Production and application of arylalkyl derivative acids for obesity treatment

FIELD: chemistry.

SUBSTANCE: invention refers to new compounds of formula (I) and its pharmaceutically acceptable salts and esters. Compounds of the present invention are characterised with properties of DGAT-1 inhibitor. In general formula (I) , Q represents O, S or NR5; A represents a linker chosen from where p is equal to 1 or 2, and , where m is equal to 0, and n is equal to 1, 2, 3 or 4, or m is equal to 1, while n is equal to 1, 2 or 3, where specified linker is optionally substituted with one or two groups R8; R1 and R2 are independently chosen from hydrogen, haloid; R3 is chosen from hydrogen, (C1-C6)alkyl optionally substituted with hydroxyl and phenyl optionally substituted with haloid; R4 is chosen from hydrogen, nitro and (C1-C6)alkyl; or R3 and R4 together with carbon atoms whereto attached, can form benzene ring optionally substituted with 1-2 substitutes. The invention also concerns compounds of formula (Ia) and (Ib) with structural formulas presented in the patent claim, and also to a pharmaceutical composition, a medical product, to application of compounds for making a medical product and compound process.

EFFECT: new compounds possess useful biological activity.

19 cl, 2 tbl, 7 dwg, 215 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where Q represents O, S or NR5;
Rather it represents a linker selected from
,
where p is 1 or 2
and
,
where m is 0 and n is 1, 2, 3,or 4
or
m is 1 and n is 1, 2 or 3,
where the specified linker optionally substituted with one or two groups R8;
R1and R2independently selected from in the of aroda, halogen;
R3choose from
hydrogen
(C1-C6)alkyl, optionally substituted by hydroxyl,
and
phenyl, optionally substituted by halogen;
R4selected from hydrogen, nitro, and (C1-C6)alkyl;
or
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]aminocarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)alkylsulfonyl, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl, and
when these two substituent of the benzene ring represent a (C1-C6)alkyl and is attached to adjacent carbon atoms of the benzene ring, they may be joined together with formation of a 5-7-membered saturated carbocyclic ring;
R5represents hydrogen or (C1-C6)alkyl;
R6represents hydrogen;
R7is a (C1-C )alkyl, optionally substituted
(C1-C6)alkoxy,
bis[(C1-C3)alkyl]amino
or
by phenyl;
or
R6and R7both are (C1-C6)alkyl;
or
R6and R7together with the carbon atom to which they are attached, may form a 3-5 membered carbocyclic ring
or
6-membered ring, represented as

where W represents CH2Oh , NR9, S or SO2;
R8is a (C1-C6)alkyl;
and
R9is a (C1-C6)alkyl;
or its pharmaceutically acceptable salts and esters.

2. The compound according to claim 1,
where Q represents NR5;
But a
,
where p is 1 or 2
where the specified linker optionally substituted with one or two groups R8;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]AMI is carbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)alkylsulfonyl, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl, and
R1R2, R5, R6, R7, R8, R9and W such as specified in claim 1.

3. The compound according to claim 1,
where Q represents NR5;
But a
,
where m is 0 and n is 1, 2, 3,or 4
or
m is 1 and n is 1, 2 or 3,
where the specified linker optionally substituted with one or two groups R8;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]aminocarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)alkylsulfonyl, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl, and
R1, R2, R5and R8such as specified in claim 1.

4. The compound according to claim 1,
where Q p is ecstasy themselves;
But a
,
where p is 1 or 2
where the specified linker optionally substituted with one or two groups R8;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]aminocarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)alkylsulfonyl, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl, and
R1R2, R6, R7, R8, R9and W such as specified in claim 1.

5. The compound according to claim 1,
where Q represents O;
But a
,
where m is 0 and n is 1, 2, 3,or 4
or
m is 1 and n is 1, 2 or 3,
where the specified linker optionally substituted with one or two groups R8;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted by substituent and up to two selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C6-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]aminocarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)alkylsulfonyl, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl,
and
R1, R2and R8such as specified in claim 1.

6. The compound according to claim 1,
where Q represents S;
But a
,
where p is 1 or 2,
where the specified linker optionally substituted with one or two groups R8;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]aminocarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)and is killalpaninna, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl, and
R1, R2, R6, R7, R8, R9and W such as specified in claim 1.

7. The compound according to claim 1,
where Q represents S;
But a
,
where m is 0 and n is 1, 2, 3,or 4
or
m is 1 and n is 1, 2 or 3,
where the specified linker optionally substituted with one or two groups R8;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, nitro, cyano, (C1-C6)haloalkyl, (C1-C6)haloalkoxy, (C1-C6)alkylsulfonyl, (C1-C6)alkylaminocarbonyl, bis[(C1-C6)alkyl]aminocarbonyl, (C1-C6)alkylaminocarbonyl, (C1-C6)alkylcarboxylic, (C1-C6)alkylsulfonyl, hydroxy-(C2-C6)alkylaminocarbonyl and 1-morpholinylcarbonyl, and
R1, R2and R8such as specified in claim 1.

8. The compound according to claim 1, selected from the group consisting of:
4-[4'-(1H-benzimidazole-2-ylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid;
4-{4'-[(5-methoxy-1H-benzimidazole-2-yl)amine is]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
TRANS-2-{[4'-(1H-benzimidazole-2-ylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5-methoxy-1H-benzimidazole-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)picopeta-carboxylic acid;
TRANS-2-[(4'-{[5-(trifluoromethyl)-1H-benzimidazole-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-2-{{4'-[(5,6-debtor-1H-benzimidazole-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-{[4'-(1H-benzimidazole-2-ylamino)-3'-fluoro-1,1'-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(5-methoxy-1H-benzimidazole-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; and
TRANS-(1R,2R)-2-[(3'-fluoro-4'-{[5-(trifluoromethyl)-1H-benzimidazole-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid.

9. The compound according to claim 1, selected from the group consisting of:
4-[4'-(1,3-benzoxazol-2-ylamino)-1,1'-biphenyl-4-yl]-4-oxo-2-(2-phenylethyl)butane acid;
2,2-dimethyl-4-{4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
4-{4'-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
4-{4'-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
2,2-dimethyl-4-{4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
2,2-dimethyl-4-{4'-[(4-methyl-1,3-benzoxazol-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
2,2-dimethyl-4-oxo-4-[4'-(5,6,7,8-tetrahydronaphthyl[2,3-d][1,3]oxazol-2-ylamino)-1,1'-biphenyl-4-yl]butane acid;
4-{4'-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
4-{4'-[(5-isopropyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
2,2-dimethyl-4-oxo-4-{4'-[(5-propyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}butane acid;
TRANS-2-({4'-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5,6-dimethyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-{[4'-(1,3-benzoxazol-2-ylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-chloro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(R,2R)-2-({4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-{1R,2R)-2-({4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-[(4'-{[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-{1S,2S)-2-({4'-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid;
TRANS-2-({4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid;
4-{4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butane acid;
TRANS-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-chloro-1,3-benzoxazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(5-fluoro-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-ft is R-4'-[(5-methyl-1,3-benzoxazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid; and
TRANS-(1R,2R)-2-[(3'-fluoro-4'-{[5-(trifluoromethyl)-1,3-benzoxazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid.

10. The compound according to claim 1 selected from the group consisting of:
4-[4'-(1,3-benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoic acid;
4-{4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
4-{4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
2,2-dimethyl-4-oxo-4-[4'-(1,3-thiazol-2-ylamino)-1,1'-biphenyl-4-yl]butane acid;
4-[4'-(1,3-benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]-2-(2-methoxyethyl)-4-oxobutanoic acid;
4-{4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2-(2-methoxyethyl)-4-oxobutanoic acid;
4-{4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2-(2-methoxyethyl)-4-oxobutanoic acid;
TRANS-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)CYCLOBUTANE-carboxylic acid;
TRANS-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
4-{4'-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
2,2-dimethyl-4-{4'-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
4-{4'-[(4-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
TRANS-(1R,2R)-2-{[4'-(1,3-benzothiazol-2-ylamino-1,1'-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;
TRANS-2-{[4'-(1,3-benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;
4-{4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butane acid;
2-(2-{4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2-oxoethyl)pentane acid;
TRANS-2-({4'-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(4-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
4-{4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2-[2-(dimethylamino)ethyl]-4-oxobutanoic acid;
2-[2-(dimethylamino)ethyl]-4-{4'-[(5-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
2-[2-(dimethylamino)ethyl]-4-{4'-[(6-nitro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
TRANS-2-{{4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-{{4'-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-{{4'-[(6-ethoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R2R)-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1S,2S)-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
2,2-dimethyl-4-{4'-[(5-nitro-1,3-thiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-4-oxobutanoic acid;
4-(4'-{[4-(4-chlorophenyl)-1,3-thiazol-2-yl]amino}-1,1'-biphenyl-4-yl)-2,2-dimethyl-4-oxobutanoic acid;
TRANS-(1R,2R)-2-({4'-[(4,6-debtor-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1S,2S)-2-({4'-[(4,6-debtor-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
CIS-3-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid;
CIS-3-({4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid;
TRANS-2-[(4'-{[6-(triptoreline)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1S,2S)-2-({4'-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-({4'-[(4,6-debtor-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}Carboni is)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-[(4'-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5,7-dimethyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-[(4'-{[6-(methylsulphonyl)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-2-({4'-[(5,6-dimethyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
4-{4'-[(6-ethoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
4-{4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}-2,2-dimethyl-4-oxobutanoic acid;
TRANS-2-({4'-[(5,7-debtor-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;
TRANS-(1R,2R)-2-[(4'-{[5-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-2-{[4'-(1,3-benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]carbonyl}cycle is propane-carboxylic acid;
TRANS-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexane-carboxylic acid;
TRANS-2-({4'-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;
TRANS-2-({4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;
TRANS-2-({4'-[(5,7-debtor-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;
TRANS-2-({4'-[(4,6-debtor-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;
TRANS-2-{[4'-(1,3-benzothiazol-2-ylamino)-1,1'-biphenyl-4-yl]carbonyl}CYCLOBUTANE-carboxylic acid;
TRANS-2-({4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)CYCLOBUTANE-carboxylic acid;
TRANS-2-({4'-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)CYCLOBUTANE-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-isopropyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-{[4'-(1,3-benzothiazol-2-ylamino)-3'-fluoro-1,1'-biphenyl-4-yl]carbonyl}cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(4,6-debtor-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1S,2S)-2-({4'-[(4,6-debtor-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-[(3'-fluoro-4'-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(4-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(5-chloro-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-methyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(5,7-dimethyl-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-({4'-[(5,7-debtor-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-[(3'-fluoro-4'-{[5-(trifluoromethyl)-1,3-benzothiazol-2-and the]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-(1R,2R)-2-[(3'-fluoro-4'-{[6-(triptoreline)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
TRANS-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)CYCLOBUTANE-carboxylic acid;
TRANS-2-{[4'-(1,3-benzothiazol-2-ylamino)-3'-fluoro-1,1'-biphenyl-4-yl]carbonyl}CYCLOBUTANE-carboxylic acid;
TRANS-2-{[4'-(1,3-benzothiazol-2-ylamino)-3'-fluoro-1,1'-biphenyl-4-yl]carbonyl}cyclopropane-carboxylic acid;
TRANS-2-({3'-fluoro-4'-[(6-methoxy-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopropane-carboxylic acid;
TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-isopropyl-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-({3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylic acid;
TRANS-2-[(3'-fluoro-4'-{[6-(trifluoromethyl)-1,3-benzothiazol-2-yl]amino}-1,1'-biphenyl-4-yl)carbonyl]cyclopentane-carboxylic acid;
4-{4'-[(6-chloro-1,3-benzothiazol-2-yl)amino]-3'-fluoro-1,1'-biphenyl-4-yl}-4-oxo-2-(2-phenylethyl)butane acid.

11. The compound of formula (1A)

where Q represents O, S or NH;
Rather it represents a linker selected from
,
where p is 1 or 2
and
,
where m is 0 and n is 1, 2, 3,or 4
R1and R2independently selected from hydrogen and ha is oida, (C1-C6)alkyl and (C1-C6)alkoxy;
R3and R4together with the carbon atoms to which they are attached, may form a benzene ring, optionally substituted with substituents in the number to two, selected from
halogen, (C1-C6)alkyl, (C1-C6)alkoxy, (C1-C6)haloalkyl, (C1-C6)alkylsulfonyl;
R6and R7both are (C1-C6)alkyl;
or
R6and R7together with the carbon atom to which they are attached, may form a 3-5 membered carbocyclic ring
or
6-membered ring, represented as

where W represents O;
or its pharmaceutically acceptable salts and esters.

12. The compound of formula (Ia) according to claim 11 where the compound has the structure:

13. The compound of formula (Ib)

where Q represents S or NR5;
Rather it represents a linker selected from
,
where p is 1 or 2 and
,
where m is 0 and is 1, 2, 3,or 4
or
m is 1 and p is 1, 2 or 3,
R1and R2independently selected from hydrogen, halogen and (C1-C6)alkyl;
R3and R4together with the carbon atoms to cotrim they connec the us, can form
benzene ring, optionally substituted with substituents in the number to two,
selected from
halogen, (C1-C6)alkyl, cyano, (C1-C6)haloalkyl and (C1-C6)alkylcarboxylic;
R5is a (C1-C6)alkyl;
R6represents hydrogen;
R7is a (C1-C6)alkyl, optionally substituted by phenyl;
or
R6and R7together with the carbon atom to which they are attached, may form a 3-5 membered carbocyclic ring;
or its pharmaceutically acceptable salts and esters.

14. Pharmaceutical composition having the properties of an inhibitor of DGAT-1, containing a therapeutically effective amount of a compound according to claim 1 or its pharmaceutically acceptable salt or ester in combination with a pharmaceutically acceptable carrier.

15. Medicinal product for the treatment and/or prevention of obesity, containing at least one compound according to claim 1 in combination with at least one pharmaceutically acceptable, pharmaceutically safe carrier or excipient.

16. The use of compounds according to claim 1 for the manufacture of a medicinal product for the treatment and/or prevention of obesity and obesity-related disorders.

17. The method of obtaining the compounds of formula (VII), incorporating the following stages:
interaction of the compounds of formula (II)

where R represents hydrogen or (C1-C6)alkyl;
X is a C1, Br or I; and
R1and As such as defined in claim 1;
with bronovil ether to obtain the compounds of formula (X)

where R represents hydrogen or (C1-C6)alkyl; and
R1and As such as defined in claim 1;
and combinations of the compounds of formula (X) with the compound of the formula (IX)

where R2, R3, R4and Q such as specified in claim 1;
in the presence of a palladium catalyst and optionally in the presence of a base to obtain the compounds of formula (VIII)

where R represents hydrogen or (C1-C6)alkyl,
R1, R2, R3, R4, And Q are such as defined in claim 1.

18. The method according to 17, where bronovil ether is pinacol borane and the base is potassium carbonate.

19. TRANS-(1R,2R)-2-({3'-fluoro-4'-[(6-fluoro-1,3-benzothiazol-2-yl)amino]
-1,1'-biphenyl-4-yl}carbonyl)-cyclopentanecarbonyl acid



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention concerns benzothiazole derivatives of general formula (I) and their pharmaceutically acceptable salts as adenosine receptor ligands and based medicinal product. 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 the general formula (I) , R1 is C5-C6-cycloalkyl substituted by CF3 group, lower alkyl, -(CH2)nOH or -(CH2)n-O- lower alkyl, or is 1-bicyclo[2,2,1]hept-2-yl, 1-(7-oxa-bicyclo[2,2,1]hept-2-yl, 1-(5-exo-hydroxybicyclo[2,2,1]hept-2-exo-yl, 1-(5-exo-hydroxybicyclo[2,2,1]hepto-2-endo-yl, or is 1-adamantane-1-yl; R2 is lower alkyl; or R1 and R2 together with N atom form 8-oxa-3-aza-bicyclo[3,2,1]octane group, n is 0 or 1.

EFFECT: improved efficiency of treatment.

9 cl, 2 dwg, 15 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: this invention refers to new compounds of formula (Ia) and to their pharmaceutically acceptable salts. Compounds of this invention are characterised by CB1 receptor antagonist properties. In formula (Ia) , R1 means phenyl independently mono-, di- or tri-substituted with haloid, (lower)alkoxy, (lower)alkyl, halogenated (lower)alkoxy or di(lower)alkylamino; R2 means phenyl, independently mono-, di- or tri-substituted with haloid, halogenated (lower)alkyl, nitro or cyano; R3 means hydrogen, nitro, amino, -NHSO2-R3a or -NHCO-R3b; R3a means (lower)alkyl, di(lower)alkylamino, benzyl, phenyl or phenyl monosubstituted with (lower)alkyl; R3b means benzyl or phenyl monosubstituted with (lower)alkyl.

EFFECT: application of compounds thereof as therapeutically active substance with CB1 receptor agonist properties and to relevant pharmaceutical composition.

18 cl, 1 dwg, 5 tbl, 70 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula II as neuropeptide FF receptor antagonist, their pharmaceutically acceptable acid-additive salts, medication based on them, as well as their application. Compounds can be applied for treatment and prevention of diseases mediated by activity of neuropeptide FF receptor, such as pain, hyperalgesia, enuresis, for elimination of syndromes arising in case of alcohol, psychotropic and nicotine addiction, for regulation of insulin release, digestion, memory functions, blood pressure or electrolytic and energy exchange. In general formula II , A together with thiazole ring forms 4,5,6,7-tetrahydrobenzothiazole, 5,6,7,8-tetrahydro-4H-cycloheptathiazole, 5,6-dihydro-4H-cyclopentathiazole fragments; R1 represents methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tret-butyl, 1,1-dimethylpropyl or phenyl; R2-R6 each represents hydrogen or methyl.

EFFECT: obtaining solutions, which ca be used for treatment and prevention of diseases, mediated by activity of neuropeptide FF receptor.

6 cl, 4 tbl, 106 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to an improved method for synthesis of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole. Method involves the following successive steps: (i) interaction of bromine with 4-acetamidocyclohexanone an aqueous solution to yield 2-bromo-4-acetamidocyclohexanone; (ii) addition of thiourea to yield 6-acetylamino-2-amino-4,5,6,7-tetrahydrobenzothiazole; (iii) addition of hydrobromic acid an aqueous solution to yield 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole without isolation of 6-acetylamino-2-amino-4,5,6,7-tetrahydrobenzothiazole synthesized at stage (ii); (iv) isolation of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole and if necessary separation of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole isolated at stage (iv) for R-(+)- and S-(-)-enantiomers, and isolation of R-(+)- and/or S-(-)-enantiomer. 2,6-Diamino-4,5,6,7-tetrahydrobenzothiazole is used for synthesis of pramipexole. Also, invention relates to a method for synthesis of pramipexole by synthesis of 2,6-diamino-4,5,6,7-tetrahydrobenzothiazole by using the method said and its conversion to pramipexole and if necessary by separation of pramipexole for its R-(+)- and S-(-)-enantiomers and isolation of R-(+)- and/or S-(-)-enantiomer.

EFFECT: improved method of synthesis.

15 cl, 1 sch, 3 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to compounds that possess affinity for adenosine A2A-receptors and represent compounds of the general formula: wherein R1 and R2 represent independently hydrogen atom, lower alkyl, tetrahydropyrane-2,3- or 4-yl, -(CH2)n-O-lower alkyl, -C(O)-lower alkyl, -(CH2)n-C(O)-lower alkyl, -(CH2)n-C(O)-NR'R'', -(CH2)n-phenyl substituted optionally with lower alkyl, lower alkoxy-group or -(CH2)n-pyridinyl, -(CH2)n-tetrahydropyrane-2,3- or 4-yl, -C(O)-piperidine-1-yl; or R1 and R2 in common with nitrogen atom (N) to which they are added form the ring 2-oxa-5-azabicyclo[2,2,1]hept-5-yl; R3 represents lower alkoxy-group, phenyl substituted optionally with halogen atom, -(CH2)n-halogen or -(CH2)n-N(R')-(CH2)n+1-O-lower alkyl, or represents pyridinyl substituted optionally with lower alkyl, halogen atom or morpholinyl; n means 1 or 2; R'/R'' represent independently of one another hydrogen atom or lower alkyl, and their pharmaceutically acceptable acid-additive salt. Except for, invention relates to a medicinal agent showing affinity to adenosine A2A-receptors containing one or some compounds by any claims 1-11, and pharmaceutically acceptable excipients.

EFFECT: valuable medicinal properties of compounds and agents.

13 cl, 38 ex

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for preparing a substituted alkylamine derivative from the 2-aminothiophenol compound with high industrial yield that can be used as an intermediate compound used in medicine or in agriculture. Invention proposes a method for preparing substituted alkylamine derivative represented by the following general formula (3): wherein X mean halogen atom, alkyl group, alkoxy-group, cyano-group or nitro-group; n means a whole number from 1 to 4; each R1 and R2 means independently hydrogen atom of phenyl-substituted, or unsubstituted alkyl group that can in common form 5- or 6-membered cycle, or its additive acid salt. Method involves addition of 2-aminothiophenol derivative salt represented by the following formula (1): wherein X and n have abovementioned values to acid to provide pH value 6 or less and to convert salt to free 2-aminothiophenol derivative of the general formula (1) followed by addition of 2-aminothiophenol derivative with amino-N-carboxyanhydride to the reaction represented by the following general formula (2): wherein each R1 and R2 have abovementioned values. Invention provides the development of a method for unimpeded preparing 1-(2-benzothiazolyl)-alkylamine derivative, i. e. substituted alkylamine derivative from the 2-aminothiophenol derivative with the satisfactory industrial yield and without pollution of the environment.

EFFECT: improved preparing method, valuable properties of compound.

8 cl, 13 ex

FIELD: medicine, organic chemistry.

SUBSTANCE: the present innovation deals with new benzothiazole derivatives and medicinal preparation containing these derivatives for treating diseases mediated by adenosine receptor A2.A.. The present innovation provides efficient treatment of the above-mentioned diseases.

EFFECT: higher efficiency of therapy.

14 cl, 354 ex

The invention relates to new derivatives of benzothiazole General formula (I) or its salt, where p denotes 1; X1and X2together form =O; R1denotes hydrogen, halogen, alkyl, alkoxy; R2denotes hydrogen; R3denotes a-Z4-R6, -Z13-NR7R8; Z4denotes a-Z11-C(O)-Z12-, -Z11-C(O)-O-Z12-; Z11and Z12represent a simple bond or alkylene; Z13denotes a-Z11-C(O)-Z12-; R4denotes hydrogen; R5denotes phenyl, substituted groups Z1, Z2selected from alkyl, halogen, nitro, -HE, hydroxyalkyl, -C(O)Z6, -C(O)OZ6-Z4-NZ7Z8where Z4represents a simple bond; biphenyl, substituted alkyl; naphthalenyl, which optionally can be substituted-HE; chinoline, substituted alkyl; heterocyclics; Z6denotes alkyl which may be optionally substituted by a group-Z4-NZ7Z8, morpholinium; Z7, Z8each independently represents alkyl; R6denotes alkyl optionally substituted by cyano, methoxy, phenyl, -Z4-NZ7Z8and so on; R7denotes hydrogen, alkyl; R8denotes alkyl, the long is Z4-NZ7Z8; and t

The invention relates to a new compound of the formula (I) in which one of the radicals R1- R5is HE, while the remaining radicals are H, to pharmaceutical compositions containing the said compound and said compounds as antiparasitic, antibacterial, antifungal and antiviral agents

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel compounds of the formula (I): and their pharmaceutically acceptable salts and esters wherein R1 means phenyl, naphthyl, 5-6-membered heterocyclyl comprising oxygen (O), nitrogen (N) or sulfur atom (S) as heteroatoms and wherein phenyl, naphthyl and heterocyclyl are optionally substituted with 1-3 substitutes chosen from halogen atom, (C1-C6)-alkyl, (C1-C6)-alkoxy, halogen-(C1-C6)-alkyl, halogen-(C1-C6)-alkoxy, nitro; di-(C1-C6)-alkylamino or (C1-C6)-alkoxy groups; R2 means hydrogen atom; R3 means (C1-C6)-alkyl or trifluoromethyl; A1 means C-R3 or nitrogen atom; A2 means piperidine or pyrrolidine wherein nitrogen atom in piperidine or pyrrolidine ring is added to A3 wherein A3 means -S(O)2- or -C(O)-; n = 0, 1 or 2. Also, invention relates to a pharmaceutical composition based on compounds proposed by the invention. Proposed compounds possess properties of NPY receptors antagonists and can be used in treatment arthritis, diabetes mellitus, nutrition disorders, obesity and others.

EFFECT: valuable medicinal properties of compounds and pharmaceutical composition.

16 cl, 1 tbl, 1 dwg, 26 ex

FIELD: organic chemistry, biochemistry, pharmacy.

SUBSTANCE: invention relates to novel cyclic compounds of the formula (I) and (II) or tier pharmaceutically acceptable salts wherein radical values given in formula (I) and (II) are indicated in the invention description. Also, invention relates to a pharmaceutical composition containing at least one compound of the formula (I), and to using these compounds for preparing a drug. Invention provides synthesis of novel compounds and preparing a compositions containing hereof that possess inhibitory activity with respect to protein-tyrosine kinase.

EFFECT: valuable medicinal and biochemical properties of compounds and pharmaceutical composition.

24 cl, 3 tbl, 582 ex

FIELD: organic chemistry, biochemistry, medicine, oncology, pharmacy.

SUBSTANCE: invention relates to novel diaminothiazoles of the formula (I) , their pharmaceutically acceptable salts and esters, and to a pharmaceutical composition based on thereof. Proposed compounds inhibit activity of cyclin-dependent kinase 4 (Cdk4), shows selectivity with respect to Cdk2 and Cdk1 and can be used in treatment against cancer, in particular, against solid tumors. In the general formula (I) R2 and R3 represent hydrogen atom; R4 is chosen from group comprising lower alkyl, (C3-C6)-cycloalkyl, O-lower alkyl, halogen atom, -NO2, S-lower alkyl, -CF3 and -CN; R5 is chosen from group comprising hydrogen atom, O-lower alkyl, lower alkyl, halogen atom and -OH, or, alternatively, R4 and R in common with two carbon atoms and a bond binding them belonging to benzene cycle (C) to which R4 and R5 are bound can form a cycle consisting of 5-6 atoms comprising one or two heteroatoms chosen from oxygen atom and optionally substituted with (C1-C4)-alkyl; R6 and R are chosen independently from group comprising hydrogen atom, lower alkyl and -COOR12, or, alternatively, group -NR6R7 can mean cycle consisting of 5-6 atoms optionally comprising heteroatom chosen from nitrogen or oxygen atoms; R8 and R9 are chosen independently from group comprising hydrogen atom and lower alkyl; R10 is chosen from group comprising hydrogen atom, lower alkyl, lower alkyl substituted with hydroxyl, and -COOR12; R11 is chosen from group comprising hydrogen atom, lower alkyl and -COOR12 wherein R12 means lower alkyl; m can mean 1 or 2; n can mean 0, 1 or 2 under condition that if m means 2 and R4 means fluorine atom then R5 is not hydrogen atom, and under condition if m means 1 and R4 means lower alkyl then R5 is not hydroxyl.

EFFECT: valuable biochemical and medicinal properties of compounds and pharmaceutical compositions.

20 cl, 6 sch, 3 tbl, 153 ex

FIELD: organic chemistry, medicine, oncology.

SUBSTANCE: invention relates to new derivatives of 2-arylimino-2,3-dihydrothiazoles of the general formula (I): wherein radical values R1, R2, R3 and R4 are given in the claim invention. New compounds are useful in treatment of pathological states or diseases wherein one or some somatostatin receptors are implicated, for example, acromegaly, hypophysis adenomas or gastroenteropancreatic endocrine tumors with carcinoid syndrome and gastroenteric bleedings.

EFFECT: improved preparing method, valuable medicinal properties of compounds and compositions.

14 cl, 2825 ex

FIELD: organic chemistry, pharmaceutical composition.

SUBSTANCE: new isoindoline-1-on-glucokinase activators of general formula I , as well as pharmaceutically acceptable salts or N-oxide thereof are disclosed. In formula A is phenyl optionally substituted with one or two halogen or one (law alkyl)sulfonyl group, or nitro group; R1 is C3-C9cycloalkyl; R2 is optionally monosubstituted five- or six-membered heterocyclic ring bonded via carbon atom in cycle to amino group, wherein five- or six-membered heteroaromatic ring contains one or two heteroatoms selected form sulfur, oxygen or nitrogen, one of which is nitrogen atom adjacent to carbon atom bonded to said amino group; said cycle is monocyclic or condensed with phenyl via two carbon atoms in cycle; said monosubstituted with halogen or law alkyl heteroaromatic ring has monosubstituted carbon atom in cycle which in not adjacent to carbon atom bonded to amino group; * is asymmetric carbon atom. Claimed compounds have glucokinase inhibitor activity and useful in pharmaceutical composition for treatment of type II diabetes.

EFFECT: new isoindoline-1-on-glucokinase activators useful in treatment of type II diabetes.

23 cl, 3 dwg, 43 ex

The invention relates to new and nitrate salts of heterocyclic compounds of formulas (a) and (b), where R is hydrogen, alkoxyl, R1- alkyl, alkoxyl, R2is hydrogen, alkyl, R3- alkyl, alkoxyl, X denotes N-R11or oxygen, R11means the free valence, Y represents N-R16, sulfur or alkyl, R16means hydrogen; other values radicals presented in the description of the invention

The invention relates to branched amino-thiazole, methods for their preparation and the pharmaceutical compositions

The invention relates to new thiazole derivative and pharmaceutically acceptable salts of these compounds, which possess pharmacological activity, processes for their preparation, pharmaceutical compositions comprising these compounds, and methods for their use
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