Glutamates as aggrecanase inhibitors

FIELD: chemistry.

SUBSTANCE: compound is a matrix metalloproteinase or aggrecanase. The invention also relates to a pharmaceutical composition based on said compounds and a method of treating osteoarthritis, (I), where W is -C(O)-; R1 is bisphenyl, possibly containing one or more substitutes R5 and R6; and if R1 contains one or more substitutes R5 and R6, the substitutes can be identical or different; R2 is hydrogen; R3 is -CO2H, -CONHOH, -CONHR7 or -COOR7; R4 is -CONR9R10; m equals 0. The values of substitutes R5-R7, R9, R10 are as described in the claim.

EFFECT: compounds have the capacity to modulate metalloproteinase activity.

18 cl, 40 ex, 18 dwg, 6 tbl

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

or its pharmaceutically acceptable salt, where
W represents-C(O)-;
R1represents a biphenyl, possibly containing one or more substituents R5or R6; and if R1contains more than one substituent R5or R6the substituents may be identical or different;
R2represents hydrogen;
R3represents-CO2H, -CONHOH, -CONHR7or-COOR7;
R4is a-CONR9R10;
R5is a (C6-C10)aryl, -NHCO-(C6-C10)aryl, -NHCO-heteroaryl where heteroaryl represents a 5-membered aromatic heterocyclic ring containing one heteroatom selected from oxygen, (C1-C6)alkyl, -O-(C1-C6)alkyl or-N-(C1-C6)alkyl, where each alkyl, aryl or heteroaryl may contain one or more substituents R6and if R5contains more than one substituent R6the substituents may be identical or different;
R6represents hydrogen, halogen, -OH, -CO2R7, (C2-C6)quinil, (C2-C6)alkenyl, -O-(C1-C )alkyl-(C3-C6)cycloalkyl, -O-(C1-C6)alkenyl, -O-(C1-C6)aryl, O-heteroaryl where heteroaryl represents a 5-membered saturated heterocyclic ring containing 2 heteroatoms selected from oxygen, and the specified ring condensed with a 6-membered aromatic ring, -O-(C1-C6)alkyl, containing as substituent (C6-C10)aryl, each aryl may contain one or more substituents R13;
R7represents hydrogen or (C1-C6)alkyl;
R9represents hydrogen or (C1-C6)alkyl may contain one or more substituents R12;
R10is a (C1-C6)alkyl may contain one or more substituents R12;
R12is a (C6-C10)aryl may contain one or more substituents R13A 5-membered saturated heterocyclic ring containing 2 heteroatoms selected from oxygen, where the specified ring condensed with a 6-membered aromatic ring;
R13represents a halogen, -O-(C1-C6)alkyl, -CO2H, -OH, -CF3hydrogen, (C1-C6)alkyl, (C6-C10)aryl, 5-6-membered heteroaryl containing 1 heteroatom selected from nitrogen and sulfur, (C2-C6 )alkenyl, (C2-C6)quinil, (C3-C6)cycloalkyl containing as Deputy-HE; (C6-C10)aryl containing as Deputy-NH2or (C6-C10)aryl containing as a substituent-O-(C1-C6)alkyl;
m is 0;
n is 0-4; and
p is 2.

2. The compound or pharmaceutically acceptable salt of the compound according to claim 1, wherein R3represents-CO2N.

3. The compound or pharmaceutically acceptable salt of the compound according to claim 1, characterized in that the compound or pharmaceutically acceptable salt of the compound is an S-enantiomer relative to the carbon atom to which the group R4.

4. The compound according to claim 1 of formula (Ia)

or its pharmaceutically acceptable salt, where
R1, R2and R4defined in claim 1.

5. The compound according to claim 4 or pharmaceutically acceptable salt, characterized in that
R4represents a

6. The compound according to claim 4 or pharmaceutically acceptable salt, characterized in that
R4represents a

7. The compound according to claim 4 or pharmaceutically acceptable salt, characterized in that
R4represents a

8. Joint who according to claim 1, wherein R13represents a halogen.

9. The compound according to claim 1, wherein R5represents -(C1-C6)alkyl.

10. The compound according to claim 1, wherein R6represents hydrogen.

11. The connection of claim 10, wherein R7represents hydrogen.

12. The compound according to claim 1, characterized in that
R4is a-CONR9R10;
R5represents -(C1-C6)alkyl;
R6represents hydrogen;
R7represents hydrogen;
R12is a (C6-C10)aryl;
R9represents hydrogen and
R10is a (C1-C6)alkyl, possibly substituted by one or more of R12.

13. The compound or its pharmaceutically acceptable salt according to claim 1, where the compound is selected from the following:
N1-benzyl-N2-[(4'-ethinyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-terbisil)-L-α-glutamine,
N1-benzyl-N2-[(2',5'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,4-dimethoxybenzyl)-L-α-glutamine,
N1-benzyl-N2-[(3',5'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-[(4'-ethyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-gluten is h,
N1-benzyl-N2-[(3'-ethoxy-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-[(2'-ethoxy-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-[(2',6'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(4-methoxybenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(3,4-acid)ethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(4-methoxyphenyl)ethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(1-naphthylmethyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3-methylbenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3-methoxybenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2,4-dichlorobenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(3-methoxyphenyl)ethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2,4-dimethoxybenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2-methoxybenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,4-dichlorobenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,5-diferensial)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N5-hydroxy-N1-[2-(3-methoxyphenyl)ethyl]-L-glutamate is,
N2-(1,1,-biphenyl-4-ylcarbonyl)-N5-hydroxy-N1-(3,4,5-trimethoxybenzyl)-L-glutamate,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,5-dimethoxybenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,5-dimethoxybenzyl)-N5-hydroxy-L-glutamate,
N1-benzyl-N2-[(4'-vinyl-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,4-dimethylbenzyl)-L-α-glutamine,
N1-benzyl-N2-[(4'-ethoxy-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-[(4'-propoxy-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-[(4'-butoxy-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-{[4'-(cyclobutylmethyl)-1,1'-biphenyl-4-yl]carbonyl}-L-α-glutamine,
N1-benzyl-N2-{[4'-(cyclohexylmethoxy)-1,1'-biphenyl-4-yl]carbonyl}-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,4-dimethylbenzyl)-N5-hydroxy-L-glutamate,
N2-{[4'-(acetylamino)-1,1'-biphenyl-4-yl]carbonyl}-N1-benzyl-L-α-glutamine,
N1-benzyl-N2-{[4'-(2-prolamine)-1,1'-biphenyl-4-yl]carbonyl}-L-α-glutamine,
N1-benzyl-N2-{4'-[(4-perbenzoic)amino]-1,1'-biphenyl-4-yl}carbonyl)-L-α-glutamine,
N2-{[4'-biphenyl-4-yl]carbonyl}-N1-benzyl-L-α-glutamine,
N2-[(2,2'-dimethyl-1,1'-biphenyl-4-yl)carbonyl]-N1-(3-methoxybenzyl)-L-α-gluta is in,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2-phenylethyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[3-(trifluoromethyl)benzyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-trifluoromethyl)benzyl]-L-α-glutamine,
N1-benzyl-N2-[(2-fluoro-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3-terbisil)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3-phenylpropyl)-L-α-glutamine,
N1-benzyl-N2-(1,1'-biphenyl-3-ylcarbonyl)-L-α-glutamine,
N1-benzyl-N2-[(3-chloro-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N1-benzyl-N2-[(2,6-dimethoxy-1,1'-biphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(3-chlorophenyl)ethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2-terbisil)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,4-diferensial)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2-methylbenzyl)-L-α-glutamine,
N1-benzyl-N2-({4'-[(methoxybenzyl)oxy]-1,1'-biphenyl-4-yl}carbonyl)-L-α-glutamine,
N1-benzyl-N2-({4'-[(3,5-dimethoxybenzyl)oxy]-1,1'-biphenyl-4-yl}carbonyl)-L-α-glutamine,
N1-benzyl-N2-{[4'-(2-aftermatket)-1,1'-biphenyl-4-yl]carbonyl}-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2,3-dimethylbenzyl)-L-α-glutamine,
N2-(1,1'-beef the Nile-4-ylcarbonyl)-N 1-(4-phenylbutyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(4-methylbenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[4-fluoro-3-(trifluoromethyl)benzyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3-jobensis)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3-vinylbenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)-1,1'-dimethylethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(4-tert-butylbenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(4-jobensis)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(4-vinylbenzyl)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(4-bromophenyl)ethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(2-biphenyl-4-retil)-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(2'-ethoxymethyl-4-yl)ethyl]-L-α-glutamine,
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-(3,3'-diphenylpropyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4'-methoxybiphenyl-3-yl)ethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4'-methoxybiphenyl-4-yl)ethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(3-bromophenyl)ethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1 N2-(biphenyl-4-ylcarbonyl)-N1-(1-methyl-1-phenylethyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)ethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4-chlorophenyl)ethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N1-benzyl-N2-(1,1'-biphenyl-4-ylcarbonyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[(1S)-1-(4-forfinal)ethyl]-L-α-glutamine,
tert-butyl N2-(biphenyl-4-ylcarbonyl)-N1-(1-phenylethyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[(1R)-1-(4-forfinal)ethyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[(1R)-1-phenylethyl]-L-α-glutamine,
N2-[(3'-ethoxymethyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(2-ethoxymethyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(4'-methoxybiphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(3'-ethoxymethyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
4'-{[((1S)-3-carboxy-1-{[(3,4,5-trimethoxybenzyl)amino]carbonyl}propyl)amino]carbonyl}biphenyl-3-carboxylic acid,
N2-[(4'-ethylbiphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(3',4'-dimethoxybiphenyl-4-yl)carbonyl]-N-(3,4,5-Tr is methoxybenzyl)-L-α-glutamine,
N2-[(2',4'-dimethoxybiphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N-(3,4,5-trimethoxybenzyl)-N2-[(3',4',5'-trimethoxyphenyl-4-yl)carbonyl]-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(3-methoxybiphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-[(3',4'-dimethoxybiphenyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(2'-ethoxymethyl-4-yl)carbonyl]-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(3'-fluoro-4'-methylbiphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-[(2',4'-dimethoxybiphenyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-[(3'-fluoro-4'-methylbiphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-({4'-[(3,5-dimethoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N-methyl-N-(2-phenylethyl)-L-α-glutamine,
N2-[(4'-Deut-butylbiphenyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N-2-[(4'-isopropylphenyl-4-yl)carbonyl]-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-(1,1:4',1"-terphenyl-4-ylcarbonyl)-L-α-glutamine,
N2-({4'-[(3,5-dimethoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-[(4'-hydroxybiphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(3'-methylbiphenyl-4-yl)carbon is l]-L-α-glutamine,
N2-({4'-[(3,5-dimethylbenzyl)oxy]biphenyl-4-yl}carbonyl)-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(4'-{[3,5-bis(trifluoromethyl)benzyl]oxy}biphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(3'-isopropylidene-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(4'-isopropylphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-[(3'-ethoxymethyl-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(3'-methoxybiphenyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(3'-isopropylidene-4-yl)carbonyl]-L-α-glutamine,
N2-[(3'-fluoro-4'-methylbiphenyl-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(4'-isobutylphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-1,1':4',1'-terphenyl-4-ylcarbonyl)-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N-benzyl-N2-{[3'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-L-α-glutamine,
N-benzyl-N2-({4'-[(3-terbisil)oxy]biphenyl-4-yl}carbonyl)-L-α-glutamine,
N-benzyl-N2-{[4'-(benzyloxy)biphenyl-4-yl]carbonyl}-L-α-glutamine,
N-(3,4,5-trimethoxybenzyl)-N2-[(2',4',6'-trimethylphenyl-4-yl)carbonyl]-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-({4'-[(3-methoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(4 hydroxybiphenyl-4-yl)carbonyl]-L-α-glutamine,
N-{1,1-dimethyl-2-phenylethyl)-N2-[(3'-ethoxymethyl-4-yl)carbonyl]-L-α-glutamine,
N2-({4'-[(3-methoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(4'-hydroxybiphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N-[2-(3,4-acid)ethyl]-N-methyl-L-α-glutamine,
N2-[(3'-hydroxybiphenyl-4-yl)carbonyl]-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-{[4'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(4'-methylbiphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-(4-forfinal)-1,1-dimethylethyl]-L-glutamate,
N2-({4'-[(3-tert-butylphenoxy)methyl]biphenyl-4-yl}carbonyl)-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-({4'-[(3,5-di-tert-butylphenoxy)methyl]biphenyl-4-yl}carbonyl)-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-({4'-[(3-ethylenoxy)methyl]biphenyl-4-yl}carbonyl)-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-({4'-[(3-methoxyphenoxy)methyl]biphenyl-4-yl}carbonyl)-L-α-glutamine,
N-[2-(4-forfinal)-1,1-dimethylethyl]-N2-[(3'-hydroxybiphenyl-4-yl)carbonyl]-L-α-glutamine,
N2-(biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)-1,2-dimethylethyl]-N5-hydroxy-L-glutamate,
N2-[(3',4'-diferuloyl-4-yl)carbonyl]-N-[2-(4-forfinal)-11-dimethylethyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(3',4'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',4'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',5'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',6'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(3',5'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',3'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N2-[(3',4'-diferuloyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-[(3',5'-diferuloyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-{[4'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-{[4'-(methyl bromide)biphenyl-4-yl]carbonyl}-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-{[4'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-N-(3-methylbenzyl)-L-α-glutamine,
N2-{[3'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-N-(3-methylbenzyl)-L-α-glutamine,
N2-[(3'-chloro-4'-forbiden-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N2-{[3'-(methyl bromide)biphenyl-4-yl]carbonyl}-N-(3-methylbenzyl)-L-α-glutamine,
N2-[(3'-chlorobiphenyl-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N2-[(4'-chlorobiphenyl-4-yl)carbonyl]-N-[2-(4-FPO is phenyl)-1,1-dimethylethyl]-L-α-glutamine,
N2-[(4'-forbiden-4-yl)carbonyl]-N-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N2-[(3'-forbiden-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N2-[(4'-chlorobiphenyl-4-yl)carbonyl]-N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-L-α-glutamine,
N2-[(3'-chlorobiphenyl-4-yl)carbonyl]-N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-L-α-glutamine,
N-(1,1-dimethyl-2-phenylethyl)-N2-[(4'-forbiden-4-yl)carbonyl]-L-α-glutamine,
N2-[(4'-{[3,5-bis(trifluoromethyl)phenoxy]methyl}biphenyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-({4'-[(1,3-benzodioxol-5-yloxy)methyl]biphenyl-4-yl}carbonyl)-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-{[3'-(benzyloxy)biphenyl-4-yl]carbonyl}-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-({3'-[(3,5-dimethoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-({3'-[(3-methoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine,
N2-({4'-[(3,5-dimethoxybenzyl)oxy]biphenyl-4-yl}carbonyl)-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N-benzyl-N2-{[4'-(biphenyl-3-ylethoxy)biphenyl-4-yl]carbonyl}-L-α-glutamine,
N-benzyl-N2-({4'-[(3'-methoxybiphenyl-3-yl)methoxy]biphenyl-4-yl}carbonyl)-L-α-glutamine,
N2-({4'-[(3,5-dimethoxyphenoxy)methyl]biphenyl-4-yl}carbonyl)-N-(3-methylbenzyl)-L-α-glutamine,
N2-({3'-[(3,5-dimethoxyphenoxy)methyl]biphenyl-4-yl}ka is bonyl)-N-(3-methylbenzyl)-L-α-glutamine,
N2-[(3'-{[3,5-bis(trifluoromethyl)phenoxy]methyl}biphenyl-4-yl)carbonyl]-N-(3-methylbenzyl)-L-α-glutamine,
N2-({3'-[(3-ethylenoxy)methyl]biphenyl-4-yl}carbonyl)-N-(3-methylbenzyl)-L-α-glutamine,
N-benzyl-N2-{[4'-(biphenyl-2-ylethoxy)biphenyl-4-yl]carbonyl}-L-α-glutamine and
N-benzyl-N2-({4'-[(3'-methoxybiphenyl-2-yl)methoxy]biphenyl-4-yl}carbonyl)-L-α-glutamine.

14. The compound or pharmaceutically acceptable salt of the compound according to item 13, where the compound is selected from the following:
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)1,1-dimethylethyl]-L-α-glutamine,
N2-[(3',4'-diferuloyl-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(3',4'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',4'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',5'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',6'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[3',5'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',3'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N2-[(3',4'-diferuloyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-[(3',5'-diferuloyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-gluten is h,
N2-{[4'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine.

15. The composition for modulating the activity of metalloproteinases, which is a matrix metalloproteinase or aggrecanases containing an effective amount of a compound or pharmaceutically acceptable salt of the compound according to claim 1, and a pharmaceutically acceptable carrier.

16. The composition according to item 15, wherein the compound or pharmaceutically acceptable salt of the compounds selected from the following:
N2-(1,1'-biphenyl-4-ylcarbonyl)-N1-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N2-[(3',4'-diferuloyl-4-yl)carbonyl]-N-[2-(4-forfinal)-1,1-dimethylethyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(3',4'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',4'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',5'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',6'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(3',5'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N-[2-(4-chlorophenyl)-1,1-dimethylethyl]-N2-[(2',3'-diferuloyl-4-yl)carbonyl]-L-α-glutamine,
N2-[(3',4'-diferuloyl-4-yl)carbonyl]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-[(3',5'-diferuloyl-4-yl)carbon is l]-N-(1,1-dimethyl-2-phenylethyl)-L-α-glutamine,
N2-{[4'-(hydroxymethyl)biphenyl-4-yl]carbonyl}-N-(3,4,5-trimethoxybenzyl)-L-α-glutamine.

17. The composition according to item 15, wherein the pharmaceutically acceptable carrier is suitable for oral administration, the composition is presented in a dosage form for oral administration.

18. A method of treatment of osteoarthritis, including the introduction of an effective dose of a compound according to claims 1 to 14 or its pharmaceutically acceptable salt.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: pharmaceutical compositions containing at least one compound of formula (IIIa) or (IIIb) or (IVa) or (IVb), where -X- and Y are described in the claims, or pharmaceutically acceptable salts, esters or amides thereof and a pharmaceutically acceptable carrier, which can be used in processes with modulation or E- and P-selectin expression.

EFFECT: obtaining low-molecular non-glycoside and non-peptide compounds, capable of creating antagonism to selectin-mediated processes.

11 cl, 38 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to chemical-pharmaceutical industry. Pharmaceutical compositions including, at least, one compound of formula where -X- represents, for instance, group of formula and Y represents, for instance, group of formula or its pharmaceutically acceptable salts, esters or amides, or pro-drugs and pharmaceutically acceptable carrier, which is acceptable in therapy, can be applied for modulation in vitro and in vivo processes of binding, mediated by binding of E-, P- or L- selectin.

EFFECT: obtaining novel floroglucin derivatives.

9 cl, 10 ex, 3 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula Ia and their pharmaceutically acceptable salts, hydrates, solvates, esters and amides. In formula Ia , A is specified from -C(O)OR5 where R5 represents hydrogen; W represents C1-3alkylene; Y is specified from phenyl and 5-6-member heteroaryl containing one heteroatom specified from N, S, O; where any phenyl or heteroaryl Y can be optionally substituted with 1 to 3 radicals specified from halogen, C1-6alkyl, C1-6alkoxygroup, halogen-substituted C1-6alkyl and halogen-substituted C1-6alkoxygroup; Z is specified from: where left and right asterisks Z specify an attachment point between -C(R3)(R4)- and A of formula la; R6 is specified from hydrogen and C1-6alkyl; or R6 can be attached to carbon atom in Y to form a 5-7-member ring; R1 is specified from phenyl and 5-member heteroaryl containing one heteroatom specified from S, O; where any phenyl or heteroaryl R1 is substituted with a radical specified from phenylC0-4alkyl, heteroarylC0-4alkyl where heteroaryl represents 5-6-member heteroary containing one heteroatom specified from N, S, O, C3-8cycloalkylC0-4alkyl, C3-8heterocycloalkylC0-4alkyl which contains nitrogen atom as heteroatom, or C1-6alkyl; where any phenyl, heteroaryl, cycloalkyl or heterocycloalkyl group R1 can be optionally substituted with 1 to 3 radicals specified from halogen, C1-6alkyl, C1-6alkoxygroup, halogen-substituted C1-6alkyl group and halogen-substituted C1-6alkoxygroup; R2 represents C1-6alkyl group; R3 and R4 represent hydrogen.

EFFECT: preparation of the pharmaceutical composition exhibiting EDG/S1P receptor modulating properties, containing therapeutically effective amount of the compound under the invention, development of a method of treating the disease mediated by EDG/S1P receptor activity, application of the compounds for preparing a drug for prevention or treatment of the disease mediated by EDG/S1P receptor activity.

16 cl, 1 tbl, 86 ex

FIELD: chemistry.

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

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

11 cl, 30 ex

FIELD: medicine.

SUBSTANCE: invention relates to amidines of formula (I) and to their derivatives, methods for making thereof and pharmaceutical compositions containing amidines of formula (I). According to said invention, amidines are applicable for inhibition of IL-8 induced chemotactic factor, and can be applied to produce medicine agents for treating psoriasis, ulcerative colitis, melanoma, chronic obstructive pulmonary disease (COPD), bullous pemphigoid, rheumatoid arthritis, idiopathic fibrosis, glomerulonephritis and for preventing and treating injuries caused by ischemia and reperfusion.

EFFECT: higher clinical effectiveness.

7 cl, 6 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula (I), including its pharmaceutically acceptable salts, solvates, ethers and amides, possessing ability to bind ERα- and ERβ-estrogen receptors, to pharmaceutical composition based on them, to versions of applying claimed compounds in medication preparation and to method of binding ERα- and ERβ-estrogen receptors. (I), where R1 represents H, OH or C1-12alkoxy, or halogen; R2 represents H, OH or halogen; R3 represents C1-12alkyl, halogeno-C1-12alkyl, C3-10cycloalkyl, C1-12alkoxy or C1-12alkoxyC1-12alkyl; R4 represents H or C1-12alkoxy; R5 represents H, halogen or halogeno-C1-12alkyl; R6 represents -(Y)z-R7; R8 represents phenyl or 5- or 6-member heteroaryl, containing N, O or S as heteroatom, where said phenyl and heteroaryl are possibly substituted with OH, halogeno, halogenoC1-12alkyl or C1-12alkoxy. Values R7, Y and z are presented in invention formula.

EFFECT: novel compounds possess useful biological properties.

19 cl, 7 dwg, 1 tbl, 70 ex

FIELD: chemistry.

SUBSTANCE: in acidified indanylamines of general formula (I) R1-R4 have values given in description, A represents CH2, CHOH, B represents CH2 and R5 represents aryl or heteroaryl group, possibly substituted with substituents, listed in description. Said compounds are useful in regulation of endothelial nitrogen oxide synthase (eNOS) and, therefore they can be useful for production of medications for treatment of stable and unstable angina pectoris, Prinzmetal's angina, acute coronary syndrome, impaired heart function, cardiac infarction, stroke, thrombosis, peripheral artery occlusive disease, endothelial dysfunction, atherosclerosis, hypertension, lung hypertension, symptomatic hypertension, renovascular hypertension, erectile dysfunction, diabetes or diabetes complications, nephropathy, retinopathy, limited memory function, limited learning ability.

EFFECT: increase of composition efficiency.

37 cl, 441 ex, 2 tbl

FIELD: organic chemistry, chemical technology, medicine.

SUBSTANCE: invention relates to a new method for synthesis of derivative of thieno[3,2-c]pyridine of the formula (1): (ticlopidine and clopidogrel). Method involves interaction of compound of the formula (2e): with compound of the formula (3): or its salt wherein R represents hydrogen atom or methoxycarbonyl; each among X' and Y' represents independently chlorine, bromine atom, methanesulfonyl or p-toluenesulfonyl, and to novel intermediate compounds and methods for their synthesis. Ticlopidine and clopidogrel possess the high inhibitory activity with respect to blood platelets aggregation and antithrombosis activity.

EFFECT: simplified process of synthesis, valuable medicinal properties of compounds.

15 cl, 32 ex

FIELD: organic chemistry, medicine, pharmacy.

SUBSTANCE: invention relates to novel ester compounds represented by the formula (1): wherein values for R1, R2, A, X, R3, R4, Alk1, Alk2, l, m, D, R8 and R9 are determined in the invention claim. Also, invention relates to inhibitor of matrix metalloproteinase (MTP), a pharmaceutical composition able to inhibit activity of MTP selectively, agents used in treatment or prophylaxis of hyperlipidemia, arteriosclerosis, coronary artery diseases, obesity, diabetes mellitus or hypertension wherein the pharmaceutical composition is prepared in capsulated formulation, and to a biphenyl compound of the formula (100) given in the invention description.

EFFECT: valuable medicinal properties of compounds.

53 cl, 78 tbl, 17 ex

FIELD: organic chemistry, pharmacy.

SUBSTANCE: invention relates to new biphenylsulfonylcyanamides of the formula (I): wherein R1 means: 1. (C1-C8)-alkyl; 4. -CnH2n-nn-Y wherein nn = 0 or 2 and n = 0-4, and n is not 0 or 1 if nn = 2; 5. CnH2n-nn-Y wherein nn = 0 or 2 and n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with amino-group or NR(22)R(23); R2 means: 2. (C1-C)-alkyl; 4. (C2-C12)-alkenyl; 5. (C2-C8)-alkynyl; 6. -CnH2n-nn-Z wherein nn = 0 or 2; n = 0-4, and n is not or 1 if nn = 2; 7. -CnH2n-nn-Z wherein nn = 0 or 2; n = 1-4, and n is not 1 if nn = 2, and 1 hydrogen atom in bivalent residue CnH2n-nn is substituted with a residue taken among a series: 1. phenyl; 3. NR(22)R(23); 5. COOR(16); R3 and R4 mean hydrogen atom; R5, R6 and R7 mean independently of one another hydrogen atom (H), (C1-C8)-alkyl; SO2-(C1-C4)-alkyl, F, Cl, Br, J, OR(10) wherein R(10) means hydrogen atom, (C1-C4)-alkyl that is substituted if necessary with methoxy- or ethoxy-group; R(9) means OR(13) wherein R(13) means hydrogen atom, H,(C1-C8)-alkyl;X means carbonyl group, -CO-CO- or sulfonyl group; Y and Z mean independently of one another: 1. phenyl, 1-naphthyl, 2-naphthyl; 2. one of residues determined in cl. 1 substituted with 1-5 similar or different residues taken among a series: phenyl, F, Cl, Br, J, CF3, SOqR(18), OR(16), NR(19)R(20), -CN, NO2, COR(9), or two residues form methylenedioxy-group; 3. furyl, thienyl, pyridyl, benzimidazolyl, indolyl, benzothiophenyl, dihydroquinazolinyl; 5. (C3-C10)-cycloalkyl wherein cyclopropyl, cyclopentyl, cyclohexyl and indalyl are preferable; 6. one of residues determined in cl. 5 substituted with phenyl; R(16) means: 1. hydrogen atom; 2. (C1-C4)-alkyl; 3. (C1-C4)-alkyl substituted with (C1-C4)-alkoxy-group; R(19) and R(20) mean independently: hydrogen atom (H), (C1-C4)-alkyl; R(22) and R(23) mean independently of one another hydrogen atom (H) or CO-OR(24) wherein R924) means -CnH2n-phenyl wherein n = 1-4; q = 2; and their physiologically acceptable salts. Compound of the formula (I) inhibit sodium-dependent chloride-bicarbonate exchange "NCBE".

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

4 cl, 2 tbl, 568 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds selected from a group comprising piperazine compounds of formula I: , where X is -CH2- or a bond; n equals 1; R1 is alkyl; cycloakyl; hydroxyethyl; benzo[1,3]dioxolyl; phenyl, which can be mono-substituted with a halide, alkyl, alkoxy, -CF3 or alkylcarbonyl; or phenyl which is di- or tri-substituted with substitutes independently selected from alkyl and halide; pyridyl which can be mono-substituted with a halide, alkyl or -CF3; furanyl which can be mono-substituted with methyl, hydroxymethyl or bromine, or furanyl which is disubstituted with an alkyl; thienyl which can be mono-substituted with methyl or chromium; pyrimidinyl; isoquinolinyl; benzhydryl; imidazolyl optionally mono-substituted with an alkyl; or thiazolyl; or X is -C(=O)- and R1 is hydrogen; R2 is indolyl, imidazolyl optionally mono-substituted with alkyl; phenyl which can be mono-substituted with a halide, alkyl, hydroxy or cyano, or phenyl which is disubstituted with a halide; pyridyl; benzothienyl; thiazolyl or thienyl; R3 is indolyl, pyridyl which can be mono-substituted with alkoxy, alkoxyalkoxy, NR31R32, morpholine, piperadine, oxopiperidinyl, oxopyrrolidinyl, pyridyl or phenyl; or phenyl which is mono-substituted with phenyl, pyridyl, alkyl, alkoxy, dialkylamino, morpholine, N-benzyl-N-alkylamino, (dialkylamino)alkoxy, phenylalkoxy or tetrahydroisoquinolinyl; or R3 denotes the group: , where Z is phenyl or pyridyl; R31 is 2-C1-C5alkoxyethyl, phenyl, pyridyl, phenylalkyl, hydroxyalkylcarbonyl, alkylcarbonyl, cycloalkylcarbonyl or phenylcarbonyl; R32 is hydrogen or methyl; R35 is alkyl, alkylcarbonyl, phenyl, pyridyl or pyrimidinyl; and R4 is phenyl-CH=CH-, where the phenyl can be mono-, di- or tri-substituted with substitutes independently selected from halide, alkyl, alkoxy and -CF3; or phenyl-CH2-CH2, where the phenyl is disubstituted with -CF3; and to optically pure enantiomers thereof, mixtures of enantiomers, such as, for example, racemates, optically pure diastereomers, mixtures of diastereomers, diastereomeric racemates, mixtures of diastereomeric racemates and mesoforms, such as salts of such compounds. The invention also relates to a pharmaceutical composition, as well as to use of compounds in any of claims 1-4.

EFFECT: obtaining novel biologically active compounds with antimalarial activity.

8 cl, 138 ex, 1 tbl

Aromatic compound // 2416608

FIELD: chemistry.

SUBSTANCE: invention describes a novel compound of general formula (1), where radicals R1, R2, X1, Y and A are as described in claim 1 of the invention. The invention also describes a method of obtaining compounds of formula (1), as well as a pharmaceutical composition based on said compounds, for treating fibrosis.

EFFECT: novel compounds with excellent collagen formation suppression, cause fewer side-effects and which are safer are obtained.

62 cl, 2717 ex, 432 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel bioisosteres of actinonin of general formula (I) , as well as to pharmaceutically acceptable salts thereof and pharmaceutical compositions based on said compounds, with peptide deformylase (PDF) inhibitory activity, as well as to use of the compounds or pharmaceutical compositions based on said compounds to prepare medicinal agents. In general formula (I) R1 is a hydrogen atom, R2 is a hydrogen atom, (C1-C6)alkyl residue, hetero(C1-C6)alkylphenyl residue, where the heteroatom is sulphur, R3 is a hydrogen atom, R4 is (C1-C6)alkyl residue, (C3-C7)cycloalkyl residue, R6 is a hydrogen atom, n is 1, 2 or 3. Values of substitute R5 are given in the formula of invention.

EFFECT: new compounds have useful biological activity.

8 cl, 1 ex

FIELD: pharmacology.

SUBSTANCE: claimed invention relates to compound of formula (I) in which m represents integer number, equal 1 or 2; R1 represents group, selected, in particular from phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl, thiazolyl, naphtyl, chinolinyl, isochinolinyl, benzisoxazolyl, tienopyridinyl, said group is possibly substituted with one or several groups of R3, similar or different from each other or by group R4, R2 represents group of general formula CHR5CONHR6, R3 represents halogen atom or one of the following groups: piano, nitro, C1-6-alkyl, C1-6-alkoxy, C1-6-trifluoralkyl, C1-6-trifluoralkoxy, benzyloxy, phenyloxy, R4 represents group, selected, in particular from phenyl, benzofuranyl, naphtyl; one orseveral groups R4 can by substituted with one or several groups R3, similar or different from each other; R5 represents hydrogen atom or C1-3-akyl group; R6 represents hydrogen atom or alkyl, C3-7-cycloalkyl or C3-7-cycloalkyl -C1-3-alkylene group; as base, salts of binding of acid, hydrate or solvate. Also invention relates to method of obtaining compound of formula I, its use as medicine and to based on it pharmacological composition.

EFFECT: novel derivatives of 1-pyperazine and 1-homopyperazincarboxilates, useful for prevention or treatment of pathology, in which endogen cannabinoids and/or any other substrates, metabolised by ferment FAAH, participate.

12 cl, 3 tbl, 11 ex

The invention relates to new derivatives of N, S-substituted N'-1-[(hetero)aryl] -N'-[(hetero)aryl] methylisothiazoline General formula I or their salts with pharmacologically acceptable acids HX in the form of a racemic mixture or in the form of a mixture of stereoisomers, which can be used for the treatment and prevention of diseases associated with dysfunction glutamatergic nanoperiodic

The invention relates to new derivatives of benzodioxole, benzofuran, dihydrobenzofuran and benzodioxane or their pharmaceutically acceptable solvate of General formula I

< / BR>
where Q1and Q2every means independently hydrogen or halogen;

X is CH2CH or oxygen;

Y represents CR3, CR3R4or (CH2)nwith n = 1-4;

Z denotes CH2CH or oxygen;

R means hydrogen, halogen or alkyl WITH1-4in both cases;

m denotes 1 or 2;

R1means1-6-alkyl, C3-6-cycloalkyl,1-3-haloalkyl,1-6-alkylamino,2-6alkenyl,1-4-alkoxy(C1-4)alkyl, C1-C4-alkylthio(C1-4)alkyl or triptorelin-C1-4;

R2means hydrogen, halogen or C1-4-alkyl; and

R3and R4each independently mean hydrogen or C1-4-alkyl,

containing pharmaceutical compositions for the treatment of sleep disorders, and disorders associated with disturbance of circadian rhythms

The invention relates to chemical agents regulating the growth and development of crops specifically for use as a growth promoter and herbicide new compounds of the formula

ClOCH2COOHH2N< / BR>
The claimed connection, its physico-chemical characteristics, method of production and application are not described in literature

The invention relates to new chemical compound is 5-amino-2-methylbenzothiazole-1,3(2-methoxy-3,6-sodium dichloro, benzoate formula

OHH2Nwhich can find application in agriculture as a herbicide

The invention relates to chemical means of plant protection, namely the compound of the formula

CH3OOCCOOHH2Nhave a weed-killing activity

FIELD: medicine, pharmaceutics.

SUBSTANCE: there are described compounds of 3-cyanonaphthalene-1-carboxylic acid and perhydroxyalkylmethylpiperazine of formula

, where R1 means C1-C4alkyl, R2 and R3 mean halogen, R4 is selected from the group consisting of 2-furanyl, 3-furanyl, 2-thiophen, 3-thiophen, phenyl, benzyl, 2-benzofuranyl, etc., R5 is selected from the group consisting of hydrogen and R6, R6 means a subgroup of general formula

which are antagonists of tachykinin receptors. Also, there are described pharmaceutical compositions containing such compounds, and methods for making such compounds and intermediate products for making the compounds according to said methods.

EFFECT: preparation of new compounds.

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (III): , in which D is a benzene ring, 2-pyridone ring, pyridine ring, benzoxalone ring, benzoxadinone ring or benzimidazole ring; R1 denotes carboxy or hydroxy; R2 independently denotes a halogen atom; alkyl optionally substituted with a halogen atom, aryl or alkylamine; alkynyl, optionally substituted alkoxy; hydroxy; carboxy; alkoxy optionally substituted with phenyl, aromatic heterocyclic ring which denotes a 5-6-member aromatic monocyclic carbocyclic ring containing one or two heteroatoms, independently selected from oxygen and nitrogen atoms; alkylsulphonyl; aryloxy; amino optionally substituted with alkyl; acyl optionally substituted with alkyl or alkyloxy; alkyloxycarbonyl; alkanesulphonyl; arylsulphonyl or alkylcarbamoyl; carbamoyl optionally substituted with alkyl, phenyl, cycloalkyl, acetyl, alkanesulphonyl, heteroarylalkyl, cycloalkylalkyl, heteroaryl which denotes a 5-6-member aromatic monocyclic ring containing one or three heteroatoms independently selected from oxygen and nitrogen atoms, and which is optionally substituted with alkyl or cycloalkyl; acylcyano; nitro, aryl; heteroaryl which denotes a 5-6-member aromatic ring containing one or more heteroatoms independently selected from oxygen, sulphur and nitrogen atoms, and which is optionally substituted with alkyl; alkylsulphonyl; morpholinylsulphonyl; non-aromatic heterocyclic group which denotes a 5-6-member non-aromatic heterocyclic ring containing one or more nitrogen atoms and optionally an oxygen and/or sulphur atom; R3 denotes C1-C6alkyloxy, C1-C6alkylthio; R4 denotes a halogen atom or alkyloxy; R5 denotes alkyl; M denotes sulphonyl; L3 independently denotes alkylene optionally containing one oxygen or nitrogen atom, alkenylene, or -N(R7)-; R7 independently denotes a hydrogen atom, alkyl; Y denotes a single bond or CO; Z denotes CH or N; n equals 0 or 1; p equals 0, 1, or 2; q equals 0 or 1; provided that R1 does not denote carboxy when ring D is a benzene ring, -L3- denotes -(O-alkylene)- and the substitution position of L3 and Y is an ortho-position in ring D; to pharmaceutically acceptable salts thereof. The invention also relates to compounds of formula (IV), a pharmaceutical composition, a method of treating diseases associated with the DP receptor, use of compounds in any of the claims 1-17, as well as compounds of general formula (V).

EFFECT: obtaining novel biologically active compounds having DP receptor antagonist activity.

30 cl, 8 ex, 62 tbl

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