Pyridine- or pyrimidine-2-carboxamide derivatives

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I) and pharmaceutically acceptable salts thereof. In formula (I) Y is C-R4 and Z is CH; or Y is C-R4 and Z is N; or Y is N and Z is CH; R1 is a 5- or 6-member ring of formula (II) or (III): R2 is H, C1-C7-alkyl; R3 is phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, which can possibly be substituted with one, two or three substitutes selected from a group consisting of: CN, CI, F, Br, CF3, CHF2, C1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd; R4 is H, C1-C7-alkyl; R5 is H, CI, F, Br, CN, CF3, CHF2, C1-C7-alkyl, -C3-C6-cycloalkyl, -(CH2)m-Re or -(CO)-NRiRj; R6 is C1-C7-alkyl; R7 is H, CI, F, CN or C1-C7-alkyl; Rc is -OH; Rd is C1-C7-alkyl; Re is -CH2F, -CHF2, -CF3, CN, C1-C7-alkoxy; Ri, Rj independently denote H or C1-C7-alkyl; m equals 1-4. The invention also relates to a medicinal agent having mGluR5a receptor antagonist properties, containing one or more of the disclosed compounds as an active component.

EFFECT: high efficiency of the medicinal agent.

24 cl, 208 ex

 

The text descriptions are given in facsimile form.

1. Compounds of General formula (I)

where Y represents C-R4and Z represents CH; or
Y represents C-R4and Z represents N; or
Y is N and Z represents CH;
R1represents 5 - or 6-membered ring, respectively, of formula (II) or (III):



R2represents H, C1-C7-alkyl;
R3represents phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, that may be substituted is ne, two, or three substituents selected from the group consisting of:
CN, Cl, F, Br, CF3, CHF2With1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF3, -S(O)2-Rd;
R4represents H, C1-C7-alkyl;
R5represents H, Cl, F, Br, CN, CF3, CHF2With1-C7alkyl, -C3-C6-cycloalkyl, -(CH2)m-Reor -(CO)-NRiRj;
R6represents a C1-C7-alkyl;
R7represents H, Cl, F, CN or C1-C7-alkyl;
Rcis a HE;
Rdrepresents a C1-C7-alkyl;
Rerepresents-CH2F, -CHF2, -CF3CN, C1-C7-alkoxy;
Ri, Rjindependently of one another are N or C1-C7-alkyl;
m is 1-4;
and their pharmaceutically acceptable salts.

2. Compounds according to claim 1 of General formula (I'):

where Z represents N or CH;
R1represents 5 - or 6-membered ring, respectively, of formula (II') or (III'):


R2represents H, C1-C7-alkyl;
R3represents phenyl, pyrazolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, possibly substituted by one or more substituents:
CN, Cl, F, Br, CF3, CHF2, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CH2F, -O-CHF2, -O-CF2, -O-CF3, -S(O)2-Rd;
R4represents H, C1-C7-alkyl;
R5represents H, Cl, F, Br, CN, CF3, CHF2With1-C7-alkyl, -C3-C6-cycloalkyl, or -(CH2)m-Re;
R6represents a C1-C7-alkyl;
R7represents H or F;
Rcis a HE;
Rdrepresents a C1-C7-alkyl;
Rerepresents-CH2F, -CHF2or-CF3;
m is 1-4;
and their pharmaceutically acceptable salts.

3. Compounds according to claim 1 of formula (I), where
Y represents C-R4and Z represents CH; or
Y represents C-R4and Z represents N; or
Y is N and Z represents CH;
R1is as defined for formula (I) above;
R2represents N or C1-C7-alkyl;
R3represents phenyl, PI is azolyl, isoxazolyl, pyridinyl, pyrimidinyl or pyrazinyl, possibly substituted by one, two, or three substituents, independently selected from the group consisting of CN, Cl, F, CF3With1-C7-alkyl, -O-C1-C7-alkyl, -(CH2)m-Rc, -O-CF3, -S(O)2-Rd;
R4represents N or C1-C7-alkyl;
R5represents H, Cl, CN, CF3, CHF2With1-C7-alkyl, C3-C6-cycloalkyl, -(CH2)m-Reor -(CO)-NRiRj;
R6represents a C1-C7-alkyl;
R7represents H, Cl, F, CN, C1-C7-alkyl;
Rcis a HE;
Rdrepresents a C1-C7-alkyl;
Rerepresents-CF3CN, C1-C7-alkoxy;
Ri, Rjindependently of one another are N or C1-C7-alkyl;
m represents 1;
and their pharmaceutically acceptable salts.

4. Compounds according to claim 1 of formula (Ia):

where Y, Z, R2, R3, R5and R7are as defined in claim 1 or 3.

5. Compounds according to claim 4 of the formula (1A), where they are selected from the group consisting of:
(4-Methyl-thiazol-2-yl)-amide 4-(3-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,5-dif is the PR-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3-cyano-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-chloro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(2,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3-methoxy-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-methyl-4-(3-triptoreline-phenyl)-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3-methanesulfonyl-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(4-methoxy-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,4-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-methyl-4-(3,4,5-Cryptor-phenyl)-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(4-cyano-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(2-methoxy-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(2-chloro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3-hydroxymethyl-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,5-dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-methyl-4-pyrimidine-5-yl-pyridine-2-carboxylic sour is s;
(4-Methyl-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-(3,5-debtor-phenyl)-2-methyl-pyrimidine-4-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2-methyl-6-pyridin-3-yl-pyrimidine-4-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl~2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6'-methyl-[2,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-methyl-4-(3-trifluoromethyl-phenyl)-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2-chloro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 5-cyano-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,5-dimethyl-isoxazol-4-yl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4,6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 5-methoxy-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 4-(3-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 4-(3-cyano-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 4-(2-chloro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Trifluoromethyl-thiazol-2-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-6-methyl-pyridine-2-carboxylic acid;
(4-Deformity-thiazol-2-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Deformity-thiazol-2-yl)-amide 2'-chloro-6-methyl-[4,4'] bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 5-fluoro-3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 3,6-dimethyl-4-pyrimidine-5-yl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,4-ditto is-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2'-chloro-3,6-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 3,6,2'-trimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6'-methyl-5-trifluoromethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2'-fluoro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-methyl-4-pyrazin-2-yl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2,6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6-methyl-2'-trifluoromethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2'-cyano-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6'-cyano-6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 2'-chloro-5'-fluoro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 5,6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Cyanomethyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Deformity-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Cyano-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carbon is acid;
(4-Methoxymethyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Deformity-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Cyano-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Cyclopentyl-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Cyano-thiazol-2-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-methoxymethyl-thiazol-2-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methylcarbamoyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyrimidine-2-carboxylic acid;
(4-Methoxymethyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methoxymethyl-thiazol-2-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(4-Methoxymethyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methoxymethyl-thiazol-2-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(5-Methyl-thiazol-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(4-Methoxymethyl-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Cyanomethyl-thiazol-2-yl)-amide 5-fluoro-6'-IU the Il-[3,4']bipyridinyl-2'-carboxylic acid and
(5-fluoro-thiazol-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid.

6. Compounds according to claim 1 of formula (IB):

where Y, Z, R2, R3, R5and R7are as defined in claim 1 or 3.

7. Compounds according to claim 6 of the formula (1B), where they are selected from the group consisting of:
(2-Methyl-thiazol-4-yl)-amide 4-(3,5-dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(3,4-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 6-(3,5-debtor-phenyl)-2-methyl-pyrimidine-4-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 5-methoxy-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(4-fluoro-3-trifluoromethyl-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-TIA the ol-4-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 2'-chloro-3,6-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(3,5-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 5-fluoro-3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 3,6-dimethyl-4-pyrimidine-5-yl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(2-Methyl-thiazol-4-yl)-amide 4-(3,4-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid and
(2-Methyl-thiazol-4-yl)-amide 2'-fluoro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid.

8. Compounds according to claim 1 of formula (IB):

where Y, Z, R2, R3and R6are as defined in claim 1 or 3.

9. The compound of claim 8 of formula (IB), where they are selected from the group consisting of:
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3,5-dichloro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3,4-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-IU the Il-1H-pyrazole-3-yl)-amide 6-(3,5-debtor-phenyl)-2-methyl-pyrimidine-4-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 5-methoxy-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(4-fluoro-3-trifluoromethyl-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3,5-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 3,6-dimethyl-4-pyrimidine-5-yl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3,4-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 5-fluoro-3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 2'-chloro-3,6-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide ,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 6,2',6'-trimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 2'-chloro-5'-fluoro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 5,6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 6,2',5'-trimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 6'-cyano-6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 2'-cyano-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(1-Methyl-1H-pyrazole-3-yl)-amide 6-methyl-4-pyrimidine-5-yl-pyridine-2-carboxylic acid; and
(1-Methyl-1H-pyrazole-3-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyrimidine-2-carboxylic acid.

10. Compounds according to claim 1 of formula (Iك):

where Y, Z, R2, R3and R5are as defined in claim 1 or 3.

11. The compound of claim 10 of formula (Iك), where they are selected from the group consisting of:
(2-Methyl-pyrimidine-4-yl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyrimidine-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyrimidine-4-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyrimidine-4-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(4-Chloro-pyrimidine-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-chlorine is-pyrimidine-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyrimidine-4-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid and
(2-Methyl-pyrimidine-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyrimidine-2-carboxylic acid.

12. Compounds according to claim 1 of formula (Ia):

where Y, Z, R2, R3, R5and R7are as defined in claim 1 or 3.

13. The connection section 12 of the formula (Ia), where they are selected from the group consisting of:
(6-Methyl-pyridine-2-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(6-Chloro-pyridine-2-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 5-fluoro-3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 3',6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-3,6-dimethyl-pyridine-2-carboxylic acid;
(5-Cyano-pyridine-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(5-Methyl-pyridine-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(5-Chloro-pyridine-2-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(6-Methyl-pyridine-2-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(5-Chloro-feast of the DIN-2-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid and
(5-Methyl-pyridine-2-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid.

14. Compounds according to claim 1 of formula (Ie):

where Y, Z, R2, R3and R5are as defined in claim 1 or 3.

15. Connection 14 of the formula (Ie), where they are selected from the group consisting of:
(3-Chloro-phenyl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(3-Cyano-phenyl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(3-Cyano-phenyl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(3-Cyano-phenyl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(3-Cyano-phenyl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(3-Chloro-phenyl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid and Phenylamide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid.

16. Compounds according to claim 1 of formula (If):

where Y, Z, R2, R3and R5are as defined in claim 1 or 3.

17. Compounds according to article 16 of the formula (1G), where they are selected from the group consisting of:
(2-Methyl-pyridin-4-yl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 4-(4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 6-(3,5-debtor-phenyl)-2-methyl-pyrimidine-4-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 6-(3,5-debtor-phenyl)-methyl-pyrimidine-4-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 4-(3,4-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 4-(3,4-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 5-cyano-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(5-Chloro-pyridine-2-yl)-amide 4-(2,5-dimethyl-2H-pyrazole-3-yl)-6-methyl-pyridine-2-carboxylic acid;
(5-Chloro-pyridine-2-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(5-Chloro-pyridine-2-yl)-amide 4-(3-chloro-4-fluoro-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(5-Chloro-pyridine-2-yl)-amide 6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 2'-cyano-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Methyl-is iridin-4-yl)-amide 6'-cyano-6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 6'-cyano-6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 2'-cyano-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 6,2'-dimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 6,2',6'-trimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 5,6'-dimethyl-[3,4']bipyridinyl-2'-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 2'-chloro-6-methyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 6,2',5'-trimethyl-[4,4']bipyridinyl-2-carboxylic acid;
(2-Cyano-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(2-Chloro-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyrimidine-2-carboxylic acid;
(2-Methyl-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyrimidine-2-carboxylic acid and
(2-Cyano-pyridin-4-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyrimidine-2-carboxylic acid.

18. Compounds according to claim 1 of formula (Z):

where Y, Z, R2and R3are as defined in claim 1 or 3.

19. Connection p formula (1Z), where it represents a pyridine-3-alamid-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid is you.

20. Compounds according to claim 1 of formula (AI):

where Y, Z, R2, R3and R5are as defined in claim 1 or 3.

21. Compounds according to claim 20, of formula (AI), where it represents (4-fluoro-phenyl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid.

22. Compounds selected from the group consisting of:
Methyl ester 2-{[4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carbonyl]-amino}-thiazole-4-carboxylic acid;
Ethyl ester of (3-{[4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carbonyl]-amino}-pyrazole-1-yl)-acetic acid;
[1-(2,2,2-Cryptor-ethyl)-1H-pyrazole-3-yl]-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Carbamoylmethyl-1H-pyrazole-3-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid;
(1-Cyanomethyl-1H-pyrazole-3-yl)-amide 4-(3,5-debtor-phenyl)-6-methyl-pyridine-2-carboxylic acid and
(4-Fluoro-phenyl)-amide 5-fluoro-6'-methyl-[3,4']bipyridinyl-2'-carboxylic acid.

23. Drug, possessing properties of antagonists mGluR5a receptors containing as an active ingredient one or more compounds according to any one of claims 1 to 22, and pharmaceutically acceptable excipients.

24. The compound according to any one of claims 1 to 22, as well as its pharmaceutically acceptable salt for the preparation of a medicinal product having the properties of antagonists mGluR5a receptors.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: disclosed compounds have activity and selectivity towards the GABA A receptor subunit α5. In formula I , R1 denotes hydrogen, halogen, phenyl, a 6-member heterocycyl with 2 heteroatoms selected from N, O, a 5-member heteroaryl with 1-2 heteroatoms selected from S, N, cyano, lower alkyl, -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl or -(CH2)n-OH; equals 0, 1 or 2; R denotes hydrogen or lower alkyl; R2 denotes C3-C7-cycloalkyl, phenyl, 5-6-member heteroaryl with 1 heteroatom selected from N, S or a 9-10-member bicyclic heteroaryl with 1-3 heteroatoms selected from N, which are possibly substituted with one or more substitutes selected from a group comprising halogen, cyano, nitro, oxo group, lower alkyl, lower alkyl substituted with a halogen, lower alkoxy, lower alkoxy substituted with a halogen, -C(O)O-lower alkyl, lower alkylsulphonyl, -NRaRb, -C(O)-NRaRb, -C(O)-(6-member heterocyclyl with 2 heteroatoms selected from N, O), benzyloxy, 6-member heterocyclyl with 1-2 heteroatoms selected from N, S, O, possibly substituted with hydroxy, 1-2 oxo-groups, halogen or lower alkyl, or selected from a 5-6-member heteroaryl with 1-3 heteroatoms selected from N, possibly substituted with lower alkyl; Ra and Rb independently denote hydrogen, lower alkylsulphonyl, -C(O)H, -(CH2)n-N(R)2, -(CH2)n-O-lower alkyl, -(CH2)n-S-lower alkyl, -(CH2)n-S(O)2-lower alkyl, (5-member heteroaryl with 1 heteroatom selected from S)-sulphonyl, lower alkyl, -(CH2)n-(5-6-member heterocyclyl with 1 heteroatom selected from O, N), possibly substituted with lower alkyl, oxo group, or denotes -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(5-6-member heteroaryl with 1-2 heteroatoms selected from N), possibly substituted with an oxo group, -(CH2)n-OH, -(CO)-R', where R' denotes C3-C7-cycloalkyl, a 5-member heteroaryl with 1 heteroatom selected from S, or lower alkyl; R' denotes a phenyl or a 6-member heteroaryl with 1 heteroatom selected from N which are possibly substituted with a halogen or lower alkyl, optionally substituted with a halogen. The invention also relates to a medicinal agent containing one or more compounds of formula I and use of the disclosed compounds to prepare a medicinal agent.

EFFECT: high effectiveness of derivatives.

16 cl, 145 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R3 has any

of the formulae , where R1 is selected from

,

where each R2 independently denotes hydrogen, halogen, C1-C8alkyl, C1-C8alkoxy- C1-C8alkyl, C1-C8alkoxy; R4 denotes a five- or six-member monocyclic ring system, having two heteroatoms selected from O, N and S, such as pyrazinyl, isoxazole or thiazolyl, each of which can be optionally substituted with one or more of the following substitutes: C1-C8alkyl or C1-C8alkoxy; R5 and R6 independently denote hydrogen or C1-C8alkyl; R7 and R8 together form a cyclopentyl ring; R9 independently denotes C1-C8alkyl; R9a independently denotes C1-C8alkylcarbonyl or phenylcarbonyl; R10 denotes hydrogen; R11 independently denotes C1-C8alkyl or C1-C8alkoxy; R12 denotes hydrogen or -COOR17; R13 independently denotes hydrogen, phenyl and a 6-member heteroaryl containing one heteroatom selected from N; R17 denotes hydrogen; R23 denotes (a) C1-C8alkyl, phenyl, a 5-member heteroaryl containing 1-2 heteroatoms selected from S and N, where any phenyl or heteroaryl residue is optionally substituted with a halogen, C1-C8alkyl or C1-C8alkoxy; R24 denotes C1-C8alkyl; R27 denotes H, C1-C8alkyl, C1-C8alkoxy, O-phenyl, S-phenyl; R29 denotes -(CH2)w-COOR17; where w=0; R31 denotes hydrogen; and pharmaceutically acceptable salts thereof. The invention also relates to a method of producing the disclosed compounds, a pharmaceutical composition, having dual acting ATI and ETA receptor antagonist properties, containing the disclosed compound as an active component, use of the compound in preparing a medicinal agent and methods of treating arterial hypertension.

EFFECT: high effectiveness of the compounds.

8 cl, 1 dwg, 39 ex

FIELD: chemistry.

SUBSTANCE: compound of formula (I) has antiviral activity toward the human cytomegalovirus (HCMV) or some other representative of the Herpes virida group. In formula (I)

, R1 is a group of formula , where * denotes the point of bonding to a carbonyl group, R3 denotes a pyridyl which can be substituted with a substitute independently selected from a group comprising C1-C6alkyl or a cyano group, R5 and R6 independently denote hydrogen, R2 denotes a phenyl which can be substituted with a substitute selected from a group comprising a trifluoromethoxy group, a difluoromethoxy group and a monofluoromethoxy group, A is a group of formula

or , where * denotes the point of bonding to the carbonyl group, # denotes the point of bonding to the nitrogen atom of urea, R7 denotes C1-C6alkyl which can be substituted with a substitute selected from a group comprising C3-C6cycloalkyl, R8 and R9 independently denote hydrogen, halogen or C1-C6alkyl. The invention also relates to a method of producing a compound of formula (I) from a compound of formula , a method of producing a compound of formula (V), a medicinal agent containing the disclosed compound, use of the compound in preparing a medicinal agent and a method of fighting viral infections, among them human cytomegalovirus (HCMV) or some other representative of the Herpes viridae group.

EFFECT: high antiviral activity.

9 cl, 1 tbl, 39 ex

FIELD: chemistry.

SUBSTANCE: formula (I) compound has antibacterial activity and can be used as a medicinal agent. In formula ,

R1 is hydrogen, halogen, C1-4alkyl; R2 is selected from hydrogen, halogen, C1-4alkyl; R3 is selected from hydrogen, halogen, cyano, C1-4alkyl; W is -N(R6)-; X is a single bond; ring A is an unsaturated or partially saturated ring containing 5-6 atoms, one or two of which are independently selected from nitrogen and sulphur; or an unsaturated or partially saturated bicyclic ring containing 9-10 atoms, one, two or three of which are selected from nitrogen and sulphur; R4 and R5 are substitutes on a carbon atom and are independently selected from a halogen, nitro, cyano, hydroxy, amino, carboxy, carbamoyl, formyl, hydroxy iminomethyl, C1-4alkoxyminomethyl, C1-4alkyl, C1-4alkoxy, C1-4alkanoyl, C1-4alkoxy)carbamoyl, N-(C1-4alkyl)-N-(C1-4alkoxy)carbamoyl, C1-4alkylS(O)a, where a equals 0-2, C1-4alkoxycarbonyl, C1-4alkoxycarbonylamino, C1-4alkylsulphonylamino, (saturated or unsaturated carbocycle containing 3-7 atoms)-R10- or (saturated, partially saturated or unsaturated ring containing 5-6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R11-; where R4 and R5 can independently and optionally substituted at the carbon atom with one or more R12; R6 is hydrogen; n equals 1-4; where values of R4 can be identical or different; m equals 0-4; where values of R5 can be identical or different; R12 is selected from azido, halogen, cyano, hydroxy, amino, carboxy, C1-4alkyl, C2-4alkenyl, C2-4alkynyl, C1-4alkoxy, C1-4alkanoyl, N-(C1-4alkyl)amino, N,N-(C1-4alkyl)2amino, C1-4alkylS(O)a, where a equals 0-2, (saturated or unsaturated cabocycle containing 3-7 atoms)-R14- or (saturated, partially saturated or unsaturated ring containing 5 or 6 atoms, one or two of which are selected from nitrogen, oxygen and sulphur)-R15-; where R12 can independently and optionally be substituted at the carbon atom with one or more R9; R10, R11, R14 and R15 are independently selected from a single bond, -C(O)-, -N(R19)C(O)- or -C(O)N(R20)-; where R19 and R20 are independently selected from hydrogen or C1-4alkyl; R16 is selected from halogen, cyano, hydroxy, carboxy, methyl and methoxy. The invention also relates to a pharmaceutical composition, having antibacterial activity, containing the disclosed compound as an active ingredient, use of the disclosed compound to prepare a medicinal agent and a method of producing the compound of formula (I).

EFFECT: high activity of the compounds.

22 cl, 52 tbl, 721 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention describes compounds of formula I: formula I or its pharmaceutically acceptable salt, where the radical values R3, R4, R2, X1, X2, R1 are such as presented in claim 1. Also, the invention describes a pharmaceutical composition exhibiting a Tec-family kinase inhibitor activity and based on the compounds of formula I, a method of Tec-family kinase activity inhibition, and a method of producing the compound of formula I.

EFFECT: produced and described new compounds which are effective as Tec-family (eg, Tec, Btk, Itk/Emt/Tsk, Bmx, Txk/Rlk) protein kinase inhibitors, and acceptable compositions are applicable for treatment or prevention of some diseases, disorders or conditions including but not limited, autoimmune, inflammatory, proliferative or hyperproliferative, or immunologically mediated diseases.

50 cl, 18 ex, 3 tbl

FIELD: medicine.

SUBSTANCE: in formula (I) , the ring A represents 6-members aryl or 5-6-members heteroaryl containing 1-2 heteroatoms selected from nitrogen and sulphur; Q means C3-8 cycloalkyl, 5-6-members heterocycle containing 1 heteroatom selected from oxygen, nitrogen or sulphur, C1-6 alkyl or C2-6 alkenyl; the ring T represents 5, 6, 9 or 10-members heteroaryl or 9-members heterocycle optionally additionally substituted by 1-3 heteroatoms independently selected from nitrogen or sulphur. The values of other substitutes are specified in the patent claim. Also, the invention refers to methods for preparing oxime derivatives of general formula (I), to pharmaceutical compositions containing the compound of the invention as an active ingredient and to applications of the compounds of the invention in preparing a drug.

EFFECT: compounds of the invention exhibit properties of a glucokinase activator.

33 cl, 1499 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula (I): where: A is a monocyclic or polycyclic aryl or heteroaryl group, where the heteroaryl radical denotes a 5-10-member cyclic system containing at least one heteroaromatic ring and containing at least one heteroatom selected from O, S and N; optionally substituted with one or more substitutes independently selected from a group comprising halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, C1-4alkoxy and a hydroxyl group; B is a monocyclic nitrogen-containing heteroaryl group, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from S and N; optionally substituted with one or more substitutes selected from a group consisting of halogen atoms, C1-4alkyl, C3-8cycloalkyl, C3-8cycloalkyl-C1-4alkyl, aryl and C1-8alkylthio; either a) R1 is a group of formula: -L-(CR'R")n-G, where L is a binding group selected from a group consisting of a direct bond, -(CO)-, -(CO)NR'- and -SO2-; R' and R" is independently selected from hydrogen atoms; n assumes values from 0 to 1; and G is selected from a group consisting of a hydrogen atom and C1-4alkyl, aryl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O, S and N; C3-8cycloalkyl and saturated heterocyclic groups, where heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one or two carbon atoms are substituted with a N heteroatom; where alkyl, C3-8cycloalkyl, aryl or heteroaryl groups are unsubstituted or substituted with one or more substitutes selected from halogen atoms; and R2 is a group selected from hydrogen atoms, halogen atoms and C1-4alkyl, C2-5alkynyl, C1-4alkoxy, -NH2 and cyano groups, where alkyl and alkynyl groups may be unsubstituted or substituted with one aryl group; or b) R2, R1 and -NH- group to which R1 is bonded form a group selected from groups of formulae and , where: Ra is selected from a hydrogen atom or groups selected from C1-4alkyl, C3-8cycloalkyl, aryl, aryl-C1-4alkyl, heteroaryl, where the heteroaryl radical denotes a 5-6-member heteroaromatic ring containing at least one heteroatom selected from O and N; saturated heterocyclic rings, where the heterocyclic group denotes a non-aromatic saturated 6-member carbocyclic ring in which one carbon atom is substituted with a heteroatom selected from O and N; and C1-4alkylthio; where the aryl or heteroaryl groups are unsubstituted or substituted with one or more groups selected from halogen atoms, cyano group, trifluoromethoxy and carbamoyl; Rb denotes hydrogen; and pharmaceutically acceptable salts thereof and N-oxides; provided that the compound is not selected from N-[6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]benzamide, and N-[3-ethoxycarbonyl-6-(1-methyl-1H-indol-3-yl)-5-pyridin-2-ylpyrazin-2-yl]formamide. The invention also relates to a pharmaceutical composition, use of compounds in any of claims 1-20, a method of treating a subject, as well as a composite product.

EFFECT: obtaining novel biologically active compounds having adenosine A2B receptor antagonist activity.

27 cl, 160 ex, 2 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to novel substituted 2-quinolyloxazoles of formula (I) or pharmaceutically acceptable salts thereof, having PDE4 inhibiting properties, a pharmaceutical composition based on said compounds and use thereof to prepare a medicinal agent which inhibits inflammatory cell recruitment in respiratory tracts. , where is , X is O, R1 is alkyl, R3 and R4 are independently selected from H, R5 and R6 are independently selected from a group comprising H, alkyl, hydroxyalkyl, t equals 1 or 2. Values of substitutes R7-R11, R13 are given in the formula of invention.

EFFECT: high efficiency of using the composition.

24 cl, 1 dwg, 64 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to oxazolidinone derivatives covered by general graphic formula (I) and to their pharmaceutically acceptable salts. In formula (I) R1, R2, R3 and R4 are independently chosen from a group including -H and halogen; A is chosen from a group including R5 and R6 are independently chosen from a group including -H, -F, -CI, -Br, -OH, alkyl(C1-C6), haloalkyl(C1-C6), alkoxygroup(C1-C6); R7 is chosen from a group including -H, alkyl(C1-C6); either R7 and R5 or R6 taken together form a cycle of 2 carbon atoms and include 1 group chosen from O which in turn can be substituted by one substitute chosen from alkyl(C1-C6); R12 is chosen from a group including -H, -COR14, -CSR14, -COOR14; R14 is chosen from a group including alkyl (C1-C6), cycloalkyl(C3-C6), alkenyl(C2-C6), R16, R17 and R18 represent -H; R21 is chosen from a group including -H, alkyl(C1-C6); X is chosen from a group including O, S, and Y is chosen from a group including O, S, SO, SO2, and NR12; and optional substitutes of alkyl(C1-C6) groups can represent one or two groups chosen from the following: -OR21, -CN.

EFFECT: invention refers to methods for preparing the compounds of the invention, to application of oxazolidinone derivatives for preparing a drug for treating bacterial infections and to a pharmaceutical composition for treating bacterial infections, including a therapeutically effective amount of the compound of the invention.

36 cl, 10 tbl, 44 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel imidazole derivatives of general formula I and pharmaceutically acceptable salts thereof, where R1 is selected from a group comprising aryl and alkyl, optionally substituted hydroxy; R2 is selected from a group comprising hydrogen and alkyl; R3 is selected from a group comprising hydrogen and -X-A, where X is selected from a group comprising -C(O)- and -S(O)2-; and A is selected from a group comprising hydrogen, optionally substituted alkyl, optionally substituted alkoxy, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocycle and optionally substituted cycloalkyl, where the optionally substituted groups are substituted with 1-2 substitutes selected from a group comprising alkyl, substituted alkyl, alkoxy, substituted amine which is a -NRR group, substituted aryloxy, heteroaryl, heterocycle, halogen, hydroxy and -S(O)2-R9, where R9 is an alkyl; or R1 and R3 together with a carbon atom bonded to R1 and a nitrogen atom bonded to R3 form a heterocyclic or substituted heterocyclic group; R4 is selected from a group comprising hydrogen, linear alkyl, -alkylene-aminoacyl-, -alkylene-hydroxy-, -[alkylene]p-nitrogen-containing heterocycle, -[alkylene]p-nitrogen-containing substituted heterocycle, -[alkylene]p-nitrogen-containing heteroaryl, -[alkylene]p-nitrogen-containing substituted heteroaryl and -[alkylene]p-NR10R11, where p equals 0 or 1, the alkylene contains 1-5 carbon atoms and can have 1 or 2 substitutes selected from a group comprising amine, hydroxy and halogen, aminoacyl relates to a group -C(O)NRR, where each R is independently selected from a group comprising hydrogen and alkyl, R10 and R11 are independently selected from a group comprising hydrogen, alkyl, substituted alkyl, -S(O)2-alkyl, substituted aryl, substituted heteroaryl, cycloalkyl, or when R10 is hydrogen, R11 is hydroxy, alkoxy or substituted alkoxy; or when R1 and R3 together with carbon and nitrogen atoms respectively bonded to them do not form a heterocyclic or a substituted heterocyclic group, R3 and R4 together with a nitrogen atom to which they are bonded form a spiro-condensed heterocyclic group; R5 is selected from a group comprising L-A1, where L is selected from a group comprising C1-C5alkylene, where the alkylene is defined above; and A1 is selected from a group comprising aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycle; and one of R6 or R7 is selected from a group comprising aryl and heteroaryl, each of which can optionally be substituted with -(R8)m, where m equals a whole number from 1 to 2, and the other of R6 or R7 is selected from a group comprising hydrogen, halogen and alkyl; or R6 as well as R7 denotes hydrogen; R8 is selected from a group comprising cyano, alkyl, -CF3, alkoxy, halogen, where alkyl, aryl, aryloxy, cycloalkyl, heterocycle, heteraryl and substituted alkyl, aryl, aryloxy, cycloalkyl, heterocycle and heteroaryl are described in claim 1. The invention also relates to specific compounds, a pharmaceutical composition based on the compound of formula I, a method of inhibiting KSP and use of the composition to prepare a medicinal agent.

EFFECT: novel imidazole derivatives are useful as kinesin spindle protein inhibitors for treating cancer.

25 cl, 27 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel compounds of formula as well as separate enantiomers, diastereomers, racemic mixures and pharmaceutically acceptable salts thereof, having mitotic kinesin KSP inhibiting activity, as well as inhibitory action on tumour cells, use thereof in preparing a medicinal agent and a pharmaceutical composition based on said compounds. In said formula, R denotes Z-NR2R3, Z-OH, Ar1 and Ar2 independently denote a phenyl which, if needed, is substituted with one or more groups independently selected from: F, CI, Br, I, OH, Z denotes an alkylene having 1-6 carbon atoms which, if needed, is substituted with C1-6alkyl, and R1 assumes values given in the claim.

EFFECT: improved method.

16 cl, 3 dwg, 124 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new compounds of formula (I) and to their pharmaceutically acceptable salts exhibiting P2X3 receptor antagonist activity. In formula (I), X represents -O-; Y represents -NRdRe where one of radicals Rd and Re means hydrogen, and the other means hydrogen; C1-C12alkyl; C5-C7cycloalkyl; C5-C7cycloalky-C1-C12alkyl; hydroxy-C1-C12alkyl; acetyl; aminocarbonyloxy- C1-C12alkyl or heterocyclyl representing a 6-members saturated ring containing heteroatom S substituted by two oxo groups; D represents optional oxygen; R1 represents isopropyl; R2 represents hydrogen; R5 represents hydrogen or C1-C12alkyl; R4 means hydrogen; C1-C12alkyl; halogen; halogen- C1-C12alkyl; C1-C12alkoxy; hydroxy; halogen- C1-C12alkoxy; nitro; amino; hydroxy- C1-C12alkyl; C1-C12alkoxyalkyl; hydroxy- C1-C12alkoxy; C1-C12alkylsulphonyl; cyano; heteroaryl representing a 5-members aromatic ring containing one, two or three heteroatoms selected from O, S and N which can be optionally substituted by a thio group, C1-C12alkyl or C1-C12alkylsulphonyl; heterocyclyl representing a 6-members saturated ring containing two heteroatoms N, one of which is substituted C1-C12alkylsulphonyl; -(CH2)m-(Z)n-(CO)-Rf or -(CH2)m-(Z)n-SO2-(NRg)n-Rf where each m and n independently represents 0 or 1, Z means NR8, Rf means C1-C12alkyl, hydroxy, amino or hydroxy- C1-C12alkyl, and Rg means hydrogen; R3 represents methoxy; R6 represents hydrogen; and one of radicals R7 and R8 represents hydrogen, and the other represents hydrogen, acetyl or phenyl.

EFFECT: also, the invention refers to a pharmaceutical composition and to an application of the compound of formula (I) for preparing a drug.

8 cl, 3 tbl, 70 ex

FIELD: medicine.

SUBSTANCE: in formula (I) , the ring A represents 6-members aryl or 5-6-members heteroaryl containing 1-2 heteroatoms selected from nitrogen and sulphur; Q means C3-8 cycloalkyl, 5-6-members heterocycle containing 1 heteroatom selected from oxygen, nitrogen or sulphur, C1-6 alkyl or C2-6 alkenyl; the ring T represents 5, 6, 9 or 10-members heteroaryl or 9-members heterocycle optionally additionally substituted by 1-3 heteroatoms independently selected from nitrogen or sulphur. The values of other substitutes are specified in the patent claim. Also, the invention refers to methods for preparing oxime derivatives of general formula (I), to pharmaceutical compositions containing the compound of the invention as an active ingredient and to applications of the compounds of the invention in preparing a drug.

EFFECT: compounds of the invention exhibit properties of a glucokinase activator.

33 cl, 1499 ex

FIELD: medicine.

SUBSTANCE: compounds can be used for treating neurological conditions, more specifically for treating neurodegenerative conditions, such as Alzheimer's disease. In a compound of formula I R2 represents H or CH2NR1R4 where R1 and R4 are independently selected from H, unsubstituted C1-6alkyl, substituted or unsubstituted C3-6 cycloalkyl, R3 represents H; substituted or unsubstituted C1-4alkyl; substituted or unsubstituted C2-4alkenyl; substituted or unsubstituted 6-members aryl condensed or uncondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl, containing 1-2 nitrogen atoms in a cycle; substituted or unsubstituted saturated or unsaturated 5 or 6-members N-containing heterocycle which can additionally contain nitrogen, oxygen or the sulphur atom condensed or ucondensed with substituted or unsubstituted 6-members aryl or 5-6-members heteroaryl containing nitrogen in a cycle; (CH2)nR6 where n is an integer from 1 to 6, and the values of R6 and the values of other radicals are specified in the patent claim.

EFFECT: increased antiamyloidogenic action.

20 cl, 20 tbl, 6 dwg, 7 ex

FIELD: medicine.

SUBSTANCE: invention refers to chemical-pharmaceutical industry, and concerns a EP2 agonist which exhibits the EP3 agonist action, and induce a neurotising and/or protective effect and thereby is effective as a therapeutic agent for a peripheral nerve disease, such as lower and upper motor neuron disorder, nerve root disease, plexopathy, brachial plexus compression syndrome, peripheral neuropathy, neurofibromatosis and nervomuscular conduction disease.

EFFECT: EP2 agonist which exhibits the EP3 agonist action; it is a safe and effective neurotisation and/or protection agent which has an insignificant impact on the cardiovascular system.

13 cl, 36 ex, 1 tbl

FIELD: chemistry.

SUBSTANCE: present invention relates to hot or sweet flavourants in form of a synthetic amide compound or edible salt thereof in amount ranging from approximately 0.001 parts per million to approximately 100 parts per million. The amide compound has formula

where A is a phenyl or a 5- or 6-member heteroaryl ring selected from a group comprising pyridine, pyrazine, pyrazole, thiazole, furan, thiophene, benzofuran and benzothiophene; m equals 1, 2 or 3, each R1 is independently selected from hydroxyl, fluorine, chlorine, SEt, SCH3, methyl, ethyl, isopropyl, vinyl, trifluoromethyl, methoxy, ethoxy and isopropoxy, or alternatively two R1 are bonded to form a saturated C1-C3 alkylenedioxy ring on the phenyl; and R2 is a C3-C10 branched alkyl. The amide compound also has formula

in which substitutes A, B, R50, R60, R70, R80, n and m assume values given in the formula of invention. The amide compound is also a specific chemical compound.

EFFECT: obtaining hot and sweet taste modifiers and boosters for food and medicinal products.

39 cl, 7 tbl, 180 ex

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 a compound of formula (I) or pharmaceutically acceptable salts thereof, where Q is CH or N; R2 is C1-C4 alkyl or C3-C4-cycloalkyl; Y is R5-O; where R5 is propynyl; X is selected from a group consisting of aryl, heteroaryl, C1-C5-alkyloxy, heterocycloalkyl, arylamino, heteroarylamino, heteroaryl-C1-C4-alkylamino, aryloxy, aryl-C1-C2-alkyloxy or C3-C6-cycloalkyl-C1-C4-alkyloxy, each of which is optionally substituted with 1-3 times; the optional substitute(s) for X is(are) independently selected from a group comprising halogen, cyano, trifluoromethyl, nitro, hydroxy, C1-C4-alkyl, C1-C4-alkoxy, C1-C4-alkyloxy-C1-C4-alkoxy, -SMe, SO2-C1-C2-alkyl, -NMe2, - C(O)O-C1-C5-alkyl, -SCF3, -SO2-NH2, -SO2-C2-alkyl-OH, -CONH2, -COMe, - CONH-C1-C4-alkyl, -CONMe2, -NHCOMe, -CH2COOEt, -OCH2COOEt, -CH2- cyclopropyl, and each R3 and R4 is H; where aryl denotes phenyl or naphthyl; heteroaryl denotes monocyclic or bicyclic hydrocarbon containing 5-10 ring atoms, one or more of which are heteroatoms selected from O, N or S; heterocyclyl denotes piperidinyl or benzodioxolyl; or a compound or pharmaceutically acceptable salt thereof, selected from a group comprising (4-dimethylaminophenyl)-[4-(4-cyclopropylphenyl)-6-propargyloxyquinazolin-2-yl]methanone, (3-sulphamoylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, [3-(2-hydroxyethanesulphonyl)phenyl]amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methylsulphanylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, (3-methanesulphonylphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4-dihydroquinazoline-2-carboxylic acid, and (5-ethanesulphonyl-2-hydroxyphenyl)amide 4-(4-isopropylphenyl)-6-prop-2-ynyloxy-3,4- dihydroquinazoline -2-carboxylic acid. The invention also relates to a pharmaceutical composition based on the compound of formula (I) and use of the compound of formula (I).

EFFECT: novel benzoquinazoline derivatives, which are useful in treating bone disorders, are obtained.

6 cl, 128 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to new cyclopenta[b]benzofuranyl derivatives of formula wherein substitutes R1, R2, R3, R4, R5, R6 and R7 and n are specified in the patent clam. These compounds exhibit properties of NF-kB-activity and/or AP-1 inhibitor/modulator. Also, the inventive subject matter are methods for preparing intermediate compounds thereof, a pharmaceutical composition containing them, administration thereof for prevention and/or treatment of inflammatory and autoimmune diseases, neurodegenerative diseases and hyperproliferative diseases caused by NF-kB- and/or AP-1-activity, and a method for prevention and/or treatment of said diseases.

EFFECT: preparation of new cyclopenta[b]benzofuranyl derivatives.

21 cl, 3 tbl, 151 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula I or tautomer thereof or pharmaceutically acceptable salts thereof, where R2 is C1-3-alkyl or cyclopropyl; R9 is a halogen, C1-3-alkyl, -O-(C1-3-alkyl), -S-(C1-3alkyl) or CF3 and p equals 1-2. The disclosed compounds are Aurora protein kinase inhibitors. Said compounds can be used in a method of inhibiting Aurora protein kinase activity. The invention also discloses pharmaceutically acceptable compositions containing such compounds; and a method of treating proliferative disorders in a patient using said compounds.

EFFECT: more effective use of the compounds.

11 cl, 7 tbl, 20 ex

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