1-(2-aminobenzol)piperazine derivatives as glycin uptake inhibitors to be used for psychosis treatment

FIELD: chemistry.

SUBSTANCE: there are disclosed 1-(2-aminobenzol)piperazine derivatives of formula (I) and pharmaceutically acceptable acid-additive salts with radical values specified in patent claim. The compounds are characterised with inhibiting effect on glycine I carrier. There is also disclosed medical product based on the compounds of formula (I).

EFFECT: compound can be used for treatment of the diseases associated with glycine uptake inhibition.

12 cl, 5 tbl, 396 ex

 

The text descriptions are given in facsimile form.

1. Derivatives of 1-(2-aminobenzoyl)piperazine of the formula:

where Ar represents a substituted phenyl or 6-membered heteroaryl containing one, two or three nitrogen atom, where the phenyl and heteroaryl groups are substituted with one to three substituents selected from the group consisting of halogen, NO2CN, (C1-C6)-alkyl, (C1-C6)-alkyl, substituted with halogen, (C1-C6)-alkoxy, (C1-C6)-alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
R1represents hydrogen or (C1-C6)-alkyl;
R2and R2'independently from each other represent Soboh is hydrogen, (CR2)nis hydroxy, in the case where R means hydrogen or (C1-C6)-alkyl, or represent (C1-C6)-alkyl, (C2-C6)-alkenyl, (CH2)n-(C3-C6-cycloalkyl, (CH2)n-heteroseksualci where heteroseksualci selected from tetrahydrofuranyl, tetrahydropyranyl, (CH2)n-O-(C1-C6)-alkyl or (CH2)n-phenyl, or
R2and R2'form together with the nitrogen atom to which they are attached, 4-7-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom selected from the group consisting of N, S or O, where these rings are unsubstituted or substituted by a group (CH2)nhydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, (CH2)n-O-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one, two or three additional nitrogen atom and where the heteroaryl group is optionally substituted (C1-C6)-alkyl;
R3, R4and R6independently of one another represent hydrogen, halogen;
R5represents NO2, CN, C(O)R9S-(C1-C6)-alkyl, SO2R10or is predstavljaet a NR 11R12;
R7and R8independently of one another represent hydrogen, (CH2)n-(C3-C6-cycloalkyl or (C1-C6)-alkyl, or form together with the nitrogen atom to which they are attached, 5-6-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom About;
R9is a (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8;
R10is a (C1-C6)-alkyl, (CH2)n-(C3-C6-cycloalkyl or NR7R8;
R11and R12independently of one another represent hydrogen, SO2-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one or three nitrogen atom, and where the heteroaryl group is optionally substituted (CH2)n(C3-C6-cycloalkyl;
n means 0, 1 or 2;
and pharmaceutically acceptable acid additive salt of this compound,
provided that the following compounds are excluded:
1-(4-methoxyphenyl)-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-(4-methoxyphenyl)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-(4-morpholinyl)-5-nitrobenzoyl]-4-[2-nitro-4-(trifluoromethyl)phenyl]piperazine, 1-(4-methoxyphenyl)-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-[2-[4-(2-hydroxyethyl)-1-piperazinil]-5-nitrobenzoyl]-4-(4-methoxyphenyl)piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-piperidinyl)-benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-pyrrolidinyl)-benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperidinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[5-[[methyl(phenylmethyl)amino]sulfonyl]-2-(4-morpholinyl)benzoyl]-4-(4-nitrophenyl)piperazine and
1-(4-acetyl-2-forfinal)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]-piperazine,
1-{4-[4-(2-morpholine-4-yl-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon.

2. Derivatives of 1-(2-aminobenzoyl)piperazine of the formula:

where Ar represents a substituted phenyl or 6-membered heteroaryl containing one, two or three nitrogen atom, and where the phenyl and heteroaryl groups are substituted with one to three substituents selected from the group consisting of halogen, NO2CN, (C1-C6)-alkyl, (C1-C6)-alkyl, substituted with halogen, (C1-C6)-alkoxy, (C1-C6)-alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
R 1represents hydrogen or (C1-C6)-alkyl;
R2and R2'independently of one another represent hydrogen, (C1-C6)-alkyl, (C3-C6)-alkenyl, (C3-C6-cycloalkyl, tetrahydropyranyl, tetrahydrofuranyl, (C1-C6)-alkyl-tetrahydropyranyl and (C1-C6)-alkyl-tetrahydrofuranyl, (C1-C6)-alkyl-(C3-C6-cycloalkyl, (C2-C6)-alkyl-O-R13, (C1-C6-alkylphenyl; or
R2and R2'form together with the nitrogen atom to which they are attached, 4-7-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom selected from the group consisting of N, S or O,
where these rings are unsubstituted or substituted by hydroxy group, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-alkyl-O-R13or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one, two other nitrogen atom and where the heteroaryl group is optionally substituted C1-C6)-alkyl or (C3-C6-cycloalkyl;
R3, R4and R6independently of one another represent hydrogen, halogen;
R5represents NO2, CN, C(O)R9 S-(C1-C6)-alkyl, SO2R10or represents NR11R12;
R7and R8independently of one another represent hydrogen, (C1-C6)-alkyl-(C3-C6-cycloalkyl or (C1-C6)-alkyl, or form together with the nitrogen atom to which they are attached, 5-6-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom About;
R9is a (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8;
R10is a (C1-C6)-alkyl, (C1-C6)-alkyl-(C3-C6-cycloalkyl or NR7R8;
R11and R12independently of one another represent hydrogen, SO2-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one or three other nitrogen atom, and where the heteroaryl group is optionally substituted (C3-C6-cycloalkyl;
R13represents hydrogen, (C1-C6)-alkyl;
and pharmaceutically acceptable acid additive salts of these compounds,
provided that the following compounds are excluded:
1-[2-[[2-(diethylamino)ethyl]amino]-5-nitrobenzoyl]-4-(methoxyphenyl)piperazine,
1-(4-methoxy who enyl)-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-(4-methoxyphenyl)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[2-(4-morpholinyl)-5-nitrobenzoyl]-4-[2-nitro-4-(trifluoromethyl)phenyl]piperazine,
1-(4-methoxyphenyl)-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-[2-[4-(2-hydroxyethyl)-1-piperazinil]-5-nitrobenzoyl]-4-(4-methoxyphenyl)piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-piperidinyl)benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[5-nitro-2-(1-pyrrolidinyl)benzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperidinyl)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-methyl-1-piperazinil)-5-nitrobenzoyl]piperazine,
1-[2-fluoro-4-(1-oxopropyl)phenyl]-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-[5-[[methyl(phenylmethyl)amino]sulfonyl]-2-(4-morpholinyl)benzoyl]-4-(4-nitrophenyl)piperazine and
1-(4-acetyl-2-forfinal)-4-[2-(4-morpholinyl)-5-nitrobenzoyl]piperazine,
1-{4-[4-(2-morpholine-4-yl-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon.

3. The compound of formula I-1 according to claim 1

where R' is a halogen, NO2CN, (C1-C6)-alkyl, (C1-C6)-alkyl, substituted with halogen, (C1-C6)-alkoxy, (C1-C6)-alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
m denotes 1, 2 or 3;
R1represents hydrogen or (C1-C6)-alkyl;
R2 and R 2'independently of one another represent hydrogen, (CR2)nis hydroxy, in the case where R means hydrogen or (C1-C6)-alkyl, or represent (C1-C6)-alkyl, (C2-C6)-alkenyl, (CH2)n-(C3-C6-cycloalkyl, (CH2)n-heteroseksualci where heteroseksualci selected from tetrahydrofuranyl, tetrahydropyranyl, (CH2)n-O-(C1-C6)-alkyl or (CH2)nis phenyl;
R3, R4and R6independently of one another represent hydrogen, halogen;
R5represents NO2, CN, C(O)R9S-(C1-C6)-alkyl, SO2R10or represents NR11R12;
R7and R8independently of one another represent hydrogen, (CH2)n-(C3-C6-cycloalkyl or (C1-C6)-alkyl, or form together with the nitrogen atom to which they are attached, 5-6-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom About;
R9is a (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8;
R10is a (C1-C6)-alkyl, (CH2)n-(C3-C6-cycloalkyl or NR7R8;
R11and R12independently of the other is from each other represent hydrogen, SO2-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one or three other nitrogen atom, and where the heteroaryl group is optionally substituted (CH2)n(C3-C6-cycloalkyl;
n means 0, 1 or 2;
and pharmaceutically acceptable acid additive salts of these compounds.

4. The compound of formula I-1 according to claim 3, which represents one of the following connections:
1-(4-{4-[2-(cyclopropylamino)-5-nitrobenzoyl]piperazine-1-yl}-3-forfinal)Etalon,
1-{4-[4-(2-cyclohexylamino-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon,
1-{4-[4-(2-diethylamino-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon,
1-{3-fluoro-4-[4-(2-isobutylamino-5-nitrobenzoyl)piperazine-1-yl]phenyl}Etalon,
1-{4-[4-(2-cyclobutylamine-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon,
1-{4-[4-(2-cyclobutylamine-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon,
1-{4-[4-(2-cyclopentylamine-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}alanon or
1-(4-{4-[2-(allylamino)-5-nitrobenzoyl]piperazine-1-yl}-3-forfinal)Etalon.

5. The compound of formula I-2 according to claim 1

where R' is a halogen, NO2CN, (C1-C6)-alkyl, (C1-C6)-alkyl, substituted with halogen, (C1-C6)-alkoxy, (C1 -C6)-alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
m denotes 1, 2 or 3;
R1represents hydrogen or (C1-C6)-alkyl;
is a 4-7-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom selected from the group consisting of N, S or O, where these rings are unsubstituted or substituted by a group (CH2)nhydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, (CH2)n-O-(C1-C6)-alkyl, or form together with the N atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one, two other nitrogen atom, and where the heteroaryl group is optionally substituted (C1-C6)-alkyl;
R3, R4and R6independently of one another represent hydrogen, halogen;
R5represents NO2, CN, C(O)R9S-(C1-C6)-alkyl, SO2R10or represents NR11R12;
R7and R8independently of one another represent hydrogen, (CH2)n-(C3-C6-cycloalkyl or (C1-C6)-alkyl, or form together with the nitrogen atom to which they are attached, 5-6-membered geteroseksualnoe to lzo, optionally containing in addition to the N atom one heteroatom About;
R9is a (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8;
R10is a (C1-C6)-alkyl, (CH2)n-(C3-C6-cycloalkyl or NR7R8;
R11and R12independently of one another represent hydrogen, SO2-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one or three other nitrogen atom, and where the heteroaryl group is optionally substituted (CH2)n(C3-C6-cycloalkyl;
n means 0, 1 or 2;
and pharmaceutically acceptable acid additive salts of these compounds.

6. The compound of formula 1-2 according to claim 5, which represents one of the following connections:
1-{3-fluoro-4-[4-(5-nitro-2-pyrrolidin-1-aventyl)piperazine-1-yl]phenyl}Etalon,
1-{3-fluoro-4-[4-(5-nitro-2-piperidine-1-aventyl)piperazine-1-yl]phenyl}Etalon,
1-{4-[4-(2-azepin-1-yl-5-nitrobenzoyl)piperazine-1-yl]-3-forfinal}Etalon,
1-(3-fluoro-4-{4-[2-(2-methylpiperidin-1-yl)-5-nitrobenzoyl]piperazine-1-yl}phenyl)Etalon,
1-(3-fluoro-4-{4-[2-(4-methylpiperidin-1-yl)-5-nitrobenzoyl]piperazine-1-yl}phenyl)Etalon,
1-(3-fluoro-4-{4-[2-(3-methylpiperidin-1-yl)-5-nitrobenzoyl]piperazine-1-yl}Fe is Il)Etalon,
1-(3-fluoro-4-{4-[2-(2-methylpyrrolidine-1-yl)-5-nitrobenzoyl]piperazine-1-yl}phenyl)Etalon,
1-(4-{4-[2-(2,5-dihydropyrrol-1-yl)-5-nitrobenzoyl] piperazine-1-yl}-3-forfinal)Etalon,
1-{3-fluoro-4-[4-(5-nitro-2-thiomorpholine-4-aventyl)piperazine-1-yl]phenyl}Etalon,
1-(3-fluoro-4-{4-[2-(3-hydroxypiperidine-1-yl)-5-nitrobenzoyl]piperazine-1-yl}phenyl)Etalon,
1-{4-[4-(2-azepin-1-yl-5-methansulfonate)piperazine-1-yl]-3-forfinal}Etalon,
1-{3-fluoro-4-[4-(5-methanesulfonyl-2-pyrrolidin-1-aventyl)piperazine-1-yl]phenyl}Etalon,
N-methyl-4-pyrrolidin-1-yl-3-[4-(4-triptoreline)piperazine-1-carbonyl]benzosulfimide,
N-methyl-4-morpholine-4-yl-3-[4-(4-triptoreline)piperazine-1-carbonyl]benzosulfimide,
3-[4-(4-acetyl-2-forfinal)piperazine-1-carbonyl]-N-methyl-4-pyrrolidin-1-albenzaalbenza,
1-(3-fluoro-4-{4-[2-(3-hydroxyethylpyrrolidine-1-yl)-5-nitrobenzoyl]piperazine-1-yl}phenyl)Etalon,
2-[4-(2-morpholine-4-yl-5-nitrobenzoyl)piperazine-1-yl]-5-cryptomathematical,
3-fluoro-4-[4-(5-methanesulfonyl-2-piperidine-1-aventyl)piperazine-1-yl]benzonitrile,
2-fluoro-4-[4-(5-methanesulfonyl-2-piperidine-1-aventyl)piperazine-1-yl]benzonitrile,
[4-(2-fluoro-4-triptoreline)piperazine-1-yl]-(5-methanesulfonyl-2-piperidine-1-ylphenyl)methanon,
[4-(3-fluoro-4-triptoreline)piperazine-1-yl]-(5-methanesulfonyl-2-piperidine-1-ylphenyl)methanon,
3-[4-(4-cyano-phenyl)piperazine-1-carbonyl]-N-methyl-4-pyrrolidin the-1-albenzaalbenza,
3-[4-(4-cyano-2-forfinal)piperazine-1-carbonyl]-N-methyl-4-pyrrolidin-1-albenzaalbenza,
3-[4-(2-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-pyrrolidin-1-albenzaalbenza,
3-[4-(3-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-pyrrolidin-1-albenzaalbenza,
3-[4-(4-acetyl-2-forfinal)piperazine-1-carbonyl]-N-methyl-4-piperidine-1-albenzaalbenza,
3-[4-(4-cyano-phenyl)piperazine-1-carbonyl]-N-methyl-4-piperidine-1-albenzaalbenza,
3-[4-(4-cyano-2-forfinal)piperazine-1-carbonyl]-N-methyl-4-piperidine-1-albenzaalbenza,
3-[4-(4-cyano-3-forfinal)piperazine-1-carbonyl]-N-methyl-4-piperidine-1-albenzaalbenza,
N-methyl-4-piperidine-1-yl-3-[4-(4-triptoreline)piperazine-1-carbonyl]benzosulfimide,
3-[4-(2-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-piperidine-1-albenzaalbenza,
3-[4-(2-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-piperidine-1-albenzaalbenza,
3-[4-(2-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-morpholine-4-albenzaalbenza or
3-[4-(3-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-morpholine-4-albenzaalbenza.

7. The compound of formula I-3 according to claim 1

where "hetaryl" represents a 6-membered heteroaryl containing one, two or three nitrogen atom, optionally substituted with one to three substituents, select nimi from the group consisting of halogen, NO2CN, (C1-C6)-alkyl, (C1-C6)-alkyl, substituted with halogen, (C1-C6)-alkoxy, (C1-C6)-alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
R1represents hydrogen or (C1-C6)-alkyl;
R2and R2'independently of one another represent hydrogen, (CR2)nis hydroxy, in the case where R means hydrogen or (C1-C6)-alkyl, or represent (C1-C6)-alkyl, (C2-C6)-alkenyl, (CH2)n-(C3-C6-cycloalkyl, (CH2)n-heteroseksualci where heteroseksualci selected from tetrahydrofuranyl, tetrahydropyranyl, (CH2)n-O-(C1-C6)-alkyl or (CH2)n-phenyl,
R3, R4and R6independently of one another represent hydrogen, halogen;
R5represents NO2, CN, C(O)R9S-(C1-C6)-alkyl, SO2R10or represents NR11R12;
R7and R8independently of one another represent hydrogen, (CH2)n-(C3-C6-cycloalkyl or (C1-C6)-alkyl, or form together with the nitrogen atom to which they are attached, 5-6-membered geteroseksualnoe ring, neobyazatelnostyu in addition to the N atom one heteroatom About;
R9is a (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8;
R10is a (C1-C6)-alkyl, (CH2)n-(C3-C6-cycloalkyl or NR7R8;
R11and R12independently of one another represent hydrogen, SO2-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one or three other
nitrogen atom, and where the heteroaryl group is optionally substituted (CH2)n(C3-C6-cycloalkyl;
n means 0, 1 or 2;
and pharmaceutically acceptable acid additive salts of these compounds.

8. The compound of formula I-4 according to claim 1

where "hetaryl" represents a 6-membered heteroaryl containing one, two or three nitrogen atom, optionally substituted with one to three substituents selected from the group consisting of halogen, NO2CN, (C1-C6)-alkyl, (C1-C6)-alkyl, substituted with halogen, (C1-C6)-alkoxy, (C1-C6)-alkoxy substituted by halogen, NR7R8C(O)R9or SO2R10;
R1represents hydrogen or (C1-C6)-alkyl;
is soboy-to 7-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom selected from the group consisting of N, S or O, where these rings are unsubstituted or substituted by a group (CH2)nhydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, (CH2)n-O-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one, two other nitrogen atom and where the heteroaryl group is optionally substituted (C1-C6)-alkyl;
R3, R4and R6independently of one another represent hydrogen, halogen;
R5represents NO2, CN, C(O)R9S-(C1-C6)-alkyl, SO2R10or represents NR11R12;
R7and R8independently of one another represent hydrogen, (CH2)n-(C3-C6-cycloalkyl or (C1-C6)-alkyl, or form together with the nitrogen atom to which they are attached, 5-6-membered geteroseksualnoe ring, optionally containing in addition to the N atom one heteroatom About;
R9is a (C1-C6)-alkyl, (C1-C6)-alkoxy or NR7R8;
R10is a (C1-C6)-alkyl, (CH2)n-(C3With 6-cycloalkyl or NR7R8;
R11and R12independently of one another represent hydrogen, SO2-(C1-C6)-alkyl, or form together with the nitrogen atom a 5-membered heteroaryl group, optionally containing in addition to the N atom one or three other nitrogen atom, and where the heteroaryl group is optionally substituted (CH2)n(C3-C6-cycloalkyl;
n means 0, 1 or 2;
and pharmaceutically acceptable acid additive salts of these compounds.

9. The compound of formula I-4 to clause 8, which represents one of the following connections:
3-[4-(3-fluoro-4-triptoreline)piperazine-1-carbonyl]-N-methyl-4-morpholine-4-albenzaalbenza,
(2-morpholine-4-yl-5-nitrophenyl)-[4-(5-triptorelin-2-yl)piperazine-1-yl]metano,
[4-(3-chloro-5-triptorelin-2-yl)piperazine-1-yl]-(2-morpholine-4-yl-5-nitrophenyl)methanon,
6-[4-(2-morpholine-4-yl-5-nitrobenzoyl)piperazine-1-yl]nicotinamide,
[4-(3-chloro-pyridine-2-yl)piperazine-1-yl]-(2-morpholine-4-yl-5-nitrophenyl)methanon,
(2-morpholine-4-yl-5-nitrophenyl)-[4-(4-triptorelin-2-yl)piperazine-1-yl]metano,
(2-morpholine-4-yl-5-nitrophenyl)-[4-(6-triptorelin-2-yl)piperazine-1-yl]metano,
[4-(5-bromo-pyrimidine-2-yl)piperazine-1-yl]-(2-morpholine-4-yl-5-nitrophenyl)methanon,
[4-(6-chloro-5-triptorelin-2-yl)piperazine-1-yl]-(2-morpholine-4-the l-5-nitrophenyl)methanon,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(2-cryptomaterial-4-yl)piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(6-cryptomaterial-4-yl)piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(5-cryptomaterial-2-yl)piperazine-1-yl]metano,
6-[4-(5-methanesulfonyl-2-morpholine-4-aventyl)piperazine-1-yl]nicotinamide,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(5-triptorelin-2-yl)piperazine-1-yl]metano,
[4-(3-chloro-5-triptorelin-2-yl)piperazine-1-yl]-(5-methanesulfonyl-2-morpholine-4-ylphenyl)methanon,
[4-(5-chloro-pyridine-2-yl)piperazine-1-yl]-(5-methanesulfonyl-2-morpholine-4-ylphenyl)methanon,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(6-triptorelin-3-yl)piperazine-1-yl]metano,
[4-(3-fluoro-5-triptorelin-2-yl)piperazine-1-yl]-(5-methanesulfonyl-2-morpholine-4-ylphenyl)methanon,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(6-methylpyridin-3-yl)-piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(5-methylpyridin-2-yl)-piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(4-triptorelin-2-yl)piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(6-triptorelin-2-yl)piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(2-trifluoromethyl-pyrimidine-5-yl)piperazine-1-yl]metano,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-[4-(6-Tr is formetal-pyridazin-3-yl)piperazine-1-yl]metano,
[4-(4-dimethylamino-[1,3,5]triazine-2-yl)piperazine-1-yl]-(5-methanesulfonyl-2-morpholine-4-ylphenyl)methanon or,
(5-methanesulfonyl-2-morpholine-4-ylphenyl)-(5'-trifluoromethyl-2,3,5,6-tetrahydro-[1,2']bipyridinyl-4-yl)methanon.

10. Drug, possess inhibitory activity against the glycine Transporter I (GlyT-1)containing one or more compounds according to claim 1 and pharmaceutically acceptable excipients.

11. The drug of claim 10 for the treatment of diseases based on the inhibition of the absorption of glycine.

12. The drug is one of PP-11, where the disease is a psychosis, pain, impairment of memory and ability to learn, schizophrenia, dementia and other diseases associated with cognitive processes such as attention deficit disorder, or Alzheimer's disease.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: described is novel compound of formula (I)

or its pharmaceutically acceptable salt, values of radicals are given in invention formula Compound has ability to inhibit receptor mGluR5, which intends it for prevention and/or treatment of receptor mGluR5- associated disturbances. Also described is pharmaceutical composition, method of inhibiting activation of receptors mGluR5, using compound of formula (I). Described is method of obtaining compound of formula 1a or 1b structure.

EFFECT: increasing output of suitable product.

18 cl, 825 ex

FIELD: chemistry.

SUBSTANCE: invention refers to benzothiazol derivatives of general formula (I) and to their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands and to based medicinal agent. In general formula (I) , R1 represents 1,4-dioxepanyl or tetrahydropyran-4-yl; R2 represents -N(R)-(CH2)n-5- or 6-merous nonaromatic heterocycle containing 1-2 nitrogen heteroatoms optionally substituted with one-two substitutes chosen from group, consisting of C1-C6alkyl or -NR2, or represents -(CH2)n-5- or 6-merous nonaromatic heterocycle containing 1-2 heteroatoms chosen of N, S or O, optionally substituted with group -(CH2)n-OH, C1-C6alkyl, C1-C6alkoxy, or represents -(CH2)n-5-or 6-merous aromatic heterocycle containing 1-2 nitrogen heteroatoms optionally substituted with the following group: C1-C6alkyl, C1-C6alkoxy, halogen, halogen-(C1-C6alkyl), -CH2N(R)(CH2)2OCH3, -N(R)(CH2)2OCH3, - CH2-morpholinyl or -CH2-pyrrolidinyl or represents (CH2)n-C3-C6cycloalkyl optionally substituted with group hydroxy, or represents -N(R)-C3-C6cycloalkyl optionally substituted with group hydroxy or C1-C6alkyl, or represents phenyl optionally substituted with group C1-C6alkoxy, halogen, halogen-(C1-C6alkyl), C1-C6alkyl, -CH2-pyrrolidine-1-yl, CH2N(R)(CH2)2OCH3 or -CH2-N(R)C(O)-(C1-C6alkyl), or represents 1,4-dioxa-8-azaspiro[4,5]decane, or 2-oxa-5-azabicyclo[2,2,1]heptane, or 1-oxa-8-azaspiro[4,5]decane, or -N(R)-7-oxabicyclo[2,2,1]hept-2-yl, or 2-azabicyclo[2,2,2]octane; R represents hydrogen or C1-C6alkyl; n stands for 0 or 1.

EFFECT: compounds can be applied for treatment and prevention of diseases mediated by adenosine A2A and A1 receptors, eg Alzheimer's disease, some depressions, toxicomania, Parkinson's disease.

8 cl, 3 dwg, 61 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: compounds of formula (I) as inhibitors of phosphotyrosine phosphotase 1B and their pharmaceutically acceptable salts, their application, based pharmaceutical composition and method of production. In general formula (I) , R1 indicates phenyl, naphthyl, thionaphthyl, pyridyl. Phenyl, naphthyl, thionaphthyl and pyridyl can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, (C1-C6)-alkyl, (C2-C6)-alkenyl, (C2-C6)-alkinyl, CF3, OCF3, N(R9)(R10), piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, NO2, CN, O-(C1-C6)-alkyl, S(O)0-2-(C1-C6)-alkyl, SO2-N(R9)(R10), CO-(C1-C6)-alkyl, -COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkyleny-COO(C1-C6)-alkyl, (C3-C10)-cycloalkyl, phenyl. These piperidinone, piperazine, piperazinone, N-(C1-C6-alkylene)-piperazine, N-(C1-C6-alkylene)-piperazinone, morpholine, thiomorpholine, and phenyl rings can be single- or multiple-substituted with F, Cl, Br, (CH2)0-2OH, COOH, CN, NO2, O-(C1-C6)-alkyl, -NH-O-(C1-C6)-alkyl, -(CO)-NH-O-(C1-C6)-alkylene-N(R9)(R10), -(CO)-(C1-C6)-alkyl, -(C1-C6)-alkyl, CF3, OCF3, N(R9)(R10); R2 indicates H, (C1-C6)-alkyl, COOH, (C1-C6)-alkylene-COOH, COO(C1-C6)-alkyl, (C1-C6)-alkylene-COO(C1-C6)-alkyl; R3 indicates H, (C1-C6)-alkyl, (C1-C6)-alkylenphenyl, -C(O)-phenyl, (C1-C6)-alkylenheterocycle, where heterocycle represents 5-6-merous heterocyclic ring containing 1-2 heteroatoms, chosen of nitrogen and oxygen, CO-(C1-C6)alkyl; R4, R5 indicate H; R6 indicates H, R9 indicates H, (C1-C4)-alkyl; R10 indicates H, (C1-C4)-alkyl.

EFFECT: applications for treating diseases mediated with phosphotyrosine phosphotase 1B activity, such as diabetes type II, lipidosis and carbohydrate metabolic imbalance, insulin resistivity, reduced sugar content in blood.

9 cl, 2 tbl, 1 ex

FIELD: chemistry; pharmacology.

SUBSTANCE: new compounds of formula (I) and its pharmaceutically acceptable salts. Offered compounds possess properties of bacterial gyrase and Topo-IV activity inhibitor. In general formula (I) , W is chosen from CH or CF; X represents CH; Z represents O or NH; R1 represents phenyl or 5-6-merous heteroaryl ring containing 1-3 nitrogen atoms where R1 is substituted with 0-3 groups independently chosen from -(T)y-Ar, R', oxo, C(O)R', OR', N(R')2, SR', CN or C(O)N(R')2; R2 is chosen from C1-3alkyl and C3-7-cycloalkyl; and ring A represents 5-6-merous heteroaryl ring containing 1-3 heteroatoms, independently chosen of nitrogen, oxygen or sulphur provided the specified ring has hydrogen bond acceptor in position adjacent to that of joining to B ring where ring A is substituted with 0-3 groups independently chosen from R', oxo, CO2R', OR', N(R')2, halogen, CN, C(O)N(R')2, NR'C(O)R', or NR'SO2R', and where two substitutes in adjacent positions of ring A, together can form 6-merous saturated heterocyclic or heteroaryl ring containing 1-2 nitrogen atoms.

EFFECT: pharmaceutical compositions with properties of bacterial gyrase and Topo-IV activity inhibitor containing disclosed compound as active component, method of gyrase and/or Toro IV-activity inhibition, method of bacteria number reduction.

25 cl, 3 tbl, 4 dwg, 29 ex

FIELD: medicine.

SUBSTANCE: formula bond

or it pharmaceutically comprehensible salt where value of radicals are specified in the invention formula is described. The bonds are effective as inhibitors of protein kinases FLT-3 or KIT. A way of inhibition of activity kinases FLT-3 or KIT in the biological sample in vitro and application of bonds for manufacture of a medical product, suitable for treatment or simplification of gravity of disease or a condition, the chosen acute myelogenetic leukosis, acute progranulocytic leukemia or acute lymphocytic leukosis or cancer of ovaries are described also.

EFFECT: rising of efficiency of a composition and the method of treatment.

11 cl, 86 ex

FIELD: medicine.

SUBSTANCE: invention offers analogues of quinazoline of the formula I

where A is bound at least with one of atoms of carbon in position 6 or 7 of the dicyclic ring; X represents N. A represents the group Q or Z including tautomeric group Z form where Q and Z, have the formulas resulted more low in which symbols and radicals, have the value specified in item 1 of the formula of the invention. R1 represents phenyl, substituted -(G)nOAr or -O(G)nAr and where phenyl is unessentially replaced by halogen or C1-C10alkyl; where G represents C1-C4alkylene, n is peer 0 or 1. And Ar represents phenyl either pyridyl or thiazolyl where Ar is unessentially substituted by 1-2 substituents chosen from halogen or C1-C10alkyl; R2 and R3 represent N. The bonds of the formula I are inhibitors of the receptor tyrosine kinases of type 1. The invention includes also a way of treatment of hyperproliferative diseases, such as a cancer, application of bonds of the formula 1 in manufacture of medical products and pharmaceutical composition on the basis of these bonds.

EFFECT: rising of efficiency of a composition and the method of treatment.

14 cl, 6 dwg, 63 ex

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: chemistry.

SUBSTANCE: invention concerns new compounds of the formula (I) and their pharmaceutically acceptable salts. Claimed compounds have antibacterial effect. In formula (I) , X is ; R1 is i) hydrogen, ii) (CH2)nNR5R6, iv) NRCO2R, v) (C1-6alkyl)CN, CN, (CH2)pOH; Y is NR*, O or S(O)p; is phenyl or 5-6-member heteroaryl with N or S as heteroatoms; R3 is NR(C=X2)R12, NR*R12, or -(O)n-5-6-member heteroaryl with 1-3 heteroatoms selected out of N, O, which can be linked over either carbon atom or heteroatom; the indicated 5-6-member heteroaryl can be optionally substituted by 1-3 groups of R7; R4, R4a, R4b and R4c are independently i) hydrogen, ii) halogen; other radicals are defined in the claim.

EFFECT: pharmaceutical composition containing effective volume of the claimed compound.

13 cl, 1 dwg, 194 ex

FIELD: chemistry.

SUBSTANCE: invention concerns benzothiazole derivatives of general formula (1) and their pharmaceutically acceptable acid-additive salts as adenosine receptor ligands with high affinity to A2A adenosine receptor, and based medicine. Compounds can be applied in treatment and prevention of diseases mediated by A2A adenosine receptors, such as Alzheimer's disease, some depressive states, toxicomania, Parkinson's disease. In general formula (I) , R is C5-C6-cycloalkyl non-substituted or substituted by hydroxy group, or is ethyl or isobutyl, or is tetrahydropyrane-4-yl or -(CH2)n-tetrahydrofurane-2 or 3-yl or is 5-hydroxybicyclo[2,2,1]hept-2-yl; X is CH or N; n is 0 or 1.

EFFECT: enhanced efficiency of composition and treatment method.

12 cl, 2 dwg, 14 ex

FIELD: chemistry.

SUBSTANCE: invention concerns method of treatment, alleviation and/or prevention of neurological state, particularly neurodegenerative disorders, involving administration of effective quantity of compound with formula I: . Also invention concerns application of compound of the formula I as neurotherapeutical, neuroprotective or antimyloid agent, pharmaceutical or veterinary composition for treatment, alleviation and/or prevention of neurological states, and compounds of the formula I on the following additional terms: (b) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not ethyl or methyl; (c) if R3, R and R' are H, and R2 is (CH2)2NR9R10, then both R9 and R10 are not hydrogen or ethyl; (d) if R3, R and R' are H, and R2 is NR11R12, then both R11 and R12 are not hydrogen; (e) if R3, R and R' are H, and R2 is COR6, then R6 is not H, OH or CH2Cl; (f) if R3, R and R' are H, and R2 is not CH3 or CH2Cl; (g) if R3, R and R' are H, and R2 is HCNN R9R10, then both R9 and R10 are not H.

EFFECT: efficient treatment, alleviation and prevention of neurological state.

24 cl, 14 tbl, 21 ex, 14 dwg

FIELD: organic chemistry, medicine.

SUBSTANCE: invention relates to compound of the formula (I): wherein R1 represents azido, -OR4, -NHR4 wherein R4 represents hydrogen atom or unsubstituted groups chosen from acyl, thioacyl, (C1-C6)-alkoxycarbonyl, (C3-C6)-cycloalkoxythiocarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy, -C(C=S)-S-(C1-C6)-alkyl, -(C=S)-NH2, -(C=S)-NH-(C1-C6)-alkyl, -C(=S)-N-((C1-C6)-alkyl)2, -C(=S)-NH-(C2-C6)-alkenyl, -C(C=S)-(C=O)-(C1-C6)-alkoxy, thiomorpholinylthiocarbonyl; R2 and R3 can be similar or different and represent independently hydrogen atom, halogen atom, (C1-C6)-alkyl group, halogen-(C1-C6)-alkyl; heterocyclic moiety represents 5-membered heterocycle wherein Z represents sulfur (S), oxygen (O) atom or -NRb wherein Rb represents hydrogen atom or unsubstituted (C1-C6)-alkyl, (C3-C6)-cycloalkyl, aryl or aryl-(C1-C6)-alkyl; Y1 represents group =O or =S ; Y2 and Y3 represent independently hydrogen atom, and if Y2 and Y3 present in common on adjacent carbon atoms then they form 6-membered aromatic cyclic structure substituted if necessary with (C1-C6)-alkyl, or to its pharmaceutically acceptable salt. Also invention relates to a pharmaceutical composition possessing antibacterial activity and containing as an active compound the compound of the formula (I) taken in the effective dose and a pharmaceutically acceptable carrier, diluting agent, excipient. Also, invention relates to method for synthesis of compound of the formula (I). Method for synthesis of compound of the formula (I) wherein R1 represents group -NHR4 wherein R4 means acyl, (C1-C6)-alkoxycarbonyl, (C2-C6)-alkenyloxycarbonyl, (C2-C6)-alkenylcarbonyl, -C(=O)-C(=O)-(C1-C6)-alkoxy and -(C=S)-S-(C1-C6)-alkyl involves acetylation of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 represents hydrogen atom and all symbols are given above and using halide. Method for synthesis of compound of the formula (I) wherein R1 represents -NHR4 group wherein R4 means thioacyl, (C3-C6)-cycloalkoxythiocarbonyl, (C1-C6)-alkoxythiocarbonyl, (C2-C6)-alkenyloxythiocarbonyl involves the following steps: (i) conversion of compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents hydrogen atom, and all symbols are given above to compound of the formula (I) wherein R1 represents isothiocyanate group by reaction with thiophosgene, and (ii) conversion of compound of the formula (I) wherein R1 represents isothiocyanate group to compound of the formula (I) wherein R1 represents -NHR4 wherein R4 represents -C(=S)-OR4d wherein R4d represents (C1-C6)-alkyl, (C3-C6)-cycloalkyl, (C2-C6)-alkenyl, and all symbols are given above, in reaction with alcohol. Compounds of the formula (I) are used in treatment of bacterial infection that involves administration of compound of the formula (I) in a patient needing in this treatment. Invention provides synthesis of oxazolidinone compounds possessing antibacterial activity.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition, improved method of synthesis.

7 cl, 1 tbl, 144 ex

FIELD: organic chemistry, medicine, endocrinology.

SUBSTANCE: invention relates to novel compounds representing C-glycoside derivatives and their salts of the formula: wherein ring A represents (1) benzene ring; (2) five- or six-membered monocyclic heteroaryl ring comprising 1, 2 or 4 heteroatoms chosen from nitrogen (N) and sulfur (S) atoms but with exception of tetrazoles, or (3) unsaturated nine-membered bicyclic heterocycle comprising 1 heteroatom representing oxygen atom (O); ring B represents (1) unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (2) saturated or unsaturated five- or six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O; (3) unsaturated nine-membered bicyclic carbocycle, or (4) benzene ring; X represents a bond or lower alkylene wherein values for ring A, ring B and X correlate so manner that (1) when ring A represents benzene ring then ring B is not benzene ring, or (2) when ring A represents benzene ring and ring B represents unsaturated eight-nine-membered bicyclic heterocycle comprising 1 or 2 heteroatoms chosen from N, S and O and comprising benzene ring or unsaturated nine-membered bicyclic carbocycle comprising benzene ring then X is bound to ring B in moiety distinct from benzene ring comprised in ring B; each among R1-R4 represents separately hydrogen atom, -C(=O)-lower alkyl or lower alkylene-aryl; each R5-R11 represents separately hydrogen atom, lower alkyl, halogen atom, -OH, =O, -NH2, halogen-substituted lower alkyl-sulfonyl, phenyl, saturated six-membered monocyclic heterocycle comprising 1 or 2 heteroatoms chosen from N and O, lower alkylene-OH, lower alkyl, -COOH, -CN, -C(=O)-O-lower alkyl, -O-lower alkyl, -O-cycloalkyl, -O-lower alkylene-OH, -O-lower alkylene-O-lower alkyl, -O-lower alkylene-COOH, -O-lower alkylene-C(=O)-O-lower alkyl, -O-lower alkylene-C(=O)-NH2, -O-lower alkylene-C(=O)-N-(lower alkyl)2, -O-lower alkylene-CH(OH)-CH2(OH), -O-lower alkylene-NH, -O-lower alkylene-NH-lower alkyl, -O-lower alkylene-N-(lower alkyl)2, -O-lower alkylene-NH-C(=O)-lower alkyl, -NH-lower alkyl, -N-(lower alkyl)2, -NH-lower alkylene-OH or NH-C(=O)-lower alkyl. Indicated derivatives can be used as inhibitor of co-transporter of Na+-glucose and especially as a therapeutic and/or prophylactic agent in diabetes mellitus, such as insulin-dependent diabetes mellitus (diabetes mellitus 1 type) and non-insulin-dependent diabetes mellitus (diabetes mellitus 2 type), and in diseases associated with diabetes mellitus, such as insulin-resistant diseases and obesity.

EFFECT: valuable medicinal properties of compounds.

11 cl, 41 tbl, 243 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel substituted derivatives of 4-phenyltetrahydroisoquinoline of the general formula (I): wherein R1, R2, R3 and R4 mean independently of one another hydrogen (H), fluorine (F), chloride (Cl), bromine (Br) atoms, CaH2a+1 wherein one or more atoms H are substituted with F, -NR11R12 or -SOj-R15 wherein a = 1-8; R11 and R12 mean independently of one another H, CeH2e+1 or CrrH2rr-1 wherein e = 1-4; rr = 3, 4, or in common with nitrogen atom to which they are bound form a cycle chosen from group consisting of pyrrolidinyl, piperidinyl, N-methylpiperazinyl, piperazinyl or morpholine; j = 1 or 2; R15 means CkH2k+1 wherein k = 1-8; R5 means CpH2p+1 or CssH2ss-1; p = 1-8; ss = 3-8; R6 means H; R7, R8 and R9 mean independently of one another mean -SOwR23, -NR32COR30, NR32CSR30, -NR32SObbR30, H, F, Cl, Br, -OH, -NH2, CeeH2ee+1, -NR40R41, -CONR40R41 or -COOR42 wherein w = 0, 1 or 2; bb = 2 or 3; R23 means NR25R26 wherein R25 and R26 mean independently of one another H or CzH2z+1, CzzH2zz-1 wherein z = 1-8; zz = 3-8 wherein in CzH2z+1 and CzzH2zz-1 one or more H atoms are substituted with fluorine atom and one or more CH2-groups are substituted with -C(=O) or NR27 wherein R27 means H or CaaH2aa+1 wherein aa = 1-4; or R25 and R26 in common with nitrogen atom to which they are bound form 5-, 6- or 7-membered cycle; R30 means H, CccH2cc+1, CyyH2yy-1, pyrrolydinyl, piperidinyl wherein in their cycles CH2-group can be substituted with oxygen atom (O) or -NR33; R32 and R33 mean independently of one another H or ChH2h+1 wherein cc = 1-8; yy = 3-8; h = 1-8 wherein in the group ChH2h+1 one or more hydrogen atoms are substituted with fluorine atom, and in the groups CccH2cc+1 and CyyH2yy-1 one or more hydrogen atoms can be substituted with fluorine atom, and CH2-group can be substituted with O or -NR31 wherein NR31 means H, methyl, ethyl, acetyl or -SO2CH3; or R30 means 6-membered heteroaryl with 1-4 nitrogen atoms, 0 or 1, S-atoms or 0, or 1 O-atom that represents unsubstituted or substituted with up to three substitutes chosen from group consisting of F, Cl, Br, J, CooH2oo+1 wherein one or more hydrogen atoms can be substituted with fluorine atom, -NO2 or -NR70R71 wherein oo = 1-8; R70 and R71 mean independently of one another H, CuuH2uu+1 or -COR72 wherein uu = 1-8; R72 means H, CvvH2vv+1 wherein vv = 1-8; ee = 1-8; R40 and R41 mean independently of one another H, CttH2tt+1 or -C(NH)NH2 wherein tt = 1-8 and wherein in the group CttH2tt+1 one or more CH2-groups can be substituted with NR44 wherein R44 means CggH2gg+1 wherein gg = 1-8; R42 means H or ChhH2hh+1 wherein hh = 1-8 being, however, two substitutes from group R7, R8 and R9 can't mean -OH simultaneously, and at least one residue from R7, R8 and R9 must be chosen from group consisting of -CONR40R41, -OvSOwR23, -NR32COR30, -NR32CSR30 and -NR32SObbR30. Also, invention relates to using above given compounds for preparing a medicinal agent. Also, invention considers a medicinal agent representing inhibitor of sodium-proton exchange of subtype III (NHE3) based on proposed compounds. Invention provides synthesis of novel compounds, a medicinal agent based on thereof for aims of treatment of such diseases as nervous system ischemia, insult and brain edema, in treatment of snore, shock, impaired respiratory impulse, as purgative agents, as agents against extoparasites, for prophylaxis of gall stones formation, as anti-atherosclerotic agents, agents against diabetes mellitus later complications, cancer diseases, fibrous diseases, endothelial dysfunction, hypertrophies and hyperplasia of organs and others.

EFFECT: valuable medicinal properties of compounds and medicinal agents.

21 cl, 15 tbl, 221 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to derivative compound of carboxylic acid represented by the formula (I): , wherein each X and Y represents independently (C1-C4)-alkylene; Z means -O-; each R1, R2, R3 and R4 means independently hydrogen atom or (C1-C8)-alkyl; R5 means (C2-C8)-alkenyl; A means -O- or -S-; D means D1, D2, D3, D4 or D5 wherein D1 means (C1-C8)-alkyl; D2 means compound of the formula: wherein ring 1 represents saturated 6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom chosen from oxygen, sulfur and nitrogen atoms; D3 means compound of the formula: wherein ring 2 represents (1) completely saturated (C3-C10)-monocarboxylic aryl, or (2) optionally saturated 5-membered monoheteroaryl comprising 3 atoms chosen from nitrogen and sulfur atoms, or completely saturated 6-membered monoheteroaryl comprising 1 heteroatom representing oxygen atom; D4 means compound of the formula: ; D5 means compound of the formula: ; R6 represents (1) hydrogen atom, (2) (C1-C8)-alkyl, (3) -NR7R8 wherein R7 or R8 represent hydrogen atom or (C1-C8)-alkyl, or R7 and R8 taken in common with nitrogen atom to which they are added form saturated 5-6-membered monoheteroaryl comprising one nitrogen atom and, optionally, another one heteroatom representing oxygen atom; E means -CH or nitrogen atom; m means a whole number 1-3, or its nontoxic salt. Invention relates to a regulator activated by peroxisome proliferator receptor, agent used in prophylaxis and/or treatment of diseases associated with metabolism disorders, such as diabetes mellitus, obesity, syndrome X, hypercholesterolemia or hyperlipoproteinemia, hyperlipidemia, atherosclerosis, hypertension, diseases coursing with circulation disorder, overeating or heart ischemic disease, and to an agent that increases cholesterol level associated with HDL, reduces cholesterol level associated with LDL and/or VLDL, eliminates risk factor in development of diabetes mellitus and/or syndrome X and comprising a compound represented by the formula (I) or its nontoxic salt as an active component and a carrier, excipient or solvent optionally. Invention proposes derivative compounds of carboxylic acid possessing the modulating activity with respect to peroxisome proliferator receptor (PPAR).

EFFECT: valuable medicinal properties of compounds.

15 cl, 5 tbl, 48 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of compound of the formula (1): wherein Y means -O-, -S- or -N(R2)- wherein R2 means hydrogen atom, (C1-C10)-alkyl or aralkyl; Z means 2,5-furanyl, 2,5-thiophenyl, 4,4'-stilbenyl or 1,2-ethyleneyl residue; R1 means hydrogen or halogen atom, (C1-C10)-alkyl, (C1-C10)-alkoxy-group, cyano-group, -COOM or -SO3M wherein M means hydrogen atom or alkaline or alkaline-earth metal atom. Method for synthesis involves carrying out the reaction of compound of the formula (2): with dicarboxylic acid of the formula: HOOC-Z-COOH (3) or with it ester wherein Y, Z and R1 have values given above in N-methylpyrrolidone or N,N-dimethylacetamide medium in the presence of an acid catalyst and optionally in the presence of an accessory solvent able to remove water from the reaction mixture.

EFFECT: improved method of synthesis.

11 cl, 7 ex

FIELD: organic chemistry, technology of organic compounds.

SUBSTANCE: invention relates to heterocyclic o-dicarbonitriles. Invention describes heterocyclic o-dicarbonitriles of the general formula: wherein R means the following compounds: . Heterocyclic o-dicarbonitriles can be used for preparing hexazocyclanes-fluorophores as a donor-fragment used for preparing hexazocyclanes-bifluorophores and hexazocyclanes-trifluorophores. Invention provides preparing new compounds possessing valuable properties.

EFFECT: valuable properties of compounds.

2 tbl, 10 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to new biologically active derivatives of dihydrobenzo[b][1,4]diazepine-2-one. Invention describes derivatives of dihydrobenzo[b][1,4]diazepine-2-one of the general formula (I): wherein X means a simple bond or ethynediyl group wherein if X means a simple bond then R1 means cyano-group, halogen atom, lower alkyl, (C1-C3)-cycloalkyl, (lower)-alkoxyl, fluoro-(lower)-alkyl or it means pyrrole-1-yl that may be free or substituted with 1-3 substitutes taken among the group consisting of fluorine, chlorine atom, cyano-group, -(CH2)1-4-hydroxyl group, fluoro-(lower)-alkyl, lower alkyl, -(CH2)n-(lower)-alkoxyl, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'', hydroxy-(lower)-alkoxyl and -(CH2)n-COR'R'', or it means free phenyl or phenyl substituted with one or two substitutes taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, fluoro-(lower)-alkoxyl and cyano-group; if X means ethynediyl group then R1 means free phenyl or phenyl substituted with 1-3 substituted taken among the group consisting of halogen atom, lower alkyl, fluoro-(lower)-alkyl, (C3-C6)-cycloalkyl, (lower)-alkoxyl and fluoro-(lower)-alkoxyl; R2 means -NR'R'', fluoro-(lower)-alkoxyl or 3-oxopiperazin-1-yl, pyrrolidin-1-yl, or piperidin-1-yl wherein their rings are substituted optionally with R''; R' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl or 2-(lower)-alkoxy-(lower)-alkyl; R'' means hydrogen atom, lower alkyl, (C3-C6)-cycloalkyl, fluoro-(lower)-alkyl, 2-(lower)-alkoxy-(lower)-alkyl, -(CH2)2-4-di-(lower)-alkylamino-group, -(CH2)2-4-morpholinyl, -(CH2)2-4-pyrrolidinyl, -(CH2)2-4-piperidinyl or 3-hydroxy-(lower)-alkyl; Y means -CH= or =N-; R3 means halogen atom, lower alkyl, fluoro-(lower)-alkyl, (lower)-alkoxyl, cyano-group, -(CH2)n-C(O)OR'', -(CH2)1-4-NR'R'' or it means optionally substituted 5-membered aromatic heterocycle that can be substituted with halogen atom, fluoro-(lower)-alkyl, fluoro-(lower)-alkoxyl, cyano-group, -(CH2)n-NR'R'', -(CH2)n-C(O)OR'', -(CH2)n-C(O)NR'R'', -(CH2)n-SO2NR'R'', -(CH2)n-C(NH2)=NR'', hydroxyl, (lower)-alkoxyl, (lower)-alkylthio-group or lower alkyl that is optionally substituted with fluorine atom, hydroxyl, (lower)-alkoxyl, cyano-group or carbamoyloxy-group; n means 0, 1, 2, 3 or 4, and their pharmaceutically acceptable additive salts. Also, invention describes a medicinal agent as antagonist of mGlu receptors of group II based on compounds of the formula (I). Invention provides preparing new compounds eliciting valuable biological properties.

EFFECT: valuable medicinal properties of compounds.

17 cl, 496 ex

The invention relates to novel polycyclic to dihydrothiazolo General formula (I), where Y is a simple bond; X is CH2; R1 is H, F, Cl, NO2, CN, COOH, (C1-C6)-alkyl, (C2-C6)-quinil, O-(C1-C6)-alkyl, and alkyl residues one, several or all of the hydrogen atoms may be replaced by fluorine; (CH2)n-phenyl, SO2-(C1-C6)-alkyl, and n = 0 and the phenyl residue up to twice may be substituted by F, Cl, CF3, OCF3, O-(C1-C6)-alkyl, (C1-C6)-alkyl; O-(CH2)n-phenyl, and n = 0 and phenyl cycle can be one - to twofold substituted by Cl, (C1-C6)-alkyl; 1 - or 2-naphthyl, 2 - or 3-thienyl; R1' is hydrogen; R2 is H, (C1-C6)-alkyl, R3 is hydrogen; R4 - (C1-C8)-alkyl, (C3-C7-cycloalkyl, (CH2)n-aryl, and n = 0-1, and aryl can be phenyl, 2-, 3 - or 4-pyridyl, 2 - or 3-thienyl, 2 - or 3-furyl, indol-3-yl, indol-5-yl, and aryl or heteroaryl residue up to twice may be substituted by F, Cl, HE, OCF3, O-(C1-C6)-alkyl, (C1-C6)-alkyl, 2-, 3-, 4-pyridium, pyrrol-1-yl, with peregrinae ring may be substituted CF3; and their physio is

FIELD: chemistry.

SUBSTANCE: invention relates to tetrahydrochinoline derivatives represented by general formula , where t is equal 0, 1 or 2; each R independently represents H, alkyl, alkenyl or cycloalkyl; n is equal 0; R is selected from group, consisting of H, alkyl, halogenalkyl, cycloalkyl, alkenyl, alkinyl, -RaAy, -RaOR5 or group - Racycloalkyl, and where R2 is not substituted with amine or alkylamine; each R4 independently represents halogen; m is equal 0, 1 or 2; each R5 independently represents H, alkyl, alkenyl, alkinyl, cycloalkyl; p is equal 0 or 1; y represents -NR10-, -O-, -S-; X represents -N(R10)2, -RaN(R10)2, -AyN(R10)2, -RaAyN(R10)2, -AyRaN(R10)2, -RaAyRaN(R10)2, -Het, -RaHet, -HetN(R10)2, -RaHetN(R10)2, -HetRaN(R10)2, -RaHetRaN(R10)2, -HetRaAy or -HetRaHet; each Ra independently represents alkylene, possibly suibstituted with one or more than one alkyl or hydroxyl, cycloalkylene, possibly substituted with one or more than one alkyl or hydroxyl; each R10 independently represents H, alkyl, cycloalkyl, alkenyl, alkinyl, cycloalkenyl or -Ra-cycloalkyl; each Ay independently represents possibly substituted phenyl or naphtyl group; each Het independently represents possibly substituted 3-12-member mono- or polycyclic heterocyclyl group, containing as heteroatoms N, or 5-7-member possibly substituted heteroaryl group, containing as heteroatom N; or its pharmaceutically acceptable salts or ethers. Also described are methods of obtaining compounds of formula (I-G).

EFFECT: obtained are novel compounds, which demonstrate protective against HIV-infection effect on target-cells by means of specific binding with chemokine receptor and which influence binding of natural ligand or chemokine with target-cell receptor, such as CXCR4 and/or CCR5.

54 cl, 2 tbl, 90 ex

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