or represents a C1-6-alkyl, possibly substituted by a group CN or represents phenyl, pyridine or phenylsulfonyl, possibly substituted by one or more than one,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 4-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
C1-6-alkoxy,
NRiRii,
4-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or R1and R3together with the indole ring to which they are attached, form a 5 - or 6-membered heteroseksualci, which may be substituted by =O;
R2represents one or more than one of N, halogeno, C1-6-alkyl, C1-6-alkoxy;
R3represents H,
or represents a C1-6-alkyl,
or is halogen,
or represents -(CO)-Rcwhere Rcis:
With1-6-alkyl,
-(CH2)n-NRiRii,
-(CH2)n-NRiiiRiv,
5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, possibly substituted C1-6-alkyl;
R4represents one or more than Odie is from N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
In is halogeno, NH2With1-6-alkyl, possibly substituted by a group CN or C1-6alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of:
halogeno,1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv, -(CO)-C1-6-alkyl, -S(O)2-C1-6-alkyl, -S(O)2-NRiiiRiv;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

15. Connection 13 of the formula (1-c), where these compounds selected from the group consisting of:
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-6-chloro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-4-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-6-methoxy-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-ningal-3-yl)carbonyl]-5-methoxy-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-7-chloro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(6-chloro-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(6-chloro-1H-indol-3-yl)carbonyl]-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-N,N-dimethyl-1H-indole-2-carboxamide;
tert-butyl {2-[({6-chloro-3-[(6-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-2-yl}carbonyl)amino]ethyl}methylcarbamate;
6-chloro-N,N-diethyl-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1'4'-piperidine]-1'-yl)carbonyl]-1H-indole-2-carboxamide;
1'-{[6-chloro-2-(piperidine-1-ylcarbonyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-7H-Spiro[furo[3,4-f][1,3]benzodioxol-5,4'-piperidine]-7-it;
3-{6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}propanenitrile;
{6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}acetonitrile;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-6-(2-hydroxyethoxy)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3,5-differenl)-1H-indol-3-yl]carbonyl}-3H-is pyro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3,5-differentail)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3,5-diferensial)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3-terbisil)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(3-forfinal)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(2,5-differenl)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3,5-diferensial)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3-terbisil)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(3-forfinal)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
5-bromo-1'-{[6-chloro-1-(3,5-diferensial)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
5-bromo-1'-{[6-chloro-1-(3-terbisil)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
5-bromo-1'-({6-chloro-1-[2-(3-forfinal)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(2-forfinal)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(3,4-differenl)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(3-forfinal)-1H-indol-3-yl]carb the Nile}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(2-oxo-2-piperidine-1-retil)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(2-morpholine-4-yl-2-oxoethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
2-{6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}-N,N-dimethylacetamide;
2-{6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}-N,N-diethylacetamide;
1'-{[6-chloro-1-(piperidine-1-ylcarbonyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
tert-butyl{6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}acetate;
1'-[(6-chloro-1-pyridin-2-yl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(6-chloro-1-pyridin-2-yl-1H-indol-3-yl)carbonyl]-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(2-methylpyridin-4-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(6-chloropyridin-3-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(3-chloro-6-methylpyridazin-4-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(pyridine-4-ylmethyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(2-pyridin-4-retil)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'{[6-chloro-1-(pyridine-4-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(2-oxo-2-pyridin-2-retil)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(pyridine-2-ylmethyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
2-{6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}-N,N-dimethylacetamide;
1'-({6-chloro-1-[2-(dimethylamino)ethyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(pyridine-3-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(pyrazin-2-ylmethyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(pyrimidine-5-ylmethyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
3-{6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}propanenitrile;
tert-butyl{6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}acetate;
1'-{[6-chloro-1-(2-morpholine-4-yl-2-oxoethyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({1-[(4-benzylmorphine-2-yl)methyl]-6-chloro-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(5-methylisoxazol-3-yl)methyl]-1H-indol-3-yl}CT is of IMT-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[6-chloro-1-(pyridine-2-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(5-cyclopropyl-2-methyl-1,3-oxazol-4-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(1-methyl-1H-imidazol-5-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(3-methylisoxazol-5-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(1,5-dimethyl-1H-pyrazole-3-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(3,5-dimethylisoxazol-4-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(2,5-dimethyl-1,3-oxazol-4-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(3-Torosyan-3-yl)methyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-({6-chloro-1-[(3-Torosyan-3-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-[(6-chloro-1-{[1-(methoxymethyl)-cyclopropyl]methyl}-1H-indol-3-yl)carbonyl]-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
[1-({6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}methyl)cyclepro the yl]acetonitrile;
1'-[(6-chloro-1-{[1-(methoxymethyl)-cyclopropyl]methyl}-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
[1-({6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}methyl)cyclopropyl]acetonitrile;
1'-({6-chloro-1-[2-(tetrahydro-2H-Piran-4-yl)ethyl]-1H-indol-3-yl}carbonyl)-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one hydrochloride;
1'-({6-chloro-1-[2-(tetrahydro-2H-Piran-4-yl)ethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
tert-butyl 2-({6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}methyl)morpholine-4-carboxylate;
tert-butyl 2-({6-chloro-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}methyl)morpholine-4-carboxylate;
1'-{[6-chloro-1-(morpholine-2-ylmethyl)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one dihydrochloride;
1'-{[6-chloro-1-(morpholine-2-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro [2-benzofuran-1,4'-piperidine]-3-one hydrochloride;
2-{6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}ndimethylacetamide;
2-{6-chloro-3-[(5-fluoro-3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}-N-methylacetamide;
1'-{[6-chloro-1-(2-oxo-2-piperazine-1-retil)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
1'-{[1-(3,5-diferensial)-1H-indol-3-yl]carbonyl}-5-fluoro-3H-Spiro[2-Ben is furan-1,4'-piperidine]-3-one;
1'-{[1-(3,5-diferensial)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
N,N-diethyl-2-{3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}ndimethylacetamide and
2-{6-chloro-5-methyl-3-[(3-oxo-1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}-N,N-dimethylacetamide.

16. Connection pop formula (I-d)

where R1-R5are as defined in any one of claims 1 to 4.

17. Compounds according to article 16 of the formula (I-d), where
R1represents H,
or is a1-6-alkyl, possibly substituted by a group CN or represents phenyl, pyridine or phenylsulfonyl, possibly substituted by one or more than one,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-7-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
With1-6-alkoxy,
NRiRii,
4-7-membered heteroseksualci, including one or two gateroad the mA selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or R1and R3together with the indole ring to which they are attached, form a 5 - or 6-membered heteroseksualci, which may be substituted by C(O)O-C1-6-alkyl or C1-6-alkyl;
R2represents one or more than one of N, halogeno,1-6-alkyl, C1-6-alkoxy;
R3represents H,
or represents a C1-6-alkyl,
or represents -(CO)-Rcwhere Rcrepresents a C1-6alkyl or-
-(CH2)n-NRiRii;
R4represents one or more than one of N, halogeno or1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R5represents H or phenyl;
In is halogeno, NH2With1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected is from the group consisting of:
halogeno, C1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv, -C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl, -S(O)2- NRiiiRivor HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

18. Compounds according to article 16 of the formula (I-d), where these compounds selected from the group consisting of:
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-6-chloro-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(1-benzoyl-2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[2-methyl-1-(phenylsulfonyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[1-(cyclohexylmethyl)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[1-(3-terbisil)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({2-methyl-1-[2-(triptoreline)benzyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[1-(3,5-dimethylbenzyl)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
methyl-4-{[2-methyl-3-(1 N,3H-Spiro[2-benzofur the EN-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]methyl}benzoate;
4-{[2-methyl-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]methyl}benzonitrile;
1'-{[1-(3,5-diferensial)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[1-(2-Chlorobenzyl)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[1-(2-methoxybenzyl)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[1-(4-methoxybenzyl)-2-methyl-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(1-{[2-(2-methoxyphenyl)-5-methyl-1,3-oxazol-4-yl]methyl}-2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(1-benzyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(6-chloro-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
N,N-dimethyl-2-[3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethanamine;
2-methyl-1-[3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-2-yl]butane-1-it;
[6-chloro-3-(1H,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-yl carbonyl)-1H-indol-1-yl]acetonitrile;
1'-{[6-chloro-1-(3-perbenzoic)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(2-perbenzoic)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(3,5-differentail)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(2,3-differentail)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[6-chloro-1-(3,5-diferensial)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(3-terbisil)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(2-oxo-2-piperidine-1-retil)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(2-morpholine-4-yl-2-oxoethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-dimethylacetamide;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-diethylacetamide;
1'-{[6-chloro-1-(piperidine-1-ylcarbonyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
tert-butyl[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl] acetate;
1'-{[6-chloro-1-(3,5-differenl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(3-forfinal)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-1-(2-forfinal)ethanone;
1'-[(6-chloro-1-pyridin-2-yl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(pyridine-4-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-1-pyridin-2-yl of ethanone;
1'-{[6-chloro-1-(pyridine-3-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(pyridine-2-ylmethyl)-1H-indol-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(pyrazin-2-yl methyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(pyrimidine-5-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-dimethylethanamine;
1'-{[6-chloro-1-(2-oxo-2-piperazine-1-retil)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({1-[(4-benzylmorphine-2-yl)methyl]-6-chloro-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(5-methylisoxazol-3-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[2-(4-methylpiperazin-1-yl)-2-oxoethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
4-(1-{1-[(2-cyclopropyl-4-methylcyclopentene-1,4-Dien-1-yl)methyl]-6-methyl-1H-inden-3-yl}vinyl)-2',3'-dihydrospiro[cyclohexane-1,1'-inden];
1'-({6-chloro-1-[(1-methyl-1H-imidazol-5-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(3-methylisoxazol-5-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(1,5-dimethyl-1H-pyrazole-3-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(3,5-dimethylisoxazol-4-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(2,5-dimethyl-1,3-oxazol-4-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(3-ft is oxetan-3-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(6-chloro-1-{[1-(methoxymethyl)-cyclopropyl]methyl}-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
(1-{[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]methyl} cyclopropyl)acetonitrile;
1'-({6-chloro-1-[2-(tetrahydro-2H-Piran-4-yl)ethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro [2-benzofuran-1,4'-piperidine];
tert-butyl 2-{[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]methyl}morpholine-4-carboxylate;
1'-{[6-chloro-1-(morpholine-2-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine]hydrochloride;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N-[2-(dimethylamino)ethyl]ndimethylacetamide;
2-[6-chloro-5-methyl-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-dimethylacetamide;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ndimethylacetamide;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N-[2-(methylamino)ethyl]ndimethylacetamide;
N-(2-amino-ethyl)-2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ndimethylacetamide;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethanamine;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N-methylethanamine;
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N-methylacetamide;
1'-{[6-chloro-1-(3-morpholine-4-ylpropyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(oxiran-2-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethanol;
1'-({6-chloro-1-[(2-methylpyridin-4-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(3S)-piperidine-3-yl methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N-hydroxyethylamine;
1'-{[6-chloro-1-(tetrahydro-2H-Piran-4-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(1-methylpyrrolidine-3-yl)methyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(6-chloro-1-{[(3S)-1-methylpiperidin-3-yl]methyl}-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-{[6-chloro-1-(pyrrolidin-3-ylmethyl)-1H-indol-3-yl]carbonyl}-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-({6-chloro-1-[(2S)-pyrrolidin-2-ylmethyl]-1H-indol-3-yl}carbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(6-chloro-2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-(1,2,3,4-tetrahydropyrazino[1,2-a]indole-10-ylcarbonyl)-3H-Spiro[2-benzofuran-1,4'-piperidine]hydrochloride;
1'-[(2-methyl-1,2,3,4-tetrahydropyrazino[1,2-a]indol-10-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
1'-[(chlor-2-methyl-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine];
N-{2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethyl}ndimethylacetamide;
N-{2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethyl}methanesulfonamide;
N-{2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethyl}-N-methylacetamide;
N-{2-[6-chloro-3-(1 N,3H-Spiro[2-benzofuran-1,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]ethyl}-N-methylmethanesulfonamide;
1'-[(6-chloro-1-{[(2S)-1-methylpyrrolidine-2-yl]methyl}-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine]
1'-[(6-chloro-1-{[(2R)-1-methylpyrrolidine-2-yl]methyl}-1H-indol-3-yl)carbonyl]-3H-Spiro[2-benzofuran-1,4'-piperidine].

19. Compounds according to claim 1 of formula (I-e)

where R1, R2, R3, R4and R6are as defined in any one of claims 1 to 4.

20. Compounds according to claim 19 of the formula (1-e), where
R1represents H,
or is a1-6-alkyl, possibly substituted by a group CN,
or is phenylsulfonyl,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from color is Yes, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
C1-6-alkoxy,
NRiRii,
5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one;
R2represents one or more than one of N, halogeno,1-6-alkyl;
R3represents H,
or represents a C1-6-alkyl,
or represents -(CO)-Rcwhere Rcis:
With1-6-alkyl,
-(CH2)n-NRiRii,
R4represents one or more than one of N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R6represents H;
In is halogen, CN, C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or is more than one Deputy, selected from the group consisting of:
halogeno, C1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

21. Compounds according to claim 19 of the formula (1-e), where
R1represents N or
-(CH2)m-Rawhere Rarepresents 5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur,
-(CH2)m-NRiRiior
-(CH2)n-(CO)-Rbwhere Rbrepresents 5 - or 6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen;
R2represents one or more than one of N or halogeno;
R3represents H or is a1-6-alkyl;
R4represents one or more than one of N or halogeno;
R6represents H;
Riand Riirepresent1-6-alkyl;
m is 1-6;
n RA is but 0-4;
and their pharmaceutically acceptable salts.

22. Compounds according to claim 19 of the formula (I-e), where these compounds selected from the group consisting of:
1'-[(6-chloro-1H-indol-3-yl)carbonyl]Spiro[1-benzofuran-3,4'-piperidine];
1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]Spiro[1-benzofuran-3,4'-piperidine];
1'-(1H-indol-3-ylcarbonyl)Spiro[1-benzofuran-3,4'-piperidine];
1'-[(6-chloro-5-fluoro-1H-indol-3-yl)carbonyl]Spiro[1-benzofuran-3,4'-piperidine];
2-[6-chloro-3-(1 N-Spiro[1-benzofuran-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-dimethylethanamine;
1'-{[6-chloro-1-(2-pyrrolidin-1-retil)-1H-indol-3-yl]carbonyl}Spiro[1-benzofuran-3,4'-piperidine];
3-[6-chloro-3-(1 N-Spiro[1-benzofuran-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-DIMETHYLPROPANE-1-amine;
1'-{[6-chloro-1-(2-morpholine-4-retil)-1H-indol-3-yl]carbonyl}Spiro[1-benzofuran-3,4'-piperidine];
2-[6-chloro-3-(1 N-Spiro[1-benzofuran-3,4'-piperidine]-1'-ylcarbonyl)-1H-indol-1-yl]-N,N-diethylethanamine;
1'-({6-chloro-1-[2-(1H-pyrrol-1-yl)ethyl]-1H-indol-3-yl}carbonyl)Spiro[1-benzofuran-3,4'-piperidine]
1'-{[6-chloro-1-(2-oxo-2-piperidine-1-retil)-1H-indol-3-yl]carbonyl}Spiro[1-benzofuran-3,4'-piperidine].

23. Compounds according to claim 1 of formula (I-f)

where R1, R2, R3and R4are as defined in any one of claims 1 to 4.

24. Compounds according to item 23 of the formula (I-f), where
R1represents H,
or is Soboh the C 1-6-alkyl, possibly substituted by a group CN,
or is phenylsulfonyl,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
C1-6-alkoxy,
NRiRii,
6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one;
R2represents one or more than one of N, halogeno,1-6-alkyl;
R3represents H,
or represents a C1-6-alkyl,
or represents -(CO)-Rcwhere Rcis:
C1-6-alkyl,
-(CH2)n-NRiRii,
R4represents one or more than one of N, halogeno, or C1-6-alkoxy, possibly substituted by g is uppoi HE or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
In is halogen, CN, C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of: halogen, C1-6-alkyl, possibly substituted by a group of halogeno or C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

25. Compounds according to item 23 of the formula (I-f), where
R1represents H;
R2represents one or more than one of N or halogeno;
R3represents H;
R4represents one or more than one of N or halogeno;
and their pharmaceutically acceptable salts.

26. Compounds according to item 23 of the formula (1-f), where these compounds selected from the group consisting of:
5-bromo-1'-(1H-indol-3-ylcarbonyl)Spiro[indole-3,4'-piperidine]-2(1H)-it
5-bromo-1'-[(6-chloro-1H-Indo) - Rev.-3-yl)carbonyl]Spiro[indole-3,4'-piperidine]-2(1H)-it.

27. Compounds according to claim 1 of formula (I-g)

where R1, R2, R3and R4are as defined in any one of claims 1 to 4.

28. Compounds according to item 27 of the formula (I-g), where
R1represents H,
or is a1-6-alkyl, possibly substituted by a group CN,
or is phenylsulfonyl,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
With1-6-alkoxy,
NRiRii,
6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, aryl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one;
R2represents one or more than one of N, halogeno,1-6-alkyl;
R3represents H,
or is sobeys 1-6-alkyl,
or represents -(CO)-Rcwhere Rcis:
C1-6-alkyl,
-(CH2)n-NRiRii,
R4represents one or more than one of N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
In is halogen, CN, C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkane,3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of: halogen,1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

29. Compounds according to item 27 of the formula (I-g), where
R1represents N or
-(CH2)m-Rawhere Rarepresents phenyl;
R2represents one or more than one of N or Galaga is about;
R3represents H,
or is a1-6-alkyl;
R4represents H;
R6represents H;
and their pharmaceutically acceptable salts.

30. Compounds according to item 27 of the formula (I-g), where these compounds selected from the group consisting of:
(SS,RR)-1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-3',5'-dimethyl-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
(RS,SR)-1'-[(6-chloro-1H-indol-3-yl)carbonyl]-3',5'-dimethyl-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one;
(RS,SR)-1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-3',5'-dimethyl-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one and
(1R,3'R,5'S)-1'-[(1-benzyl-2-methyl-1H-indol-3-yl)carbonyl]-3',5'-dimethyl-3H-Spiro[2-benzofuran-1,4'-piperidine]-3-one.

31. Compounds according to claim 1 of formula (I-h)

where R1, R2, R3, R4, R8and X are as defined in any one of claims 1 to 4.

32. Connection p formula (I-h), where
R1represents H,
or is a1-6-alkyl, possibly substituted by a group CN,
or is phenylsulfonyl,
or represents -(CH2)m-Rawhere Rais:
ORi,
CN,
NRiRii,
With3-6-cycloalkyl, 3-6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered g is tetraaryl, comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one,
or represents -(CH2)n-(CO)-Rbwhere Rbis:
C1-6-alkoxy,
NRiRii,
6-membered heteroseksualci comprising one or two heteroatoms, selected from nitrogen and oxygen, phenyl or 5 - or 6-membered heteroaryl comprising one or two heteroatoms selected from oxygen, nitrogen and sulfur, which may be substituted by one or more than one;
R2represents one or more than one of N, halogeno, C1-6-alkyl;
R3represents H,
or represents a C1-6-alkyl,
or represents -(CO)-Rcwhere Rcis:
With1-6-alkyl,
-(CH2)n-NRiRii,
R4represents one or more than one of N, halogeno or C1-6-alkoxy, possibly substituted by a group of IT, or two R4can form a bridge oxo or dioxo together with the phenyl ring to which they are attached;
R8represents N or C1-6-alkyl;
X represents CH2or C=O;
In is halogen, CN, C1-6-alkyl, possibly substituted by a group CN or C1-6-alkoxy, C1-6-alkoxy, C1-6-halogenoalkanes is, With3-6-cycloalkyl, -C(O)O-C1-6-alkyl, -(CRiiiRiv)n-phenyl, where phenyl possibly substituted by one or more than one Deputy, selected from the group consisting of: halogen,1-6-alkyl, possibly substituted by a group of halogeno, and C1-6-alkoxy;
Riand Riirepresent H, C1-6-alkyl, C1-6-alkyl-NRiiiRiv-C(O)-C1-6-alkyl, -S(O)2-C1-6-alkyl or HE;
Riiiand Rivrepresent N or C1-6-alkyl;
m is 1-6;
n is 0-4;
and their pharmaceutically acceptable salts.

33. Connection p formula (I-h), where
R1represents H,
or represents -(CH2)n-(CO)-Rbwhere Rbrepresents NRiRii;
R2represents one or more than one of N or halogeno;
R3represents H;
R4represents H;
R8represents N or C1-6-alkyl;
X represents CH2or C=O;
Riand Riirepresent N or C1-6-alkyl;
and their pharmaceutically acceptable salts.

34. Connection p formula (I-h), where these compounds selected from the group consisting of:
1'-[(6-chloro-1H-indol-3-yl)carbonyl]Spiro[isoindole-1,4'-piperidine]-3(2H)-she;
1'-[(6-chloro-1H-indol-3-yl)carbonyl]-2-methyl-2,3-dihydrospiro[IsoIn the ol-1,4'-piperidine];
1'-[(6-chloro-1H-indol-3-yl)carbonyl]-2,3-dihydrospiro[isoindole-1,4'-piperidine]
2-{6-chloro-3-[(3-oxo-2,3-dihydro-1 N-Spiro[isoindole-1,4'-piperidine]-1'-yl)carbonyl]-1H-indol-1-yl}-N-methylacetamide.

35. The compound according to any one of claims 1 to 34 of the formula (I), (I-a), (I-b), (I-c), (I-d), (I-e), (I-f), (I-g) or (I-h)with the activity of the V1a receptor antagonist.

36. Pharmaceutical composition having activity of the V1a receptor antagonist containing one or more than one compound of formula (I), (I-a), (I-b), (I-C), (I-d), (I-e), (I-f), (I-g) or (I-h) no to any one of claims 1 to 34 and a pharmaceutically acceptable carrier.

37. The use of the compounds of formula (I), (I-a), (I-b), (I-C), (I-d), (I-e), (I-f), (I-g) or (I-h) according to any one of claims 1 to 34 for the manufacture of drugs with activity of the V1a receptor antagonist.



 

Same patents:

FIELD: medicine, pharmaceutics.

SUBSTANCE: tricyclic compounds of formula I: $ substituted with heterocycle are disclosed, or pharmaceutically acceptable salt or solvate of specified compound, isomer or racemic mixture, where stands for optional double link, dotted line stands for link or does not stand for link, which results in double or single link according to requirements of valency and where A, B, G, M, X, J, n, Het, R3, R10, R11, R32 and R33 and other substituents are such as indicated in formula of invention. Invention also relates to pharmaceutical compositions, which contain them, method of thrombin receptor or cannabinoid receptor inhibition, and to method for treatment of disease related to thrombosis, atherosclerosis, restenosis, hypertension, stenocardia, arrhythmia, cardiac failure and cancer by administration of specified compounds.

EFFECT: production of compounds having properties of antagonists of thrombin receptors.

33 cl, 6 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: use of compounds of formula (I): where: X denotes >CR1R2 or, when R6 denotes H, X denotes >SO2; Y denotes >CR1R2; Z denotes >C=O, >CH2, single bond; R1 denotes H, R2 denotes H, -COOH, -OH; or R1 and R2 together denote =O, ethylenedioxy or hydroxyimino group; R3 denotes H, lower alkyl group; R4 denotes two H, =O, hydroxyimino group; R5 denotes H, lower alkyl group, halogen; R6 denotes H, lower alkoxy, COOH; R7 and R8 are identical or different from each other and each denotes H, lower alkyl, halogen; and pharmaceutically acceptable salts thereof and esters for preparing a medicinal agent.

EFFECT: agent having neuroprotective action against hypoxia.

2 tbl, 24 ex, 13 cl

FIELD: chemistry.

SUBSTANCE: invention describes novel benzothiazinone derivatives of formula (I) and their use as antibacterial agents in infectious diseases caused by bacteria, especially mycobacterium tuberculosis (TB) and leprosy, in which R1 and R2 independently denote NO2, CN, CONR7R8, COOR9 CHO, halogen, SO2NR7R8, OCF3, trifluromethyl; R3 and R4 independently denote H or methyl; R5 and R6 independently denote a straight or branched aliphatic radical having 1-8 members in the chain, or R5 and R6 together denote a divalent radical -(CR92)m- or R5 and R6 together denote a divalent radical: R7, R8 and R9 independently denote H or a straight or branched aliphatic radical having 1-7 members in the chain, or phenyl.

EFFECT: design of an efficient method of obtaining benzothiazinone derivatives, a pharmaceutical composition having anti-mycobacterial activity.

12 cl, 6 tbl, 12 ex

FIELD: chemistry.

SUBSTANCE: invention relates to inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), their enatiomers, racemates and pharmaceutically acceptable salts, as well as a pharmaceutical composition based on said inhibitors and method of treating, preventing or suppressing inflammation and other conditions which are mediated by activity of leukotriene A4-hydrolase. In general formula (II) , X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is O; Z is chosen from a group which consists of O and a bond; W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to the nitrogen atom which is bonded to the said W; R4 is chosen from a group which consists of H, OCH3 and Cl; R6 is H or F; and R2' and R3' are each independently chosen from a group which consists of: A) H, C1-7alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-7alkyl, where each of substitutes (A) is independently substituted with 0 or 1 RQ, where each of said RQ is a carbon atom substitute, which is at least one carbon atom, separate from nitrogen atom; B) HetRa substitute; C) -C1-7alkyl-C(O)Rx; H) -C0-4alkyl-Ar5, where Ar5 is a 5-member heteroaryl, which has one heteroatom, chosen from a group >NRY, and 0 or 1 additional heteroatom -N=, and optionally contains two carbonyl groups, and optionally benzo-condensed; I) -C0-4alkyl-Ar5' , where Ar5' is a 5-member heteroaryl, which contains 3 or 4 nitrogen atoms; M) SO2C1-4alkyl; alternatively, R2' and R3', taken together with a nitrogen atom with which they are bonded, form a heterocyclic ring which contains at least one heteroatom, which is the said bonded nitrogen atom, where the said heterocyclic ring is chosen from a group which consists of i) 4-7-member heterocyclic ring HetRb, where the said 4-7-member heterocyclic ring HetRb has one heteroatom, which is the said bonded nitrogen atom, and is substituted with 0, 1 or 2 identical or different substitutes, where the said substitutes are chosen from a group which consists of -RY, -CN, -C(O)RY, -C0-4alkyl-CO2RY, -C0-4alkyl-C(O)CO2RY, -C0-4alkyl-ORY, -C0-4alkyl-C(O)NRYRZ-, -C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY, -C0-4alkyl-NRYCO2RY, -C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4alkyl-NRWSO2RY, 1,3-dihydrobenzoimidazol-2-on-1-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol- 5-yl, -C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY, -C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, , ,; ii) 5-7-member heterocyclic ring HetRC which has one additional heteroatom separated from the said bonded nitrogen atom by at least one carbon atom, where the said additional heteroatom is chosen from a group which consists of O, S(=O)2 and >NRM, where the said 5-7-member heterocyclic ring HetRC has 0 or 1 carbonyl group and is substituted with 0, 1 or 2 substitutes at identical or different substituted carbon atoms, where the said substitutes are chosen from a group which consists of -C(O)RY and RZ; iii) one of 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl is substituted at the carbon atom by 0 or 1 substitute such as -C0-4alkyl-RZ, -C0-4alkyl-CO2RY; and iv) one of benzimidazol-1-yl, 2,8-diazospiro[4.5]decan-1-on-8-yl, 4-{[(2-tert-butoxycarbonylaminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 4-{[(2-aminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 9-yl-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid, 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl, and where substitute HetRa is a 6-member heterocyclic ring, with a carbon atom at the bonding site and contains a >NRM group as a heteroatom, where the said heteroatom is separated from the said carbon atom at the bonding site with at least 1 additional carbon atom; Rk is chosen from a group which consists of H and -C1-4alkyl; RL is chosen from a group which consists of -CO2RS; RS is hydrogen; RM is chosen from a group which consists of RZ, -C(O)RY; RN is chosen from a group which consists of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3 and NO2; RQ is chosen from a group which consists of -CN, -C0-4alkyl-ORY, -C0-4alkyl-CO2RY, -C0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY; RW is chosen from a group which consists of RY; RX is chosen from a group which consists of -ORY, -NRYRZ, -C1-4alkyl and -C1-4alkyl-RAr; RY is chosen from a group which consists of H, C1-4alkyl, -C0-4alkyl-RAr and -C0-4alkyl-RAr', each of which is substituted with 1 or 2 RN substitutes; RZ is chosen from a group which consists of RY, -C1-2alkyl-CO2RY ; RAr is a radical with a carbon atom at the bonding position, where the said radical is chosen from a group which consists of phenyl, pyridyl and pyrazinyl, where each carbon atom with permissible valence in each of the said groups is independently substituted with at least 0, 1 or 2 RN or 0 or 1 RL; RAr' is a 5-6-member ring which has 1 or 2 heteroatoms, chosen from a group which consists of O, S, N and >NRY, and has 0 or 2 unsaturated bonds and 0 or 1 carbonyl group, where each member with permissible valence in each of the said rings is independently substituted with 0 or 1 or 2 RK; Description is given of inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), a composition which contains these inhibitions, and their use for inhibiting activity of the LTA4H enzyme, as well as for treating, preventing or suppressing inflammation and/or conditions which are associated with such inflammation. In the said formula (I): X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is chosen from a group which consists of CH2 and O, W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to a nitrogen atom; R4 is chosen from a group which consist of H, OCH3, CI, F, Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently chosen from different groups.

EFFECT: new compounds have useful biological activity.

43 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: invention relates to new a compound of formula I or formula II, or to its pharmaceutically acceptable salts, I II, where X is S; R1 is H or C1-C6alkyl; R2 is NR5R6; R3 is aryl, substituted with a halogen; R4 is H; R5 is H; R6 is H; R7 is CH2NR8R9 where R8 is H, C1-C10alkyl, C3-C8cycloalkyl, aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), heterocycle(C1-C6alkyl), heterocycle(C2-C6alkenyl), hydroxyl(C1-C6alkyl), hydroxyl(C2-C6alkyl), C1-C6alkoxycarbonyl, aryl(C1-C6alkoxy)carbonyl, carbamoyl(C1-C6alkyl); where the above mentioned aryl is an aromatic ring and is not substituted or substituted with one to three substituting groups, each of which, independently from the others, is chosen from: methylenedioxy, hydroxy, C1-C6-alkoxy, halogen, C1-C6alkyl, trifluoromethyl, trifluoromethoxy, NO2, NH2, NH(C1-C6alkyl), N(C1-C6alkyl)2, NH-acyl, N(C1-C6alkyl)-acyl, hydroxy(C1-C6alkyl), dihydroxy(C1-C6alkyl), CN, C(=O)O(C1-C6alkyl), phenyl, phenyl(C1-C6alkyl), phenyl(C1-C6alkenyl), phenoxy and phenyl(C1-C6alkoxy), R9 is H, C1-C10alkyl, heterocycle(C1-C6alkyl) or heterocycle(C2-C6alkenyl); where the above mentioned heterocycle represents a 5-member saturated monocyclic ring system, consisting of carbon atoms, as well as heteroatoms, chosen from a group comprising N, O, and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes NO2, aryl(C1-C6alkyl), arylsulphonyl; or R8 and R9 together with nitrogen, to which they are bonded, form a heterocycle, which represents a 5 - 7-member saturated monocyclic ring system, consisting of carbon atoms, as well as one to three heteroatoms, chosen from a group comprising N, O and S, which can be unsubstituted or have one to three substituting groups, independently chosen from a list which includes C1-C6alkoxy, hydroxy, C1-C6alkyl, C2-C6-alkenyl, C(=O)O(C1-C6alkyl), C(=O)NH2, C(=O)NH(C1-C6alkyl), C(=O)N(C1-C6-alkyl)2, hydroxy(C1-C6alkyl), dihydroxy(C2-C6alkyl), aryl, aryl(C1-C6alkyl), aryl(C2-C6alkenyl), aryl(C1-C6alkoxy) and pyrimidin-2-yl; and m equals 0. The invention also relates to a pharmaceutical composition, as well as to use of formula I or formula II compounds.

EFFECT: obtaining new biologically active compounds, with inhibitory properties towards casein kinase 1ε.

32 cl, 3 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds -(Z)-1'-R-6',6'-dimethyl-3-(phenyl(arylamino)methylene)-6',7'-dihydro-3H-spiro[furane-2,3'-indol]-2',4,4',5(1'H,5'H)-tetraons of formula: , where Ar=phenyl, n-methoxyphenyl, n-tollyl; R=allyl, benzyl, phenyl, n-tollyl, n-methoxyphenyl, α-naphtyl, as well as to method of their obtaining, which consists in the following: isopropyl 2-(1-aryl-4,5-dioxo-2-phenyl-4,5-dihydro-1H-pyrrol-3-yl)-2-oxoacetates are subjected to interaction with N-substituted 3-amino-5,5-dimethylcyclohex-2-enons in medium of inert aprotonic solvent with further separation of target products. Process is carried out at temperature 20-22°C. As solvent, absolute chloroform is used.

EFFECT: obtaining compounds possessing analgesic activity.

4 cl, 2 tbl, 2 ex

FIELD: chemistry.

SUBSTANCE: invention is related to compounds of formula (II) as inhibitor of leukotriene A4-hydrolase (LTA4H) and their enantiomers, racemic compounds and pharmaceutically acceptable salts, and also to treatment methods, method inhibition and pharmaceutical composition on their basis. In general formula (II) , X is selected from group that consists of O and S; Y is selected from group that consists of CH2 and O; R4 represents H; R6 represents H or F; and R2' is determined as R2, and R3' is determined as R3, as follows: R2 and R3, each, is independently selected from group that consists of A) H, C1-7alkyl, C3-7cycloalkyl, where each of substitutes of A) is independently substituted with 0 or 1 RQ, and each of mentioned RQ is substitute at carbon, which is distanced from nitrogen at least by one carbon atom; alternatively, R2 and R3, taken together with nitrogen, to which they are connected, create heterocyclic ring, which contains at least one heteroatom, which is specified nitrogen of connection, and specified heterocyclic ring is selected from group that consists of i) (4-7)-member heterocyclic ring HetRb, where specified (4-7)-member heterocyclic ring HetRb has single heteroatom, which is specified nitrogen of connection, and 0, 1 or 2 are substituted by substitutes at the same or different substituted atoms, at that specified substitutes are selected from group that consists of -RY, -C(O)RY, -C0-4alkylCO2RY, -C0-4alkylC(O)NRYRZ, -C0-4alkylNRYC(O)Rz, -C0-4alkylNRYC(O)CH2ORY, -C0-4alkylNRYCO2RY, -C0-4alkylNRYC(O)NRYRz, -C0-4alkylNRyC(S)NRyRz, -NRyC(O)CO2Ry, -C0-4alkylNRwSO2RY, tetrazol-5-yl, -C0-4alkylN(RY)(SO2)NRYRY, -C0-4alkylN(RY)(SO2)NRYCO2RY, ii) (5-7)-member heterocyclic ring HetRc, where specified (5-7)-member heterocyclic ring has single additional heteroatom distanced from specified nitrogen of connection at least by one carbon atom, thereat the specified additional heteroatom is selected from group that consists of O, S(=O)0-2 and >NRM, and where mentioned (5-7)-member heterocyclic ring HetRc has 0 or 1 carbonyl group; iv) one of 2,8-diazaspyro[4.5]decan-1-on-8-yl, 4-{[(2-tret- butoxycarbonylaminocyclobutancarbonyl)amino]methyl}-piperidine-1-yl, 4-{[(2-aminocyclobutancarbonyl)amino]methyl}piperidine-1-yl, tret-butyl ether of 3,9-diazaspyro [5.5]undecan-3-carbonic acid-9-yl; where RK is selected from group that consists of H, -C1-4alkyl, each not necessarily substituted by 1 substitute RN; RM is selected from group that consists of -SO2RY, -C(O)RY, -C(O)C1-4alkylORY, each not necessarily substituted by 1 substitute RN; RN is selected from group that consists of OH, NH2, CF3; RQ is selected from group that consists of -C0-4alkylRAr', -C0-4alkylCO2RY, -C0-4alkylNRYRz, -C0-4alkylNRYCORY, -C0-4alkylNRyCONRyRz; Rw is selected from group that consists of RY and -C3-7cycloalkyl; RY is selected from group that consists of H, -C1-4alkyl, -C0-4alkylRAr and -C0-4alkylRAr', each not necessarily substituted by 1 substitute RN; Rz is selected from group that consists of RY, -C1-2alkylCO2RY; RAr represents fragment connected via carbon atom, and specified fragment is selected from phenyl, pyridyl; RAr' represents (5-6)-member cyclic ring, having 1 or 2 heteroatoms selected from group that consists of O, N and >NRY, having 0 unsaturated connections, having 0 or 1 carbonyl group, where each atom, when allows for valency, in every of mentioned cyclic rings is independently substituted by 0 or 1 RK; provided that (a) specified R2' and R3', moreover, satisfy the following requirements: (e1): specified R2' and R3', both, are not H, when Y represents O and X represents S; (e3): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperazine group, when X represents O and Y is one of O and CH2; (e4): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperidine group, which is mono-substituted by 6-member cyclic group, when X represents O and Y is one of O and CH2; and (e5): specified R2' and R3', taken together with nitrogen, with which they are connected, create neither substituted piperidine group or substituted piperazine group, where specified substituted piperidine group or specified substituted piperazine group is substituted in position 4 by substitute XG, at that specified XG has structure , where n=0, 1, and when ne=1, then XL represents C1-6alkyl, OSG represents O or S, and XR1 and XR2, taken together with nitrogen, with which they are connected, create one of piperidine group, piperazine group, morpholine group, thiomorpholine group and pyrrolidine group, or each of XR1 and XR2, taken independently, represent one of H, C1-6alkyl, aryl, aralkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, heteroalkyl, heteroaryl-C1-6alkyl, heterocycloalkyl and heterocycloalkyl-C1-6alkyl; where aryl, aralkyl, cycloalkyl, heteroaryl or heterocycloalkyl may be not necessarily substituted by one or several substitutes, independently selected from halogen, hydroxy, C1-6alkyl, C1-6alkoxy, halogenated C1-6alkyl, halogenated C1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or heterocycloalkyl; and (b) further provided that when X represents S and Y represents O, then one of R2' and R3' is not XCG, while the other represents C1-6alkyl, where XCG represents group , where HC16 represents one of H, C1-6alkyl, halogenC1-6alkyl, allyl and C1-6alcoxymethyl, and GO represents group connected to carbon atom, which has substitute =0, creating amido group with nitrogen, with which all mentioned GO group is connected.

EFFECT: compounds may find application for treatment and prevention of diseases mediated by LTA4H, for instance, asthma, chronic obstructive lung disease, atherosclerosis, rheumatoid arthritis, disseminated sclerosis, inflammatory disease of bowels and psoriasis.

39 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: present invention relates to new compounds, and more specifically to 5-formyl-substituted indoline spirobenzopyrans with general formula 1 where R1, R2 - Alk or c-Alk; R3 -CHO or NO2 group (electron-acceptor substitute), with photochromic properties. The invention also relates to the method of producing 5-formyl substituted derivatives of indoline spirobenzopyrans with formula 1. Spirobenzopyrans, which have electron-acceptor substitutes in the pyran part of the molecule, are subjected to direct selective formylation in position 5 in a trifluoroacetic acid medium with urotropine (hexamethylenetetramine) at boiling point of the mixture in an inert atmosphere for 1-1.5 hours. The obtained 5-formyl-substituted spirobenzopyrans are photochromic compounds are photochromic and can be used for making new photochromic materials (recording devices or information storage; photo-switching activity of biological objects and polymer matrices, complex formation; information security media, maps, special document protection equipment) or as advanced initial compounds for further synthesis of a large number of new photochromic objects.

EFFECT: wider field of application of the compounds.

2 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: present invention pertains to a compound with general formula where R' stands for phenyl, unsubstituted or substituted with one or more substitutes, chosen from a group comprising alkyl, alkoxy group, halogen, -(CH2)oOH, -C(O)H, CF3, CN, S-alkyl, -S(O)1,2-alkyl, -C(O)NR'R", -NR'R"; R2 and R3 independently stand for hydrogen, halogen, alkyl, alkoxy group, OCHF2, OCH2F, OCF3 or CF3 and R4 and R5 independently stand for hydrogen, -(CH2)2SCH3, -(CH2)2S(O)2CH3, -(CH2)2S(O)2NHCH3, -(CH2)2NH2, -(CH2)2NHS(O)2CH3 or -(CH2)2NHC(O)CH3, R' stands for hydrogen, alkyl, -(CH2)oOH, -S(O)2- alkyl, -S(O)-alkyl, -S-alkyl; R" stands for hydrogen or alkyl; o stands for 0, 1, 2 or 3. The invention also relates to use of formula I compounds in making medicinal preparations for treating schizophrenia, for treating positive and negative symptoms of schizophrenia and medicine for treating schizophrenia.

EFFECT: obtaining new compounds with useful biological properties.

55 cl, 421 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention pertains to new compounds with general formula: , where R is -(CH2)n-A, where A: where each of B and C independently represent phenyl or phenyl substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, -OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NH-C(O)-(C1-C6alkyl) and -NO2; or n equals an integer from 0 to 3; n1 equals an integer from 1 to 3; n2 equals an integer from 0 to 4; n3 equals an integer from 0 to 3; n4 equals an integer from 0 to 2; X1 is chosen from a chemical bond -S-, -S(O)2-, -NH-, -NHC(O)- and -C=C-, R1 is chosen from C1-C6alkyl, C1-C6fluoroalkyl, C3-C6cycloalkyl, tetrahydropyranyl, CN, -N(C1-C6alkyl)2, phenyl, pyridinyl, pyrimidinyl, furyl, thienyl, naphtyl, morpholinyl, triazolyl, pyrazolyl, piperidinyl, pyrrolidinyl, imidazolyl, piperizinyl, thiazolydinyl, thiomopholinyl, tetrazolyl, benzoxazolyl, imidazolidine-2-thionyl, 7,7-dimethylbicyclo[2.2.1]heptane-2-onyl, benzo[1.2.5]oxadiazolyl, 2-oxa-5-azabicyclo[2.2.1]heptyl and pyrrolyl, each of which can be optionally substituted with 1-3 substitutes, independently chosen from a halogen, -CN, -CHO, -CF3, OCF3, -OH, -C1-C6alkyl, C1-C6alkoxy, -NH2, -N(C1-C6alkyl)2, -NH(C1-C6alkyl), -NO2, -SO2(C1-C3alkyl), -SO2NH2, -SO2N(C1-C3alkyl)2, -COOH, -CH2-COOH, pyridyl, 2-methylazolyl, morpholino, 1-chloro-2-methylpropyl, phenyl, (optionally substituted with one or more halogens), benzyloxy, and , X2 selected from -O-, -CH2-, -S-, -SO-, -SO2-, -NH- and , R2 represents a ring group, chosen from a phenyl or thienyl group. Each ring group is substituted with a group with formula -(CH2)n4-CO2H; and besides that, the ring group can optionally be substituted with 1 or 2 extra substitutes, independently chosen from halogen, - C1-C6alkyl and -C1-C6alkoxy; R3 is chosen from H, halogen and -NO2; R4 is chosen from H, halogen and morpholino; or its salt form, used in pharmaceuticals. The invention also relates to pharmaceutical compositions, to methods of treatment, and to compounds with formula (A).

EFFECT: obtaining new biologically active compounds and pharmaceutical compositions based on them, which have inhibiting effect on cytosolic phospholipase A2.

45 cl, 300 ex

FIELD: chemistry.

SUBSTANCE: described are spirocyclic derivatives of cyclohexane of general formula . Values of radicals are given in the formula of invention. The compounds have affinity to the ORL1 receptor and can be used for treating abstinence syndrome (withdrawal syndrome) and pain. Also described is a medicinal agent and use of formula (I) compounds for preparing respective medicinal agents.

EFFECT: increased effectiveness of using the compounds.

13 cl, 17 ex, 1 dwg

FIELD: chemistry.

SUBSTANCE: invention relates to inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), their enatiomers, racemates and pharmaceutically acceptable salts, as well as a pharmaceutical composition based on said inhibitors and method of treating, preventing or suppressing inflammation and other conditions which are mediated by activity of leukotriene A4-hydrolase. In general formula (II) , X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is O; Z is chosen from a group which consists of O and a bond; W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to the nitrogen atom which is bonded to the said W; R4 is chosen from a group which consists of H, OCH3 and Cl; R6 is H or F; and R2' and R3' are each independently chosen from a group which consists of: A) H, C1-7alkyl, C3-7cycloalkyl, C3-7cycloalkyl-C1-7alkyl, where each of substitutes (A) is independently substituted with 0 or 1 RQ, where each of said RQ is a carbon atom substitute, which is at least one carbon atom, separate from nitrogen atom; B) HetRa substitute; C) -C1-7alkyl-C(O)Rx; H) -C0-4alkyl-Ar5, where Ar5 is a 5-member heteroaryl, which has one heteroatom, chosen from a group >NRY, and 0 or 1 additional heteroatom -N=, and optionally contains two carbonyl groups, and optionally benzo-condensed; I) -C0-4alkyl-Ar5' , where Ar5' is a 5-member heteroaryl, which contains 3 or 4 nitrogen atoms; M) SO2C1-4alkyl; alternatively, R2' and R3', taken together with a nitrogen atom with which they are bonded, form a heterocyclic ring which contains at least one heteroatom, which is the said bonded nitrogen atom, where the said heterocyclic ring is chosen from a group which consists of i) 4-7-member heterocyclic ring HetRb, where the said 4-7-member heterocyclic ring HetRb has one heteroatom, which is the said bonded nitrogen atom, and is substituted with 0, 1 or 2 identical or different substitutes, where the said substitutes are chosen from a group which consists of -RY, -CN, -C(O)RY, -C0-4alkyl-CO2RY, -C0-4alkyl-C(O)CO2RY, -C0-4alkyl-ORY, -C0-4alkyl-C(O)NRYRZ-, -C0-4alkyl-NRYC(O)RZ-, -C(O)NRZORY, -C0-4alkyl-NRYCO2RY, -C0-4alkyl-NRYC(O)NRYRY, -C0-4alkyl-NRYC(S)NRYRZ, -NRYC(O)CO2RY, -C0-4alkyl-NRWSO2RY, 1,3-dihydrobenzoimidazol-2-on-1-yl, 1-RY-1H-tetrazol-5-yl, RY-triazolyl, 2-RY-2H-tetrazol- 5-yl, -C0-4alkyl-C(O)N(RY)(SO2RY), -C0-4alkyl-N(RY)(SO2)NRYRY, -C0-4alkyl-N(RY)(SO2)NRYCO2RY, halogen, , ,; ii) 5-7-member heterocyclic ring HetRC which has one additional heteroatom separated from the said bonded nitrogen atom by at least one carbon atom, where the said additional heteroatom is chosen from a group which consists of O, S(=O)2 and >NRM, where the said 5-7-member heterocyclic ring HetRC has 0 or 1 carbonyl group and is substituted with 0, 1 or 2 substitutes at identical or different substituted carbon atoms, where the said substitutes are chosen from a group which consists of -C(O)RY and RZ; iii) one of 1H-tetrazol-1-yl, where 1H-tetrazol-1-yl is substituted at the carbon atom by 0 or 1 substitute such as -C0-4alkyl-RZ, -C0-4alkyl-CO2RY; and iv) one of benzimidazol-1-yl, 2,8-diazospiro[4.5]decan-1-on-8-yl, 4-{[(2-tert-butoxycarbonylaminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 4-{[(2-aminocyclobutanecarbonyl)amino]methyl}piperidin-1-yl, 9-yl-tert-butyl ether 3,9-diazaspiro[5.5]undecane-3-carboxylic acid, 4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-8-yl, and where substitute HetRa is a 6-member heterocyclic ring, with a carbon atom at the bonding site and contains a >NRM group as a heteroatom, where the said heteroatom is separated from the said carbon atom at the bonding site with at least 1 additional carbon atom; Rk is chosen from a group which consists of H and -C1-4alkyl; RL is chosen from a group which consists of -CO2RS; RS is hydrogen; RM is chosen from a group which consists of RZ, -C(O)RY; RN is chosen from a group which consists of OCH3, CI, F, Br, I, OH, NH2, CN, CF3, CH3 and NO2; RQ is chosen from a group which consists of -CN, -C0-4alkyl-ORY, -C0-4alkyl-CO2RY, -C0-4alkyl-NRYRY, -C0-4alkyl-NRYCORY, -C0-4alkyl-NRYCONRYRZ, -C0-4alkyl-NRYSO2RY; RW is chosen from a group which consists of RY; RX is chosen from a group which consists of -ORY, -NRYRZ, -C1-4alkyl and -C1-4alkyl-RAr; RY is chosen from a group which consists of H, C1-4alkyl, -C0-4alkyl-RAr and -C0-4alkyl-RAr', each of which is substituted with 1 or 2 RN substitutes; RZ is chosen from a group which consists of RY, -C1-2alkyl-CO2RY ; RAr is a radical with a carbon atom at the bonding position, where the said radical is chosen from a group which consists of phenyl, pyridyl and pyrazinyl, where each carbon atom with permissible valence in each of the said groups is independently substituted with at least 0, 1 or 2 RN or 0 or 1 RL; RAr' is a 5-6-member ring which has 1 or 2 heteroatoms, chosen from a group which consists of O, S, N and >NRY, and has 0 or 2 unsaturated bonds and 0 or 1 carbonyl group, where each member with permissible valence in each of the said rings is independently substituted with 0 or 1 or 2 RK; Description is given of inhibitors of leukotriene A4-hydrolase (LTA4H) of formula (II), a composition which contains these inhibitions, and their use for inhibiting activity of the LTA4H enzyme, as well as for treating, preventing or suppressing inflammation and/or conditions which are associated with such inflammation. In the said formula (I): X is chosen from a group which consists of NR5, O and S, where R5 is one of H and CH3; Y is chosen from a group which consists of CH2 and O, W is chosen from a group which consists of CH2 and CHR1-CH2, where R1 is H or OH, and where the carbon group bonded to R1 in the said CHR1-CH2 is not directly bonded to a nitrogen atom; R4 is chosen from a group which consist of H, OCH3, CI, F, Br, OH, NH2, CN, CF3 and CH3; R6 is H or F; and R2 and R3 are each independently chosen from different groups.

EFFECT: new compounds have useful biological activity.

43 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: invention is related to compounds of formula (II) as inhibitor of leukotriene A4-hydrolase (LTA4H) and their enantiomers, racemic compounds and pharmaceutically acceptable salts, and also to treatment methods, method inhibition and pharmaceutical composition on their basis. In general formula (II) , X is selected from group that consists of O and S; Y is selected from group that consists of CH2 and O; R4 represents H; R6 represents H or F; and R2' is determined as R2, and R3' is determined as R3, as follows: R2 and R3, each, is independently selected from group that consists of A) H, C1-7alkyl, C3-7cycloalkyl, where each of substitutes of A) is independently substituted with 0 or 1 RQ, and each of mentioned RQ is substitute at carbon, which is distanced from nitrogen at least by one carbon atom; alternatively, R2 and R3, taken together with nitrogen, to which they are connected, create heterocyclic ring, which contains at least one heteroatom, which is specified nitrogen of connection, and specified heterocyclic ring is selected from group that consists of i) (4-7)-member heterocyclic ring HetRb, where specified (4-7)-member heterocyclic ring HetRb has single heteroatom, which is specified nitrogen of connection, and 0, 1 or 2 are substituted by substitutes at the same or different substituted atoms, at that specified substitutes are selected from group that consists of -RY, -C(O)RY, -C0-4alkylCO2RY, -C0-4alkylC(O)NRYRZ, -C0-4alkylNRYC(O)Rz, -C0-4alkylNRYC(O)CH2ORY, -C0-4alkylNRYCO2RY, -C0-4alkylNRYC(O)NRYRz, -C0-4alkylNRyC(S)NRyRz, -NRyC(O)CO2Ry, -C0-4alkylNRwSO2RY, tetrazol-5-yl, -C0-4alkylN(RY)(SO2)NRYRY, -C0-4alkylN(RY)(SO2)NRYCO2RY, ii) (5-7)-member heterocyclic ring HetRc, where specified (5-7)-member heterocyclic ring has single additional heteroatom distanced from specified nitrogen of connection at least by one carbon atom, thereat the specified additional heteroatom is selected from group that consists of O, S(=O)0-2 and >NRM, and where mentioned (5-7)-member heterocyclic ring HetRc has 0 or 1 carbonyl group; iv) one of 2,8-diazaspyro[4.5]decan-1-on-8-yl, 4-{[(2-tret- butoxycarbonylaminocyclobutancarbonyl)amino]methyl}-piperidine-1-yl, 4-{[(2-aminocyclobutancarbonyl)amino]methyl}piperidine-1-yl, tret-butyl ether of 3,9-diazaspyro [5.5]undecan-3-carbonic acid-9-yl; where RK is selected from group that consists of H, -C1-4alkyl, each not necessarily substituted by 1 substitute RN; RM is selected from group that consists of -SO2RY, -C(O)RY, -C(O)C1-4alkylORY, each not necessarily substituted by 1 substitute RN; RN is selected from group that consists of OH, NH2, CF3; RQ is selected from group that consists of -C0-4alkylRAr', -C0-4alkylCO2RY, -C0-4alkylNRYRz, -C0-4alkylNRYCORY, -C0-4alkylNRyCONRyRz; Rw is selected from group that consists of RY and -C3-7cycloalkyl; RY is selected from group that consists of H, -C1-4alkyl, -C0-4alkylRAr and -C0-4alkylRAr', each not necessarily substituted by 1 substitute RN; Rz is selected from group that consists of RY, -C1-2alkylCO2RY; RAr represents fragment connected via carbon atom, and specified fragment is selected from phenyl, pyridyl; RAr' represents (5-6)-member cyclic ring, having 1 or 2 heteroatoms selected from group that consists of O, N and >NRY, having 0 unsaturated connections, having 0 or 1 carbonyl group, where each atom, when allows for valency, in every of mentioned cyclic rings is independently substituted by 0 or 1 RK; provided that (a) specified R2' and R3', moreover, satisfy the following requirements: (e1): specified R2' and R3', both, are not H, when Y represents O and X represents S; (e3): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperazine group, when X represents O and Y is one of O and CH2; (e4): specified R2' and R3', taken together with nitrogen, with which they are connected, do not create piperidine group, which is mono-substituted by 6-member cyclic group, when X represents O and Y is one of O and CH2; and (e5): specified R2' and R3', taken together with nitrogen, with which they are connected, create neither substituted piperidine group or substituted piperazine group, where specified substituted piperidine group or specified substituted piperazine group is substituted in position 4 by substitute XG, at that specified XG has structure , where n=0, 1, and when ne=1, then XL represents C1-6alkyl, OSG represents O or S, and XR1 and XR2, taken together with nitrogen, with which they are connected, create one of piperidine group, piperazine group, morpholine group, thiomorpholine group and pyrrolidine group, or each of XR1 and XR2, taken independently, represent one of H, C1-6alkyl, aryl, aralkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-6alkyl, heteroalkyl, heteroaryl-C1-6alkyl, heterocycloalkyl and heterocycloalkyl-C1-6alkyl; where aryl, aralkyl, cycloalkyl, heteroaryl or heterocycloalkyl may be not necessarily substituted by one or several substitutes, independently selected from halogen, hydroxy, C1-6alkyl, C1-6alkoxy, halogenated C1-6alkyl, halogenated C1-6alkoxy, nitro, cyano, amino, C1-4alkylamino, di(C1-4alkyl)amino, heteroaryl or heterocycloalkyl; and (b) further provided that when X represents S and Y represents O, then one of R2' and R3' is not XCG, while the other represents C1-6alkyl, where XCG represents group , where HC16 represents one of H, C1-6alkyl, halogenC1-6alkyl, allyl and C1-6alcoxymethyl, and GO represents group connected to carbon atom, which has substitute =0, creating amido group with nitrogen, with which all mentioned GO group is connected.

EFFECT: compounds may find application for treatment and prevention of diseases mediated by LTA4H, for instance, asthma, chronic obstructive lung disease, atherosclerosis, rheumatoid arthritis, disseminated sclerosis, inflammatory disease of bowels and psoriasis.

39 cl, 8 tbl, 12 dwg, 484 ex

FIELD: chemistry.

SUBSTANCE: invention concerns novel derivatives of diazaspiropiperidine of the formula I: , where A-B is -CH2-CH2-, -CH2-O- or -O-CH2-; X is hydrogen or hydroxy; R1 is aryl optionally substituted by one or more substitutes selected out of group including haloid, (lower) alkyl, cyano, CF3, -OCF3, (lower) alkoxy, -SO2-(lower)alkyl, or heteroaryl with two nitrogen atoms; R2 is phenyl optionally substituted by one or more substitutes selected out of group including haloid, (lower) alkyl, CF3 or (lower) alkoxy; R3 is hydrogen or (lower)alkyl; n is 0, 1 or 2; and their pharmaceutically acceptable salts.

EFFECT: medicine based on compounds of the formula 1 and their application in obtaining medicine for neuropathological and neuropsychiatric disease treatment.

12 cl, 1 tbl, 29 ex

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula (1) where: R1 represents hydrogen atom, halogen, CP3, (1-3C)alkoxy group, m is an integer within 1 to 4, provided when m is equal to 2, 3 or 4, R1 substitutes can be either identical or different, R2 represents hydrogen atom, alkyl (1-6C) group optionally substituted with alkoxy group, cycloalkyl (3-6C) group, -CH2OH, -CH2OCH3, acetyl group, benzyl group optionally substituted with amino group, or group Q of the following composition (2): were: [ ]n symbolically represents -(CH2)n-, where n is an integer within 0 to 7, R3 represents hydrogen atom or alkyl (1-3C) group, R4 represents hydrogen atom, alkyl (1-6C) group optionally substituted with one or more groups, chosen of alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkoxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, amido group dialkyl, carboxyl group, saturated, unsaturated or partially saturated mono- or dicyclic 5-10-meroud ring optionally substituted with one or more groups, chosen of alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkyloxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, dialkylamido group, carboxyl group, or alkyl (1-3C) group substituted with saturated, unsaturated or partially saturated five- or hexamerous ring optionally containing one or more heteroatoms, such as nitrogen atom, oxygen atom or sulphur atom, optionally substituted with one or more groups chosen from alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkyloxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, dialkylamido group, carboxyl group, or (R3+R4) together with nitrogen atom, they are attached to, represent saturated, unsaturated or partially saturated mono- or dicyclic five- or hexamerous ring optionally containing one or more heteroatoms, such as nitrogen atom, oxygen atom or sulphur atom, optionally substituted with one or more groups chosen of alkyl group, aryl group, fluorine, chlorine, bromine, hydroxyl group, alkyloxy group, aryloxy group, acyloxy group, amino group, alkylamino group, dialkylamino group, arylamino group, thio group, alkylthio group, arylthio group, cyano group, oxo group, nitro group, acyl group, amido group, alkylamido group, dialkylamido group, carboxyl groups, as well as to all stereoisomers, to pharmaceutically acceptable salts. Additionally, the invention concerns pharmaceutical compositions and application of compounds.

EFFECT: production of new biologically active compounds with agonist activity to ORL1 receptors.

9 cl, 488 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of general formula where A-B stands for CH2-CH2, -CH2-O-, -O-CH2-, -CH2-S-, -S-CH2-, -N(R4)-CH2- or -CH2-N(R4)-; R1 stands for (lower)alkyl, (lower)alkenyl, cycloalkyl or stands for aryl, optionally substituted with one or two substitutes chosen from the group consisting of haloid, cyano, (lower)alkyl, CF3, OCF3 or (lower)alkoxy, or stands for heteroaryl representing cyclic aromatic hydrocarbon radical containing one or two heteroatoms chosen of the group consisting of sulphur or nitrogen, e.g. thiazolyl or thienyl, optionally substituted with one or two substitutes chosen from (lower)alkyl; R2 stands for (lower)alkyl, cycloalkyl or stands for aryl, optionally substituted with one or two substitutes chosen from the group consisting of haloid, (lower)alkyl, CF3, (lower)alkoxy, or stands for heteroaryl representing cyclic aromatic hydrocarbon radical containing one sulphur heteroatom, e.g. thienyl; R3 stands for hydrogen; R4 stands for hydrogen or benzyl; n stands for 0, 1 or 2; and to their pharmaceutically acceptable salts. Besides, the invention concerns a medical product.

EFFECT: production of new biologically active compounds inhibiting glycine carrier 1 (GlyT-1).

19 cl, 59 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: compounds of the invention have chemokine antagonistic properties and can be applied in treatment of immunoinflammatory diseases, such as atherosclerosis, allergy diseases. In general formula (I) R1 is hydrogen atom, (C1-C4)-alkyl, (C1-C4)-alkoxyl, cyclopropylmethoxy group, (C1-C4)-alkylthio group; R2 is halogen atom, (C1-C8)-alkyl, perfluoro-(C1-C4)-alkyl, (C3-C10)-cycloalkyl, phenyl, (C1-C8)-alkoxyl, values of the other radicals are indicated in the claim of the invention.

EFFECT: improved properties.

14 cl, 7 tbl, 20 dwg, 17 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to compounds of the formula (I): their using (variants) for preparing a drug used in treatment of diseases modulation of activity of chemokine receptors is useful, and to a pharmaceutical composition modulating chemokine receptors and comprising abovementioned compound. In compound of the formula (I) m = 0 or 1; R1 means halogen atom; X, Y and Z represent independently a bond, -CH2- or -O-, or X and Y form in common -CH=C(CH3)- or -C(CH3)=CH- under condition that only one radical among X, Y and Z can represents a bond, and under condition that X and Y both don't represent -O- simultaneously; n = 0, 1 or 2; R2 represents halogen atom, or (C1-C6)-alkyl; q = 0 or 1; R3 represents -NHC(O)R10, -C(O)NR11R12 or -COOR12a; each radical among R4, R5, R6, R7 and R8 represents independently hydrogen atom (H) or (C1-C6)-alkyl; t = 0, 1 or 2; R9 represents halogen atom, -OH, -COOH, (C1-C6)-alkoxy group, (C1-C6)-alkoxycarbonyl; R10 represents group (C1-C6)-alkyl, (C3-C6)-cycloalkyl, or R10 represents -NR14R15; each R11 and R12 represents independently (1) H; (2) 3-6-membered saturated cycloalkyl or phenyl or 5-membered unsaturated heterocyclyl comprising from 1 to 4 heteroatoms N wherein indicated cycloalkyl, phenyl and heterocyclyl are substituted possibly with one or two substitutes chosen from -OH, (C1-C6)-alkyl, (C1-C6)-hydroxyalkyl; (3) (C1-C6)-alkyl substituted possibly at least with one substitute chosen from halogen atom, -OH, -COOH, (C1-C6)-alkylcarbonylamino group, phenyl, 5-membered unsaturated heterocyclyl comprising oxygen atom (O), or from 1 to 2 N atoms, bicycloheptyl wherein this phenyl, heterocyclyl or bicycloheptyl is substituted possibly at least with one substitute chosen from halogen atom, -OH, =O, or (4) (C1-C6)-alkylsulfonyl, or R11 and R12 in common with N atoms to which they are bound form 5-membered unsaturated heterocyclyl comprising one N atom or 5-6-membered heterocyclyl comprising from 1 to 2 heteroatoms, such as S, O and N, or 5-6-membered saturated heterocyclyl, ortho-condensed with benzene ring and comprising one N atom and wherein indicated heterocyclic systems are substituted possibly with one or two substitutes chosen from halogen atom, (C1-C6)-alkyl, (C1-C6)-hyroxyalkyl, (C1-C6)-halogenalkyl, (C1-C6)-alkylamino, di-(C1-C6)-alkylamino group, phenyl, halogenphenyl and hydroxydiphenylmethyl; R12a represents H or (C1-C6)-alkyl; each radical among R14 and R15 represents independently H or (C1-C6)-alkylsulfonyl, or R14 and R15 in common with N atom to which they are bound form 5-membered saturated heterocyclyl comprising one N atom and substituted possibly with one -OH, or its pharmaceutically acceptable salt or solvate. Also, invention relates to a method (variants) for synthesis of compound of the formula (I) according to one of the following method: by one variant, compound of the formula (II): is subjected for interaction with compound of the formula (III): by other variant, compound of the formula (IV): is subjected for interaction with compound of the formula (V): by other variant, compound of the formula (VI): wherein R3 represents -NHC(O)R10 and L1 represents a leaving group is subjected for interaction with L1C(O)R10; by other variant, compound of the formula (VIII): wherein R3 represents -C(O)NR11R12 and L2 represents a leaving group is subjected for interaction with compound of the formula (IX) given in the invention description. Also, invention relates to an intermediate compound of the formula (IIA): (wherein R1a is chosen from F, Cl, -CH3 and -CF3; s = 1 or 2; q = 0 or 1; w = 0 or 1; R2a represents F, and when q and s = 1 and w = 0 then R1a can't represent chlorine atom), and to a method for synthesis of compound of the formula (IIA) (wherein s = 1) and wherein compound of the formula (XX): is subjected for interaction with compound of the formula (XXII): (wherein R20 represent a protective group) before formation of compound of the formula (XXIV): followed by carrying out the cyclization reaction and removing the protective group R20.

EFFECT: improved methods of synthesis.

25 cl, 236 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to novel compounds of class quinoxalin-2-spiropyrroles of the general formula (I): wherein R1 = R2 mean hydrogen atom (H) (I); R1 means H; R2 means CH3 (II); R1 = R2 mean CH3 (III). Compound can be used as parent substances for synthesis of novel heterocyclic systems, and in medicine as antibacterial agents. Also, invention describes a method for synthesis of these compounds.

EFFECT: improved method of synthesis, valuable properties of compounds.

3 cl, 4 ex

FIELD: organic chemistry, medicine.

SUBSTANCE: invention describes novel spiroazacyclic compounds of the general formula: wherein X means -CH2, -CH2O, -OCH2 or oxygen atom (O); Y represents O; Z means -CH or nitrogen atom (N); R1 means (C1-C6)-alkyl optionally substituted with morpholinyl, 1,3-dioxanyl, 1,4-dioxanyl, 1,3-dioxolanyl, 2-oxoimidazolidinyl, imidazolidinyl, 2-oxooxazolidinyl, oxazalidinyl or (C3-C6)-cycloalkyl, (C2-C8)-alkyl ester or benzyl ester; m is chosen from group comprising 0 or 1; R4 means hydrogen atom or benzyl optionally substituted with halogen atom or (C1-C4)-alkyl; R5 means hydrogen atom or benzyl optionally substituted with halogen atom, (C1-C4)-alkyl or (C1-C4)-alkoxy-group; R6 means hydrogen atom or benzyl optionally substituted with (C1-C4)-alkoxy-, cycloalkyl-(C1-C4-alkoxy)- or halogen-(C1-C4-alkoxy)-group; R2 and R3 mean hydrogen atom and at least two radicals among R4, R5 and R6 mean optionally substituted benzyl. Also, invention relates to a method for inhibition of activity of serotonin 5-HT2A receptors, a method for treatment of state mediated by serotonin 5-HT2A receptors, and using spiroazacyclic compounds proposed.

EFFECT: improved method of treatment, valuable medicinal properties of compounds.

35 cl, 3 tbl, 2 dwg, 45 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compound of formula I: where: R1 represents R6C(O)-, R6SO2-, (R6)2NC(O)-; R2 represents hydrogen, -CF3 or R8; R3 represents -T-R9; R4 represents -COOH or -COOR8; R5 represents -CH2F or -CH2O-2, 3, 5, 6 - tetrafluorophenyl; R6 represents R6a or R6b; two R6 groups, together with the atom to which they are bound optionally form 3-10-member aromatic or non-aromatic ring; and where each R6 is independently substituted with 6 substituents, independently selected from R; R6a and R6b each independently represents (C1-C3)-aliphatic group, (C6-C10)-aryl-, (C6-C10)-aryl-(C1-C12) aliphatic group; R represents halogen, -OR7, -R7; each R7 is independently selected from: hydrogen, (C1-C12)-aliphatic group, (C6-C10)-aryl; R8 represents (C1-C12)-aliphatic group; T represents direct bond or (C1-C6)-aliphatic group, where to 2 aliphatic carbon atoms in T can be optionally substituted with O; R9 is optionally substituted (C6-C10)-aryl or (C5-C10) - heteroaryl, invention also relates to pharmaceutical composition, to methods of treatment, inhibition of caspase-mediated processes, to method of cell preservation with application of formula I compounds application of such compositions for treatment of caspase-mediated diseases and to methods of obtaining formula I compounds.

EFFECT: obtained and described are novel compounds, which can be useful in treatment of caspase-mediated diseases.

38 cl, 22 ex

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