Derivatives of aminopyrazol

FIELD: biotechnologies.

SUBSTANCE: invention relates to derivatives of aminopyrazol with the formula of , where A, E, R1 and R2 have values specified in the invention claims, and to their pharmaceutically acceptable salts. Compounds of the formula (I) are agonists of the ALX receptor. Besides, the invention relates to a pharmaceutical composition on the basis of the compound of the formula (I) or its pharmaceutically acceptable salt and to application of these compounds for production of a medicinal agent for prevention or treatment of a disease selected from inflammatory diseases, wheezing diseases, allergic states, HIV-mediated retrovirus infections, cardiovascular diseases, neuroinflammations, neurological disorders, pain, prion-mediated diseases and amiloid-mediated diseases; and for modulation of immune responses.

EFFECT: higher efficiency of compound application.

23 cl, 1 tbl, 466 ex

 

The text descriptions are given in facsimile form.

1. The compound of formula (I)

where a represents a phenyl or monocyclic heterocyclyl group, monocyclic heterocyclyl group selected from furanyl, oxazolyl, isoxazolyl tanila, thiazolyl and pyridyl, and where two atoms, phenyl or monocyclic heterocyclyl group that is attached to pyrazolidinone fragment and the remainder R2respectively, are isolated from each other using a single atom or a represents propan-1,3-diyl;
E represents *-C1-4alkyl-O-, -CH=CH - or

where the asterisks indicate the bond through which the connection occurs with R1;
Q represents O or S;
R3represents hydrogen, C1-4alkyl, cyclopropyl, C1-4Alcock and-C 1-2alkyl, -CH2NH2, -CH2NH, -CH2CH2(O)O-tert-Bu or benzyl;
R1represents heterocyclyl group selected from isoxazolyl, pyridyl, indolyl and benzothiazolyl, which is unsubstituted or mono - or disubstituted where the substituents independently chosen from halogen, C1-4the alkyl and C1-4foralkyl; or phenyl or naftalina group that is unsubstituted, mono-, di - or tizamidine, where the substituents independently selected from the group including halogen, C1-4alkyl, C1-4alkoxygroup,1-4foralkyl,1-4forelcosure, phenyl, cyano, di(C1-3alkyl)amino, -C(O)-NH2, -C(O)O-tert-Bu1-4alkoxy-C1-2alkyl, hydroxy-C1-2alkyl and dimethylamino-C1-2alkyl; and
R2represents a-CO-C1-3alkyl, -CO-cyclopropyl, -CF2-C1-3alkyl, -CHF-C1-3alkyl or-SO2-C1-3alkyl;
or pharmaceutically acceptable salt of such compounds.

2. The compound of formula (I) according to claim 1, where a represents furan-2,5-diyl, oxazol-2,4-diyl, oxazol-2,5-diyl, thiophene-2,4-diyl, thiophene-2,5-diyl, thiazol-2,4-diyl or pyridine-2,4-diyl; or a pharmaceutically acceptable salt of such compounds.

3. The compound of formula (I) according to claim 1, where a represents propan-1,3-diyl; or pharmaceutically acceptable the ol such connection.

4. The compound of formula (I) according to claim 1, where F is a

where the asterisk indicates the bond through which the connection occurs with R1;
or pharmaceutically acceptable salt of such compounds.

5. The compound of formula (I) according to claim 2, where E is a

where the asterisk indicates the bond through which the connection occurs with R1;
or pharmaceutically acceptable salt of such compounds.

6. The compound of formula (I) according to claim 1, where F is a *-C1-4alkyl-O-or-CH=CH-, where the asterisk indicates the bond through which the connection occurs with R1; or a pharmaceutically acceptable salt of such compounds.

7. The compound of formula (I) according to claim 1, where Q represents O; or a pharmaceutically acceptable salt of such compounds.

8. The compound of formula (I) according to claim 4, where Q represents O; or a pharmaceutically acceptable salt of such compounds.

9. The compound of formula (I) according to claim 5, where Q represents O; or a pharmaceutically acceptable salt of such compounds.

10. The compound of formula (I) according to claim 1, where R3represents hydrogen or methyl; or a pharmaceutically acceptable salt of such compounds.

11. The compound of formula (I) of claim 8, where R3represents hydrogen or methyl; or a pharmaceutically p is Jemima salt of such compounds.

12. The compound of formula (I) according to claim 9, where R3represents hydrogen or methyl; or a pharmaceutically acceptable salt of such compounds.

13. The compound of formula (I) according to claim 1, where R1represents phenyl, which is unsubstituted, mono-, di - or tizamidine, where the substituents independently selected from the group including halogen, C1-4alkyl, C1-4alkoxygroup,1-4foralkyl,1-4forelcosure, phenyl, cyano, dimethylaminopropyl, -C(O)O-tert-Bu and C1-4alkoxy-C1-2alkyl; or a pharmaceutically acceptable salt of such compounds.

14. The compound of formula (I) according to claim 11, where R1represents phenyl, which is unsubstituted, mono-, di - or tizamidine, where the substituents independently selected from the group including halogen, C1-4alkyl, C1-4alkoxygroup,1-4foralkyl,1-4forelcosure, phenyl, cyano, dimethylaminopropyl, -C(O)O-tert-Bu and C1-4alkoxy-C1-2alkyl; or a pharmaceutically acceptable salt of such compounds.

15. The compound of formula (I) indicated in paragraph 12, where R1represents phenyl, which is unsubstituted, mono-, di - or tizamidine, where the substituents independently selected from the group including halogen, C1-4alkyl, C1-4alkoxygroup,1-4foralkyl,1-4forelcosure, FeNi is, the cyano, dimethylaminopropyl, -C(O)O-tert-Bu and C1-4alkoxy-C1-2alkyl; or a pharmaceutically acceptable salt of such compounds.

16. The compound of formula (I) according to claim 1, where R2represents a-CO-C1-3alkyl or-CF2-C1-3alkyl; or a pharmaceutically acceptable salt of such compounds.

17. The compound of formula (I) 14 where R2represents a-CO-C1-3alkyl or-CF2-C1-3alkyl; or a pharmaceutically acceptable salt of such compounds.

18. The compound of formula (I) of clause 15, where R2represents a-CO-C1-3alkyl or-CF2-C1-3alkyl; or a pharmaceutically acceptable salt of such compounds.

19. The compound of formula (I) according to claim 1, selected from the group including
2-chlorbenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-chlorbenzoyl ether [1-(5-propiertary-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-chlorbenzoyl ether [1-(5-cyclopropanecarbonyl-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
benzyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
4-cryptomaterial ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3-cryptomaterial ether [1-(5-acetylfuran-2-ILM is Teal)-1H-pyrazole-3-yl]carbamino acid,
3-chlorbenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-4-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-ethylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2,6-dichlorobenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3,4-dimethylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3,4-differentialy ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-6-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
naphthalene-1-ymetray ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2,5-dimethylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2,4,6-tripersonality ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2,3-differentialy ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3-chloro-2,6-differentialy ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl] carbamino acid,
6-chloro-2-fluoro-3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3-chloro-2-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-6-fluoro-3-methylbenzyl the new ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2,4,5-tripersonality ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl] carbamino acid,
2,3,4-tripersonality ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
4-bromobenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-cryptomaterial ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
4-chlorbenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2,6-debtor-3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-phenylacrylate,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-chloro-6-forfinal)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2,3-acid)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2,3-dichlorophenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(3-trif ormeloxifene)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(3-chloro-4-forfinal)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-chloro-3,6-differenl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2,4-dichlorophenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-chloro-4-forfinal)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-methoxyphenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-fluoro-3-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-o-tolylacetate,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(3-chlorophenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(4-methoxyphenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-m-tolyloxy-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(3-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-methoxyphenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-p-tolylacetate,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(3-methoxyphenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-m-tolylacetate,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-methoxyphenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(4-methoxyphenyl)-2-metlox the evil-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-o-tolyloxy-4-carboxylic acid,
benzyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
4-cryptomaterial ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3-cryptomaterial ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3-chlorbenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl] carbamino acid,
2-chloro-4-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-ethylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,6-dichlorobenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3,4-dimethylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3,4-differentialy ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl] carbamino acid,
2-chloro-6-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
naphthalene-1-ymetray ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,5-dimethylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,4,6-tripersonality ether [1-(5-acetylfuran the-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,3-differentialy ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3-chloro-2,6-differentialy ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
6-chloro-2-fluoro-3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3-chloro-2-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,4,5-tripersonality ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,6-debtor-3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2,3,4-tripersonality ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
4-bromobenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-cryptomaterial ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
2-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
4-chlorbenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
3-methylbenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2 and the methyl)-1H-pyrazole-4-yl]-3-(2-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(4-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2-chloro-6-forfinal)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,3-acid)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,3-dichlorophenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(3-trifloromethyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2-chloro-3,6-differenl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,4-dichlorophenyl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2-chloro-4-forfinal)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-o-tolylacetate,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(3-chlorophenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(4-methoxyphenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-m-tolyloxy-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(4-methoxyphenyl)-2-methoxazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-m-tolyltriazole-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(3-triptoreline)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-methoxyphenyl)-2-methoxazole-4-carboxylic acid, [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2-chlorophenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-m-tolyloxy-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-p-tolylacetate,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-methoxyphenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-o-tolyloxy-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-chlorophenyl)thiazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(2-forfinal)thiazole-4-carboxylic acid,
2-chlorbenzoyl ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
1-phenethyl ester [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
4-bromobenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2-cryptomaterial ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2-tormentingly ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
4-chlorbenzoyl ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3-cryptomaterial ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3-chloro who entropy ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2-chloro-4-tormentingly ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2-ethylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2,6-dichlorobenzoyl ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3,4-dimethylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3,4-differentialy ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
naphthalene-1-ymetray ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2,5-dimethylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2,4,6-tripersonality ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2,3-differentialy ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3-chloro-2,6-differentialy ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
6-chloro-2-fluoro-3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
3-chloro-2-tormentingly ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2,6-debtor-3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2-fluoro-5-cryptomaterial ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
2,3,5-tripersonality ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]CT the amine acid,
2,3,4-tripersonality ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(5-oxohexyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-oxohexyl)-1H-pyrazole-4-yl]-3-(2-triptoreline)acrylamide,
(E)-N-[1-(5-oxohexyl)-1H-pyrazole-4-yl]-3-o-tolylacetate,
(E)-3-(2-chlorophenyl)-N-[1-(5-oxohexyl)-1H-pyrazole-4-yl]acrylamide,
[1-(5-oxohexyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-m-tolyloxy-4-carboxylic acid,
2-chlorbenzoyl ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
benzyl ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl] carbamino acid,
3-cryptomaterial ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
3-chlorbenzoyl ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-4-tormentingly ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
3,4-dimethylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
3,4-differentialy ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-6-tormentingly ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
naphthalene-1-ymetray ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2,5-dimethylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2,3-differenze the new ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
6-chloro-2-fluoro-3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
3-chloro-2-tormentingly ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2,6-debtor-3-methylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
2-ethylbenzylamine ether [1-(5-oxohexyl)-1H-pyrazole-3-yl]carbamino acid,
[1-(5-oxohexyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]-3-(2-triptoreline)acrylamide,
(E)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]-3-(4-triptoreline)acrylamide,
(E)-3-(2,3-dichlorophenyl)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]acrylamide,
(E)-3-(2,4-dichlorophenyl)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]acrylamide,
(E)-3-(2-chloro-4-forfinal)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]acrylamide,
(E)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]-3-o-tolylacetate,
[1-(5-oxohexyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-m-tolyloxy-4-carboxylic acid,
(E)-3-(3-chlorophenyl)-N-[1-(5-oxohexyl)-1H-pyrazole-3-yl]acrylamide,
2-chlorbenzoyl ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
{1-[-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
[1-(5,5-divergences)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
[1-(5,5-divergences)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-cyclopropyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-ethyl-5-phenyloxazol-4-carboxylic acid,
6-chloro-2-fluoro-3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
6-chloro-2-fluoro-3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
[1-(5,5-divergences)-1H-pyrazole-4-yl]amide of 2-methyl-5-phenyloxazol-4-carboxylic acid,
[1-(5,5-divergences)-1H-pyrazole-4-yl]amide of 2-methyl-5-m-tolyloxy-4-carboxylic acid,
(E)-N-[1-(5,5-divergences)-1H-pyrazole-3-yl]-3-(4-triptoreline)acrylamide,
(E)-N-[1-(5,5-divergences)-1H-pyrazole-3-yl]-3-(2-triptoreline)acrylamide,
2-chlorbenzoyl ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
2-chlorobenz levy ether [1-(5-forhekset)-1H-pyrazole-4-yl]carbamino acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-chlorophenyl)acrylamide,
6-chloro-2-fluoro-3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-chloro-6-fluoro-3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
6-chloro-2-fluoro-3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-m-tolyloxy-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-(4-methoxyphenyl)oxazol-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-(4-methoxyphenyl)-2-methoxazole-4-carboxylic acid,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}-3-(4-triptoreline)acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}-3-(2,3-acid)acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}-3-p-tolylacetate,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-(3-methoxyphenyl)-2-methoxazole-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-(3-chlorophenyl)thiazole-4-carboxylic acid,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}-3-(4-methoxyphenyl)acrylamide,
(E)-N-{1-[5(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-(3-triptoreline)acrylamide,
(E)-3-(2,3-dichlorophenyl)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-(2,3-acid)acrylamide,
(E)-3-(2-chloro-4-forfinal)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-p-tolylacetate,
(E)-3-(2,4-dichlorophenyl)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}acrylamide,
(E)-3-(2-chloro-6-forfinal)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}acrylamide,
(E)-3-(2-chloro-3,6-differenl)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}acrylamide,
(E)-3-(3-chlorophenyl)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl} acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-(2-fluoro-3-triptoreline)acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-m-tolylacetate,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-(3-methoxyphenyl)acrylamide,
(E)-N-{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}-3-(4-methoxyphenyl)acrylamide,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 2-methyl-5-phenyloxazol-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 2-methyl-5-m-tolyloxy-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}amide 2-methyl-5-m-tolyloxy-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-ylmethyl]-1H-pyrazole-3-yl}amide 5-(3-methoxyphenyl)-2-methoxazole-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}amide 5-(3-methoxyphenyl)oxazol-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}amide 5-(3-methoxyphenyl)oxazol-4-carboxylic acid,
{1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}amide 5-(4-methoxyphenyl)oxazol-4-carboxylic acid,
3-chloro-2-tormentingly ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
3-cryptomaterial ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
2-chloro-4-tormentingly ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2,6-debtor-3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
2-chloro-6-tormentingly ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-tormentingly ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
3-cryptomaterial ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
3-chlorbenzoyl ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
3-cryptomaterial ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2,6-debtor-3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-tormentingly ether {1-[5-(1,1-dottorati)fu is an-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-tormentingly ether [1-(5,5-divergences)-1H-pyrazole-3-yl}carbamino acid,
benzyl ether of {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl} carbamino acid,
3-cryptomaterial ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-tormentingly ether [1-(5,5-divergences)-1H-pyrazole-4-yl}carbamino acid,
3-chlorbenzoyl ether [1-(5,5-divergences)-1H-pyrazole-3-yl}carbamino acid,
3,4-dimethylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
2-ethylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
3-chlorbenzoyl ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2-ethylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-3-yl}carbamino acid,
benzyl ether of {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
benzyl ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
3,4-dimethylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
3-chlorbenzoyl ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2-mative zilavy ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
3,4-dimethylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
benzyl ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2,5-dimethylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-3-yl]carbamino acid,
2-ethylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
3-methylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2,5-dimethylbenzylamine ether [1-(5,5-divergences)-1H-pyrazole-4-yl]carbamino acid,
2-ethylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
3-methylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
2,5-dimethylbenzylamine ether {1-[5-(1,1-dottorati)furan-2-ylmethyl]-1H-pyrazole-4-yl}carbamino acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2,4-acid)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-forfinal)-2-methoxazole-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-chlorophenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-and ethylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3,4-dimetilfenil)oxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,4-acid)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3,4-dimetilfenil)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-forfinal)-2-methoxazole-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(4-methoxyphenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-(3-triptoreline)oxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(4-chlorophenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-chlorophenyl)-2-methoxazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-biphenyl-3-yl-2-methoxazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-p-tolyloxy-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-p-tolyloxy-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-(3-triptoreline)oxazol-4-carboxylic acid,
4-tormentingly ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
3-bromobenzylamine ether [1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
4-tormentingly ether [1-(5-acetylfuran-2-metil)-1H-pyrazole-4-yl]carbamino acid,
3-bromobenzylamine ether [1 -(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,3-debtor-4-triptoreline)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,5-debtor-4-methoxyphenyl)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(4-triptoreline)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl] amide 5-(3-triptoreline)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-forfinal)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(4-chlorophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(4-forfinal)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(4-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(4-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-triptoreline)oxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-chloro-3,5-differenl)acrylamide,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(2,5-debtor-4-triptoreline)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(4-chlorophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2 elmete is)-1H-pyrazole-4-yl]amide 5-(3-chlorophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-chlorophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-forfinal)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl] amide 5-biphenyl-3-yl-2-methoxazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl] amide 5-(3-chlorophenyl)-2-methoxazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-biphenyl-3-isoxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-biphenyl-3-isoxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-methoxyphenyl)-2-methoxazole-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-m-tolyloxy-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(3-acetylisoniazid-5-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(6-acetylpyridine-2-ylmethyl)-1H-pyrazole-4-yl] carbamino acid,
[1-(6-acetylpyridine-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(6-acetylpyridine-2-ylmethyl)-1H-pyrazole-4-yl]-3-(4-triptoreline)acrylamide,
2-chlorbenzoyl ether [1-(3-acetylphenyl)-1H-Piras the l-4-yl]carbamino acid,
[1-(3-acetylphenyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-pyridin-2-isoxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]-3-(4-triptoreline)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-cyanophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-carbamoylphenoxy)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-dimethylaminophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-triptoreline)acrylamide,
2-chlorbenzoyl ether [1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-[3-(2-methoxyethyl)phenyl]oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-cyanophenyl)oxazol-4-carboxylic acid,
tributyl ester 3-{4-[1-(5-acetylfuran-2-ylmethyl)-1-pyrazole-3-ylcarbonyl]oxazol-5-yl}benzoic acid,
2-chlorbenzoyl ether [1-(5-acetylpyridine-3-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-[3-(2-hydroxyethyl)phenyl]oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-methoxymethyl)oxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(4-acetylpyridine-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
tributyl ester {4-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-ylcarbonyl]-5-phenyloxazol-2-ylmethyl}carbamino acid,
2-chlorbenzoyl ether [1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)-N-[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-4-yl]-3-(4-triptoreline)acrylamide,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-aminomethyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-m-tolyloxy-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-m-tolyloxy-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methyl-5-m-tolyltriazole-4-ka is oil acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(4-chlorophenyl)-2-methylthiazole-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-cyanophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-cyanophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-dimethylaminophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-dimethylaminophenyl)oxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-cyclopropyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-cyclopropyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(3-methoxy-4-were)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-hydroxymethylene)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-[3-(2-dimethylaminoethyl)phenyl] oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-dimethylaminomethylphenol)oxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(2-acetylpyridine-4-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(5-acetylthiophene-3-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(2-acetylthiazole-4-ileti is)-1H-pyrazole-4-yl]carbamino acid,
(E)-N-[1-(6-acetylpyridine-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-triptoreline)acrylamide,
2-chlorbenzoyl ether [1-(6-acetylpyridine-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(2-herperidin-4-yl)oxazol-4-carboxylic acid,
[1-(5-methansulfonate-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-pyridin-4-isoxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(6-methylpyridin-2-yl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-methoxymethyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methoxymethyl-5-phenyloxazol-4-carboxylic acid,
tributyl ester {4-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-ylcarbonyl]-5-phenyloxazol-2-ylmethyl}carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-(6-triptorelin-2-yl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-isoxazol-5-isoxazol-4-carboxylic acid,
[1-(2-acetylthiazole-4-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-(2-methoxyethyl)-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-(2-methoxyethyl)-5-FeNi is oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-isopropyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-butyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-isopropyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-butyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-isopropoxyphenyl)oxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-[3-(2-isopropoxyphenyl)phenyl]oxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]carbamino acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]amide of 2-benzyl-5-phenyloxazol-4-carboxylic acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-benzyl-5-phenyloxazol-4-carboxylic acid,
tributyl ester 3-{4-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-ylcarbonyl]-5-phenyloxazol-2-yl}propionic acid,
[1-(5-acetylthiazole-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(5-acetylthiazole-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(2-acetylthiazole-5-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
(E)--[1-(2-acetylthiazole-5-ylmethyl)-1H-pyrazole-4-yl]-3-(4-triptoreline)acrylamide,
2-chlorbenzoyl ether [1-(2-acetylthiazole-5-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(2-acetyloxy-5-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
[1-(4-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]amide 5-phenyloxazol-4-carboxylic acid,
2-chlorbenzoyl ether [1-(4-acetylthiophene-2-ylmethyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-m-tolyloxy-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-chlorophenyl)-2-methoxazole-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-m-tolyloxy-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-phenyloxazol-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-(3-triptoreline)oxazol-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-forfinal)oxazol-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-dimethylaminophenyl)oxazol-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-chlorophenyl)oxazol-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide of 2-methyl-5-(3-trifloromethyl)oxazol-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-trifloromethyl)oxazol-4-carboxylic acid is you,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-methoxyphenyl)oxazol-4-carboxylic acid,
(E)-N-[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]-3-(4-triptoreline)acrylamide,
(E)-N-[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-triptoreline)acrylamide,
(E)-N-[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]-3-(3-trifloromethyl)acrylamide,
(E)-N-[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]-3-(2-chloro-4-forfinal)acrylamide,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-methoxyphenyl)-2-methoxazole-4-carboxylic acid,
[1-(4-acetylthiazole-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(3-forfinal)-2-methoxazole-4-carboxylic acid,
[1-(4-acetyloxy-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid,
{1-[4-(1,1-dottorati)thiazol-2-ylmethyl]-1H-pyrazole-3-yl}amide 5-phenyloxazol-4-carboxylic acid,
benzothiazole-2-ymetray ether [1-(5-oxohexyl)-1H-pyrazole-4-yl]carbamino acid,
[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-(6-triptorelin-2-yl)oxazol-4-carboxylic acid,
(E)-N-[1-(5-acetylfuran-2-ylmethyl)-1H-pyrazole-4-yl]-3-(1H-indol-3-yl)acrylamide,
[1-(5-acetyloxy-2-ylmethyl)-1H-pyrazole-3-yl]amide 5-phenyloxazol-4-carboxylic acid and
2-chlorbenzoyl ether [1-(2-acetyloxy-4-ylmethyl)-1H-pyrazole-4-yl]carbamino acid;
or pharmaceutically acceptable salt of such compounds.

20. The connection formula is (I) according to claim 1 or its pharmaceutically acceptable salt as a medicine, possessing activity as agonists ALX receptor.

21. Pharmaceutical composition containing as an active ingredient a compound of the formula (I) according to claim 1 or its pharmaceutically acceptable salt, and at least one therapeutically inert filler and having activity against ALX receptor.

22. The use of the compounds of formula (I) according to claim 1 or its pharmaceutically acceptable salt to obtain drugs for prevention or treatment of a disease selected from inflammatory diseases, obstructive respiratory tract diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular diseases, neurospine, neurological disorders, pain, prevaporizing diseases and amyloidogenic diseases; and to modulate immune responses.

23. The compound of formula (I) according to claim 1 or its pharmaceutically acceptable salt, intended for the prevention or treatment of a disease selected from inflammatory diseases, obstructive respiratory tract diseases, allergic conditions, HIV-mediated retroviral infections, cardiovascular diseases, neurospine, neurological disorders, pain, prion-mediated diseases and amyloid-mediated diseases; and to modulate immune responses.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention provides to a high degree a safe pharmaceutical drug which is effective for diseases caused by MMP-2 and/or MMP-9. The pharmaceutical drug contains, as an active ingredient, at least one member selected from a group which consists of thiazole derivatives of formula (1): where R1 is a phenyl group which can have 1-3 lower alkoxy groups as substitutes in the phenyl ring, and R2 is a pyridyl group which can have 1-3 carboxyl groups as substitutes in the pyridine ring, or salts thereof.

EFFECT: high activity and use when treating diseases such as fibrosis and pulmonary emphysema.

4 cl, 4 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I), stereoisomers, trans- and cis-isomers, racemates or pharmaceutically acceptable salts thereof, having modulating activity on histamine H3-receptors. In formula (I) m equals 0; one of R1 and R2 is selected from a group which includes hydrogen, C1-10alkoxycarbonyl, amido-, carboxy-, C3-8cycloalkyl, halogen, -NRARB, (NRARB)carbonyl, or a group of formula -L2-R6; the other of R1 and R2 is selected from a group which includes hydrogen, halogen; each of R3a and R3b is independently selected from a group which includes hydrogen; each of R4 and R5 is independently selected from a group which includes C1-10alkyl and C1-10hydroxyalkyl; or R4 and R5, taken together with a nitrogen atom to which each is bonded, form a heteroaromatic ring of the type (a) or (b), where Q1 is O or C; Q2 is -N(R20)-; R20 is selected from a group which includes hydrogen and C1-10alkoxycarbonyl; each of p1 and p2 is independently equal to 1, 2 or 3; each of q1, q2, q3, q4 and q5 are independently equal to 0, 1 or 2; and wherein each carbon atom in the ring is substituted with hydrogen or 0, 1 or 2 substitutes, independently selected from a group which includes hydrogen, hydroxy group, fluorine, C1-10alkyl, C1-10hydroxyalkyl and C1-10fluoroalkyl; R6 is a phenyl, heterocycle or heterocycloC1-4alkyl, wherein the heterocycle is a 4-6-member aromatic or non-aromatic ring which contains 1 or 2 heteroatoms independently selected from N, O and S, optionally condensed with a benzene ring, wherein the phenyl or heterocycle can be unsubstituted or optionally substituted with one or more substitutes independently selected from a group which includes C1-4alkoxy, C1-4alkyl, cyano, halogen and oxo-; L is a bond or C1-4alkylene; L2 is a bond, C1-4alkylene, -C(=O)-, -SO2N(R14a)-, -N(R14a)SO2-, -C(O)N(R14a)-, -N(Rl4a)C(O)- or -N(R15)-; R10 is selected from a group which includes hydrogen; R14a is selected from a group which includes hydrogen; R15 is selected from a group which includes hydrogen; and RA and RB are independently selected from a group which includes hydrogen, C1-10alkyl, C1-10acyl, C1-4halogenalkyl, C1-10alkoxycarbonyl, C3-8cycloalkyl and C3-8cycloalkylcarbonyl. The invention also relates to a pharmaceutical composition which contains compounds of formula (I), a method for selective modulation of effects of histamine H3-receptors, use of said compounds in producing a medicament for treating a condition or disorder modulated by histamine H3-receptors, as well as specific compounds of formula (I).

EFFECT: improved properties of compounds.

18 cl, 2 tbl, 154 ex

FIELD: chemistry.

SUBSTANCE: described are novel chiral cis-imidazolines selected from a group which includes 2-{4-[(4S,5R)-2-(2-tert-butyl-4-ethoxypyrimidin-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}-acetamide, [(4S,5R)-2-(2-tert-butyl-4-ethoxypyrimidin-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazol-1-yl]-[4-(1,1-dioxohexahydrothiopyran-4-yl)-piperazin-1-yl]-methanone, [(4S,5R)-2-(2-tert-butyl-4-ethoxypyrimidin-5-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazol-1-yl]-[4-(3-methanesulphonylpropyl)-piperazin-1-yl]-methanone, 2-{4-[(4S,5R)-2-(6-tert-butyl-4-ethoxypyridin-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperazin-1-yl}-N,N-bis-(2-methoxyethyl)-acetamide. 2-{1-[(48;5K)-2-(6-tert-butyl-4-ethoxypyridin-3-yl)-4,5-bis-(4-chlorophenyl)-4,5-dimethyl-4,5-dihydroimidazole-1-carbonyl]-piperidin-4-yl}-acetamide and others described by the general structural formula (I), and pharmaceutical composition containing said compounds.

EFFECT: compounds can be used as anti-cancer agents, particularly as agents for treating solid tumours.

8 cl, 217 ex

FIELD: chemistry.

SUBSTANCE: invention relates to an amide derivative of formula (I), where A is benzene or pyridine, where the benzene or pyridine optionally contain 1 or 2 or 3 identical or different substitutes selected from an alkyl containing 1-6 carbon atoms, a cycloalkyl containing 3-6 carbon atoms, an alkoxy containing 1-6 carbon atoms, a halogen atom, nitro, cyano, alkylsulphonyl containing1-6 carbon atoms, amino, cyclic amine selected from 1,1-di-oxoisothiazolidinyl, 2-oxooxazolidinyl, oxopyrrolidinyl, 1,1-dioxothiazinyl and 2-oxoimidazolidinyl optionally having a substitute selected from an alkyl containing 1-6 carbon atoms and an alkylcarbonyl containing a total of 2-7 carbon atoms, acylamino containing a total of 2-7 carbon atoms, and an alkylsulphonyl amino containing 1-6 carbon atoms, wherein the right-side bond is linked to the carbonyl and the left-side bond is linked to the nitrogen atom, R1 and R2 are identical or different and each is a hydrogen, an alkyl containing 1-6 carbon atoms and optionally containing 3 halogen atoms as substitutes, a cycloalkyl containing 3-6 carbon atoms, a phenyl, a halogen atom or a cyano group and R1 and R2 are not a hydrogen atom at the same time, R3 is a hydrogen atom, an alkyl containing 1-6 carbon atoms, an alkenyl containing 2-6 carbon atoms, a cycloalkyl containing 3-6 carbon atoms, or a halogen, R4a, R4b and R4c are each independently a hydrogen atom, an alkyl containing 1-6 carbon atoms, or an oxo, R5a, R5b and R5c are identical or different and each is a hydrogen atom, an alkyl containing 1-6 carbon atoms and optionally containing substitute(s) selected from phenyl, an alkoxy group containing 1-6 carbon atoms, optionally substituted with an alkoxy group containing 1-6 carbon atoms, a phyenylcarbonyloxy group and a hydroxy group, or a phenyl, X is a carbon atom (any of R4a, R4b and R4c can be bonded to a carbon atom, but the carbon atom is not substituted with oxo) or a nitrogen atom (if Y is a single bond, the nitrogen atom can be oxidised to form an N oxide), Y is a single bond, a carbonyl or an oxygen atom, Z1 and Z2 are each independently a carbon atom (substitute R3 is optionally bonded to a carbon atom) or a nitrogen atom, and m equals 1 or 2, a pharmacologically acceptable salt thereof. The amide derivative is used as a preventive/therapeutic drug for treating autoimmune diseases, inflammatory bowel diseases or osteoarthritis.

EFFECT: amide derivative which suppresses production of inductive type MMP-9.

14 cl, 4 tbl, 581 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: application describes prodrugs being 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}thio)-4-[4-(2-hydroxyethoxy)-phenyl]pyridine-3,5-dicarbonitryl derivatives, and a method for preparing them.

EFFECT: invention can find application in treating and/or preventing cardiovascular diseases.

8 cl, 4 tbl, 18 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing substituted pyrimidin-5-yl carboxylic acids of formula I and can be used in organic chemistry. The method is realised by reacting N-substituted guanidines and hetarylamidines with ethoxymethylene derivatives of 1,3-ketoesters according to a scheme given below (where the substitutes are as defined in the claim).

EFFECT: improved method of producing substituted pyrimidin-5-yl carboxylic acids of formula I.

2 tbl, 14 ex

FIELD: chemistry.

SUBSTANCE: invention relates to isoxazole-pyridine derivatives of formula , where X; R1; R2, R3, R4, R5 and R6 are as described in claim 1 of the invention and a pharmaceutically acceptable salt thereof. The invention also relates to a medicinal agent for treating diseases associated with the binding site of the GABA A α5 receptor based on compounds of formula I and use of said compounds in preparing a medicinal agent.

EFFECT: novel compounds are active towards the binding site of said receptor and are useful in treating cognitive disorders such as Alzheimer's disease.

22 cl, 372 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of formula I , wherein R2 means methyl, Y means carbon or nitrogen, and R1, R3 and R4 have the value specified in the patent claim. Also, the invention refers to a pharmaceutical composition for the use as a pharmaceutical drug having activity of a phosphatidylinositol-3-kinase inhibitor, to the use of the compounds of formula I for preparing the pharmaceutical drug for treating a disease mediated by phosphatidylinositol 3-kinase and to a method for preparing the compounds of formula I .

EFFECT: preparing the compounds of formula I possessing activity of the phosphatidylinositol-3-kinase inhibitor.

10 cl, 5 tbl, 51 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to compounds of general formula (I), wherein A represents a pyrrole group or a pyrazole group, and X represents a carbon atom or a nitrogen atom; R1 represents a carboxy group; R2 independently represents a group specified in a substitute group α; R3 independently represents phenyl(C1-C6alkyl)group substituted by, phenyl(C1-C6alkyl)group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α); m is equal to 0, 1, 2 or 3, n is equal to 0 or 1; each of R4, R5, R6 and R7 independently represents a hydrogen atom, C1-C6alkyl group or a halogen atom; B represents a substituted naphthyl group (wherein the substitute(s) represents (represent) 1-4 groups independently specified in the substitute group α), or the group represented by formula (II), wherein B1, B2 and α are those as specified in the patent claim. Also, the invention refers to a pharmaceutical composition possessing lipolysis inhibiting activity, to the use of the compounds of formula (I) in preparing a drug preparation for treating hyperlipidemia, dislipidemia, abnormal lipid metabolism, arteriosclerosis or type II diabetes mellitus and to a method of treating or preventing the mentioned diseases.

EFFECT: preparing the compounds of formula (I) possessing lipolysis inhibiting activity.

36 cl, 1 dwg, 1 tbl, 69 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of general formula (1) and pharmaceutically acceptable salts thereof, which exhibit inhibitory activity on phospholipase A2 enzyme and therefore have prostaglandin and/or leucotriene production suppressing action. In formula X is a halogen atom, cyano group, C1-C3 alkyl group, which can be substituted with halogen atoms, C1-C3 alkoxy group or hydroxy group, C2-C4 alkenyl group, C1-C3 alkoxy group or hydroxy group; Y is a hydrogen atom or C1-C3 alkyl group; Z is C1-C3 alkyl group; G is selected from formulae and , where in formulae (G2) and (G5) R4 is a hydrogen atom or C1-C6 alkyl group which can be substituted with halogen atoms; D is -NR10C(O)-, -C(O)NR10-, -S(O)2NR10- or -N(R11)-; R10 is a hydrogen atom; R11 is a hydrogen atom or C1-C3 alkyl group; A is a single bond, C1-C6 alkylene, which can be substituted with a phenyl group, or C2-C4 alkenylene; Q is a phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, S, optionally substituted with a benzene ring; R5, R6 and R7 all or independently denote a hydrogen atom, a halogen atom, C1-C6 alkyl group which can be substituted with halogen atoms, C1-C6 alkoxy group which can be substituted with halogen atoms, phenyloxy group, phenyl group or a 5-6-member aromatic heterocyclic group containing 1-3 heteroatoms selected from N, O, where said phenyl group and 5-6-member aromatic heterocyclic group can be substituted with a C1-C3 alkyl group which can be substituted with halogen atoms or a C1-C3 alkoxy group. The invention also relates to specific compounds, a medicinal agent, a pharmaceutical composition, a phospholipase A2 enzyme activity inhibitor and a treatment method.

EFFECT: improved method.

21 cl, 56 tbl, 561 ex

Amide compound // 2479576

FIELD: chemistry.

SUBSTANCE: compounds exhibit antagonistic activity towards the EP4 receptor, which enables use thereof as an active ingredient in a pharmaceutical composition for treating chronic kidney disease or diabetic nephropathy.

EFFECT: high efficiency of the compounds.

27 cl, 228 tbl, 86 ex

FIELD: chemistry.

SUBSTANCE: invention relates to organic chemistry and specifically to a method of producing α,ω-bis-(1,5,3-dithiazepinan-3-yl)-alkanes of general formula (1):

n=1-8, which involves reaction of α,ω-alkanediamines of general formula H2N-CH2-(CH2)n-NH2, where n=1-8, with tert-N-butyl-1,5,3-dithiazepinane in chloroform in the presence of a SmCl3·6H2O catalyst with molar ratio α,ω-alkanediamine:tert-N-butyl-1,5,3-dithiazepinane:SmCl3·6H2O = 10:20:(0.3-0.7) at room temperature (about 20°C) for 2.5-3.5 hours.

EFFECT: method of obtaining novel α,ω-bis-(1,5,3-dithiazepinan-3-yl)-alkanes which can be used as antibacterial, antifungual and antiviral agents, as biologically active complexing agents, selective sorbents and extractants of precious metals, special reagents for inhibiting bacterial activity in different process media (from light industry to oil industry).

1 cl, 1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to 3-aza-bicyclo[3.3.0]octane derivatives of formula , where R1 and R2 are hydrogen, C1-4alkyl or fluorine; R3 is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl, trifluoromethoxy group and halogen; 2,3-dihydrobenzofuranyl; 2,3-dihydrobenzo[1,4]dioxynyl; or isoxazolyl, pyridyl, indazolyl, benzofuranyl, benzoxazolyl, benzoisoxazolyl, benzothiazolyl, benzoisothiazolyl, pyrrolo[2,1b]thiazolyl, imidazo[ 1,2-a]pyridinyl or imidazo[2,1-b]thiazolyl, where said groups are unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, halogen and trifluoromethyl; A is or ; R4 is C1-4alkyl or -NR6R7; R6 is hydrogen or C1-4alkyl; R7 is hydrogen or C1-4alkyl; and D is a phenyl which is unsubstituted, mono- or disubstituted, where the substitutes are independently selected from a group comprising C1-4alkyl, C1-4alkoxy group, trifluoromethyl and halogen; or a pharmaceutically acceptable salt of such a compound. 3-aza-bicyclo[3.3.0]octane derivatives or a pharmaceutically acceptable salt thereof are used as a medicinal agent having the activity of orexin receptor antagonists.

EFFECT: novel 3-aza-bicyclo[3,3,0]octane derivatives as nonpeptide antagonists of human orexin receptors.

9 cl, 1 tbl, 85 ex

FIELD: chemistry.

SUBSTANCE: invention relates phenyl pyrrole derivatives formula (I) where: A denotes =NOR4, O; R4 denotes, C1-C6 alkyl; R1 denotes C1-C6 alkyl, C1-C6 alkoxy, halogen-C1-C6 alkyl, halogen-C1-C6 alkoxy, NH2, mono- C1-C6 alkylamino, halogen-mono-C1-C6 alkylamino, di(C1-C6 alkyl)amino, halogen-di-(C1-C6 alkyl)amino; or A and R1 together with the carbon atom with which they are bonded form a 5- or 6-member heterocyclic aromatic group or a heterocyclic group with partially or completely reduced saturation, which can be benzo-condensed, can contain 1-3 heteroatoms selected from N, O and S, which can be substituted and contain 1 or 2 α substitutes; R2 denotes phenyl which can be substituted with 1 or 2 α substitutes, or a 6-member heteroaryl group containing 1 or 2 N atoms, which can be substituted with 1 or 2 α substitutes; R3 denotes OH, C1-C6 alkoxy, values of α are given in claim 1, or a pharmaceutically acceptable salt thereof.

EFFECT: compounds exhibit glucokinase activating activity, which enables use thereof in treating diabetes.

51 cl, 1 tbl, 132 ex

FIELD: chemistry.

SUBSTANCE: invention relates to method of obtaining α,ω-bis-(1,5,3-dithiazepinan-3-yl)-alkanes, which can be applied as antibacterial, antifungal and antiviral agents, as biologically active complexing agents, selective sorbents and extractants of precious metals, special reagents for suppression of vital activity of bacteria in various technical media (from light industry to oil). Essence of method lies in interaction of α,ω-alkanediamine with 1,3,6-oxadithiapinane in presence of catalyst SmCl3·6H2O with mole ratio α,ω-alkanediamine : 1,3,6-oxadithiapinane : SmCl3·6H2O=10:20:(0.3-0.7) at temperature ~20°C and atmospheric pressure for 2.5-3.5 h. Output of α,ω-bis-(1,5,3-dithiazepinan-3-yl)-alkanes (1) constitutes 72-85%.

EFFECT: increase of compound application efficiency.

1 tbl, 1 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula or a pharmaceutically acceptable salt thereof, in which R1 denotes hydrogen or C1-6alkyl; R2 denotes isooxazolyl group, substituted with C1-6alkyl; RB denotes -CF3, -CHF2, -CH2F, or C1-6alkyl. The invention also relates to pharmaceutical compositions for treating cancer which contain the disclosed compounds.

EFFECT: obtaining novel compounds and a pharmaceutical compositions based on said compounds, which can be used in medicine for treating cancerous diseases.

15 cl, 77 dwg, 10 tbl, 13 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new substituted heteroaryl derivatives of general formula I: , wherein: A means N, CR7-10, with A at the most twice meaning N; W means O, S or NR4, the values B, C, R7-10 are presented in clause 1 of the patent claim. The method for preparing the compound I is described.

EFFECT: compounds show analgesic activity that enables using them for a variety of diseases, especially acute pain, neuropathic, chronic or inflammatory pain.

16 cl, 2 tbl, 307 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of general formula (I),

, where groups and radicals R1, R2 independently denote H, C1-8-alkyl or C3-7-cycloalkyl, where the alkyl or cycloalkyl group can be mono- or poly-substituted with identical or different groups R11; or R2 denotes a -CH2- or -CH2-CH2- bridge which is bonded with a group Y, and R1 is as defined above, or denotes a group selected from C1-4-alkyl-CO-, C1-4-alkyl-O-CO-, (C1-4-alkyl)NH-CO- or (C1-4-alkyl)2N-CO-, where the alkyl groups can be mono- or polyfluorinated; or R1 and R2 form an alkylene bridge such that R1R2N- denotes a group selected from: azetidine, pyrrolidine, piperdine, azepan, 2,5-dihydro-1H-pyrrole, 1,2,3,6-tetrahydropyridine, 2,3,4,7-tetrahydro-1H-azepine, 2,3,6,7-tetrahydro-1H-azepine, piperazine, in which the free amino group is substituted with R13, piperidin-4-one, morpholine, thiomorpholine, 4-C1-4-alkoxy iminopiperidin-1-yl and 4-hydroxy iminopiperidin-1-yl. Wherein, when R1 and R2 form an alkylene bridge, one or more H atoms in the alkylene bridge can be substituted with identical or different groups R14, and X denotes a C1-3-alkylene bridge which can contain one, two or three identical or different C1-3-alkyl substitutes; and Y denotes a group of subformula selected from: and , where the group can be mono-substituted with a substitute R20; Z denotes -CH2-CH2- or -C(=O)-CH2-; U, V both denote CH, one of groups U, V denotes N, and the other of U, V denotes CH, where CH can be substituted with L; and L independently denotes halogen, cyano or C1-3-alkyl; and k equals 0, 1 or 2; W is selected from a group consisting of -CH2-O- and -O-CH2-; B is selected from a group consisting of phenyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, tetrazolyl, furyl, thiophenyl and thiazolyl; each of which can be mono- or poly-substituted with identical or different substitutes R20; radicals R11, R13, R14, R20 assume values given in claim 1. The invention also relates to a pharmaceutical composition containing at least one compound of formula I and having action on MCH receptor.

EFFECT: disclosed pharmaceutical compositions are useful in treating metabolic disorders or eating disorders, especially obesity, bulimia, anorexia, hyperphagia and diabetes.

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted pyrimidine derivatives, having HIV replication inhibiting properties, or pharmaceutically acceptable salts thereof. In formula (1): R1 denotes hydrogen; R2 and R3 independently denote hydrogen; R7 and R8 denote C1-6alkyl; R4 denotes cyano; R9 denotes C1-6alkyl optionally substituted with cyano, C2-6alkenyl substituted with cyano, C2-6alkynyl optionally substituted with cyano; R5 denotes C1-6alkyl optionally substituted with Ar or Het; C2-6alkenyl optionally substituted with Ar or Het; C2-6alkynyl optionally substituted with Ar or Het; C3-7cycloalkyl; Ar; Het; R6 denotes H, Het; Y denotes -OR11, -NR12R13; R11 denotes hydrogen or C1-6alkyl optionally substituted with hydroxy, C1-6alkoxy or pyridyl; R12 denotes hydrogen or C1-6alkyl; R13 denotes hydrogen or C1-6alkyl; or R12 and R13 together with a nitrogen atom, which is substituted by said two substitutes, form a morpholinyl; imidazolyl; X denotes -NR1-; Het denotes 5- or 6-member completely saturated ring, where one or two ring members are heteroatoms, each independently selected from nitrogen and sulphur, and where the rest of the ring members are carbon atoms; and where any member of the heterocycle with a nitrogen heteroatom can optionally be substituted with C1-6alkyl; where the 5- or 6-member ring can optionally be annelated with a benzene or thiophene ring; each aryl independently denotes phenyl or phenyl substituted with one substitute selected from C1-6alkoxy.

EFFECT: high efficiency of using said compounds.

7 cl, 4 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing mono-(di-, tetra-)methyl-1,2-bis-(1,3,5-dithiazinan-5-yl)ethanes of general formula (1-3): , (1) R1=CH3, R2, R3, R4=H (2) R1, R3=CH3, R2, R4=H (3) R1, R2, R3, R4=CH3, which involves reaction of hydrogen sulphide-saturated aqueous solution of (37%) formaldehyde and acetaldehyde with 1,2-diaminoethane with molar ratio of initial reagents 1,2-diaminoethane: formaldehyde: acetaldehyde: hydrogen sulphide equal to 10:50:10:40 to obtain (1), 10:40:20:40 to obtain (2), 10:20:40:40 to obtain (3), at temperature 40°C and atmospheric pressure for 2.5-3.5 hours.

EFFECT: method of obtaining novel compounds which can be used as selective sorbents and extraction agents of precious metals, agents for protecting leather, fur and textile from biodeterioration, biologically active substances with respect to different microorganisms and sulphate-reducing bacteria.

1 cl, 1 tbl, 1 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to compounds of formula (I) or pharmaceutically acceptable salts thereof wherein A, R1, R2, R3 and m are specified in the patent claim. The present invention also refers to the number of specific compounds, and to a pharmaceutical composition containing the above compounds effective for inhibition of kinases, such as glycogen synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus kinase (JAK), AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

EFFECT: preparing the specific compounds and pharmaceutical composition containing the above compounds effective for kinase inhibition.

18 cl, 393 ex

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