Aryl-isoxazole-4-yl-imidazole derivatives

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to aryl-isoxazole-4-yl-imidazole derivatives of formula I and to their pharmaceutically acceptable acid addition salts. The compounds of the present invention exhibit GABA A α5 receptor binding site activity and selectivity. In general formula I

each of R1-R3 independently represents hydrogen atom or halogen atom; R4 represents hydrogen atom, lower alkyl, C3-C7cycloalkyl, -(CH2)n-O-lower alkyl or hydroxy substituted lowest alkyl; R5 represents -(CH2)m-phenyl or -(CH2)m-(5-6-members heteroaryl with 1-2 heteroatoms independently seected from N, O) which optionally substituted by one or more substitutes selected from a group consisting of halogen atom, cyano, nitro, lower alkyl, lower alkoxy, lower alkylsulphanyl, lower alkyl substituted by halogen atom, -C(O)-lower alkyl, -C(O)-O-lower alkyl, -NH-C(O)-O-lower alkyl or -C(O)-NH-R' where R' represents the lower alkynyl or hydroxy substituted lower alkyl, or represents -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(6-members heterocyclyl with 1-2 heteroatoms selected from N, O), -(CH2)n-(5-6-members heteroaryl with 1-2 heteroatoms selected from N, O) or -(CH2)n-phenyl optionally substituted by halogen atom; R6 represents hydrogen atom, -C(O)H, -(CH2)n-O-lower alkyl, -C(O)O-lower alkyl, lower alkyl substituted by hydroxy or halogen atom, or represents C3-C7-cycloalkyl, phenyl, or represents -(CH2)n-O-CH2-phenyl optionally substituted by halogen atom or lower alkyl, or represents -(CH2)n-O-CH2-(6-members heteroaryl with 1 heteroatom selected from N) optionally substituted by lower alkyl or lower alkyl substituted by halogen atoms, or represents -(CH2)n-NH-(CH2)o-(6-members heterocyclyl with 2 heteroatoms selected from N; n means 0, 1, 2 or 3; m means 0 or 1; o means 1, 2 or 3.

EFFECT: presented preparation of a drug containing one or more compound of formula I and application of the compounds for preparing the drug.

31 cl, 168 ex

 

The text descriptions are given in facsimile form.

1. Aryl-isoxazol-4-yl-imidazole derivatives of formula I:

where each of R1-R3independently represents a hydrogen atom by Iliuta halogen;
R4represents a hydrogen atom, lower alkyl, C3-C7-cycloalkyl, -(CH2)n-O-lower alkyl or lower alkyl substituted hydroxy;
R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which may be substituted by one or more than one Deputy, selected from the group consisting of halogen atom, cyano, nitro, lower alkyl, lower alkoxy, lower alkylsulfanyl, lower alkyl substituted by halogen atom,
-C(O)-lower alkyl, -C(O)-O-lower alkyl, -NH-C(O)-O-lower alkyl or-C(O)-NH-R', where
R' represents a lower quinil or lower alkyl, substituted hydroxy, or represents -(CH2)n-C3-C7-cycloalkyl, -(CH2)n-(6-membered heterocyclyl with 1-2 heteroatoms, selected from N, O), -(CH2)n-(5-6-membered heteroaryl with 1-2 heteroatoms, selected from N, O) or -(CH2)n-phenyl, possibly substituted by a halogen atom;
R6represents a hydrogen atom, -C(O)H, -(CH2)n-O-lower alkyl, -C(O)O-lower alkyl, lower alkyl, substituted hydroxy or halogen atom, or represents a C3-C7-cycloalkyl, phenyl, or represents
-(CH2)n-O-CH2-phenyl, possibly substituted the first atom of halogen or lower alkyl, or is a
-(CH2)n-O-CH2-(6-membered heteroaryl with one heteroatom selected from N), possibly substituted lower alkyl or lower alkyl substituted by halogen atoms, or represents
-(CH2)n-NH-(CH2)about-(6-membered heterocyclyl 2 heteroatoms selected from N, O);
n is 0, 1, 2 or 3;
m is 0 or 1;
o is 1, 2 or 3, as well as their pharmaceutically acceptable salts accession acids.

2. The compound of formula I according to claim 1, where
each of R1-R3independently represents a hydrogen atom or a halogen atom;
R4represents a hydrogen atom or lower alkyl;
R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), possibly substituted by one or more than one halogen atom, cyano, nitro, lower alkyl, lower alkoxy, lower alkylsulfanyl, lower alkyl substituted by halogen atom, -(CO)-lower alkyl, -(CO)-O-lower alkyl, -NH-(CO)-O-lower alkyl;
R6represents a hydrogen atom, a C3-C7-cycloalkyl, phenyl, or lower alkyl;
m is 0 or 1;
and their pharmaceutically acceptable salts accession acids.

3. Aryl-isoxazol-4-yl-imidazole of proizvoditeli I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is not substituted.

4. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 3, selected from the group consisting of
5-methyl-3-phenyl-4-(1-phenyl-1H-imidazol-4-yl)-isoxazol,
2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-pyridine,
2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-pyridine,
2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-pyrimidine,
4-(1-benzyl-1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazol,
2-{4-[3-(2-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyrimidine,
2-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyrimidine,
2-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyrimidine,
2-{4-[3-(4-bromo-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyrimidine,
4-(1-benzyl-1H-imidazol-4-yl)-3-(4-bromo-phenyl)-5-methyl-isoxazol,
2-{4-[3-(3,4-debtor-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyrimidine,
2-[2-methyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-pyrimidine,
2-[2-benzoyloxymethyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-pyrimidine,
4-(1-benzyl-2-benzoyloxymethyl-1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazol,
4-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyridine,
3-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-pyridi is a,
[3-phenyl-4-(1-phenyl-1H-imidazol-4-yl)-isoxazol-5-yl]-methanol,
4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-phenyl-1H-imidazole-2-carboxylic acid methyl ester or
4-(2-benzoyloxymethyl-1-phenyl-1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazol.

5. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by one or more than one halogen atom.

6. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 5, selected from the group consisting of:
4-[1-(4-fluoro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3-fluoro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3-chloro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(4-bromo-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3-bromo-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3,4-debtor-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3,5-debtor-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3-chloro-4-fluoro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(3,4-dichloro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(2,4-dichloro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(2-fluoro-5-methoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(4-fluoro-shall ensil)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(2-chloro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(2-bromo-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
3-(4-fluoro-phenyl)-4-[1-(4-fluoro-phenyl)-1H-imidazol-4-yl]-5-methyl-isoxazol,
4-[1-(4-bromo-phenyl)-1H-imidazol-4-yl]-3-(4-fluoro-phenyl)-5-methyl-isoxazol,
3-(4-fluoro-phenyl)-4-[1-(3-fluoro-phenyl)-1H-imidazol-4-yl]-5-methyl-isoxazol,
4-[1-(3-chloro-phenyl)-1H-imidazol-4-yl]-3-(4-fluoro-phenyl)-5-methyl-isoxazol,
4-[1-(3-bromo-phenyl)-1H-imidazol-4-yl]-3-(4-fluoro-phenyl)-5-methyl-isoxazol,
4-[1-(3,4-debtor-phenyl)-1H-imidazol-4-yl]-3-(4-fluoro-phenyl)-5-methyl-isoxazol,
4-[1-(3,5-debtor-phenyl)-1H-imidazol-4-yl]-3-(4-fluoro-phenyl)-5-methyl-isoxazol or
4-[1-(3,5-dichloro-phenyl)-1H-imidazol-4-yl]-3-(4-fluoro-phenyl)-5-methyl-isoxazol.

7. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by one or more cyano.

8. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 7, selected from the group consisting of:
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzonitrile,
3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzonitrile,
4-[2-benzoyloxymethyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzonitrile,
4-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzo is itril,
3-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzonitrile or
4-[4-(5-hydroxymethyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzonitrile.

9. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by nitro.

10. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 9, selected from the group consisting of:
5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol,
3-(2-fluoro-phenyl)-5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
3-(3-fluoro-phenyl)-5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
3-(3-bromo-phenyl)-5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
3-(4-fluoro-phenyl)-5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
3-(4-bromo-phenyl)-5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
3-(3,4-debtor-phenyl)-5-methyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
5-methyl-4-[2-methyl-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol,
4-[2-benzoyloxymethyl-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
5-methyl-4-[1-(3-nitro-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol,
3-(4-fluoro-phenyl)-5-methyl-4-[1-(4-methyl-3-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol,
5-ethyl-3-(4-fluoro-phenyl)-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-from whom sasala,
5-cyclopropyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol,
[4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1H-imidazol-2-yl]-methanol,
4-[2-chloromethyl-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1H-imidazole-2-carbaldehyde,
5-methyl-4-[2-(4-methyl-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol,
4-[2-(4-fluoro-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[2-(4-chloro-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[2-(4-bromo-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[2-(3-chloro-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[2-(3-fluoro-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[2-(3-bromo-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[2-(2-fluoro-benzoyloxymethyl)-1-(4-nitro-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1H-imidazol-2-ileocecal]-pyridine,
2-methyl-6-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1H-imidazol-2-ileocecal]-pyridine,
3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1H-imidazol-2-ileocecal]-pyridine,
5-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1 is-imidazol-2-ileocecal]-2-trifluoromethyl-pyridine or
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-nitro-phenyl)-1H-imidazol-2-ileocecal]-pyridine,
5-ethyl-4-[1-(4-nitro-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol.

11. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which substituted lower alkyl.

12. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 11, selected from the group consisting of:
5-methyl-3-phenyl-4-(1-meta-tolyl-1H-imidazol-4-yl)-isoxazol,
5-methyl-3-phenyl-4-[1-(4-propyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
4-[2-benzoyloxymethyl-1-(5-methyl-isoxazol-3-ylmethyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
5-methyl-4-[1-(5-methyl-isoxazol-3-ylmethyl)-2-phenyl-1H-imidazol-4-yl]-3-phenyl-isoxazol,
3-(4-fluoro-phenyl)-5-methyl-4-(1-meta-tolyl-1H-imidazol-4-yl)-isoxazol or
3-(4-fluoro-phenyl)-5-methyl-4-[1-(4-methyl-3-nitro-phenyl)-1H-imidazol-4-yl]-isoxazol.

13. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by lower alkoxy.

14. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to item 13, selected from the group consisting of:
4-[1-(4-meth is XI-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(4-ethoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(2-ethoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
4-[1-(2-fluoro-5-methoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
3-(2-fluoro-phenyl)-4-[1-(4-methoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-isoxazol,
3-(3-fluoro-phenyl)-4-[1-(4-methoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-isoxazol or
4-[1-(3-ethoxy-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol.

15. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which substituted lower alkylsulfanyl.

16. Aryl-isoxazol-4-yl-imidazole derivative of formula I according to § 15, where this derivative is a 5-methyl-4-[1-(4-methylsulfanyl-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol.

17. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by lower alkyl, substituted by a halogen atom.

18. Aryl-isoxazol-4-yl-imidazole derivatives of formula I in 17 selected from the group consisting of:
5-methyl-3-phenyl-4-[1-(3-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
5-methyl-3-FeNi is-4-[1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
5-methyl-3-phenyl-4-[1-(2-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
4-[1-(3,5-bis-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
3-(3,4-debtor-phenyl)-5-methyl-4-[1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
5-methyl-4-[2-methyl-1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-3-phenyl-isoxazol,
4-[2-benzoyloxymethyl-1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-5-methyl-3-phenyl-isoxazol,
3-(4-fluoro-phenyl)-5-methyl-4-[1-(3-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
3-(4-fluoro-phenyl)-5-methyl-4-[1-(2-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
5-ethyl-3-(4-fluoro-phenyl)-4-[1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol,
{3-phenyl-4-[1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol-5-yl}-methanol,
{3-(4-fluoro-phenyl)-4-[1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol-5-yl}-methanol,
3-(4-fluoro-phenyl)-5-methoxymethyl-4-[1-(4-trifluoromethyl-phenyl)-1H-imidazol-4-yl]-isoxazol or
4-(5-methyl-3-phenyl-isoxazol-4-yl)-1-(4-trifluoromethyl-phenyl)-1H-imidazole-2-carboxylic acid ethyl ester.

19. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by -(CO)-lower alkyl.

20. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 19, selected from the group, with the standing of:
1-{4-[4-(3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-ethanone,
1-{4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-ethanone,
1-{4-[4-(5-ethyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-ethanone,
1-(4-{4-[3-(2-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-(4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-(4-{4-[3-(3-bromo-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-(4-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-(4-{4-[3-(4-bromo-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-(4-{4-[3-(3,4-debtor-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-{4-[2-methyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-ethanone,
1-{4-[2-benzoyloxymethyl-4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-ethanone,
1-(4-{4-[5-ethyl-3-(4-fluoro-phenyl)-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone,
1-{4-[4-(5-cyclopropyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-ethanone,
1-(4-{4-[3-(4-fluoro-phenyl)-5-hydroxymethyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone or
1-(4-{4-[3-(4-fluoro-phenyl)-5-methoxymethyl-isoxazol-4-yl]-imidazol-1-yl}-phenyl)-ethanone.

21. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), to the which is substituted by -(CO)-O-lower alkyl.

22. Aryl-isoxazol-4-yl-imidazole derivative of formula I according to item 21, where this derivative is a
3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzoic acid methyl ester,
4-{5-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzoic acid ethyl ester or
4-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzoic acid methyl ester.

23. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by-NH-(CO)-O-lower alkyl.

24. Aryl-isoxazol-4-yl-imidazole derivative of formula I according to item 23, where this derivative is a
{4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-phenyl}-carbamino acid tert-butyl ether.

25. Aryl-isoxazol-4-yl-imidazole derivatives of the formula I according to claim 1, where R5represents -(CH2)m-phenyl, or -(CH2)m-(5-6-membered heteroaryl with 1-2 heteroatoms, independently selected from N, O), which is substituted by-C(O)-NH-R', where R' represents a lower quinil or lower alkyl, substituted hydroxy, or represents -(CH2)n-C3-C7-cycloalkyl,
-(CH2)n-(6-membered heterocyclyl with 1-2 heteroatoms, selected the data from N, O),
-(CH2)n-(5-6-membered heteroaryl with 1-2 heteroatoms, selected from N, O) or
-(CH2)n-phenyl, possibly substituted by a halogen atom.

26. Aryl-isoxazol-4-yl-imidazole derivative of formula I according A.25, where these compounds are:
N-cyclopropylmethyl-4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-prop-2-inyl-benzamid,
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-(3-morpholine-4-yl-propyl)-benzamide,
N-cyclopropyl-4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclobutyl-4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclopentyl-4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-(tetrahydro-Piran-4-yl)-benzamid,
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-pyridin-3-ylmethyl-benzamide,
4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-pyridin-4-ylmethyl-benzamide,
N-(3-fluoro-phenyl)-4-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclopropylmethyl-3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclopropyl-3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclobutyl-3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclopentyl-3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide
3-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-(tetrahydro-Piran-4-yl)-benzamid,
N-cyclopropylmethyl-2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-prop-2-inyl-benzamid,
N-cyclobutyl-2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
N-cyclopentyl-2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-benzamide,
2-[4-(5-methyl-3-phenyl-isoxazol-4-yl)-imidazol-1-yl]-N-(tetrahydro-Piran-4-yl)-benzamid,
N-cyclopropylmethyl-4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-prop-2-inyl-benzamid,
N-cyclopropyl-4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
N-cyclobutyl-4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
N-cyclopentyl-4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-(2-hydroxy-ethyl)-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-(2-morpholine-4-yl-ethyl)-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-(3-morpholine-4-yl-propyl)-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-[2-(1H-imidazol-4-yl)-ethyl]-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-furan-2-ylmethyl-benzamide,
4-{4-[3-(3-fluoro-phenyl)-5-methyl-and oxazol-4-yl]-imidazol-1-yl}-N-pyridin-2-ylmethyl-benzamide,
N-(3-fluoro-phenyl)-4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
N-cyclopropylmethyl-3-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
N-cyclopropyl-3-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
N-cyclobutyl-3-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
N-cyclopentyl-3-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide,
3-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-(tetrahydro-Piran-4-yl)-benzamide;
4-{4-[3-(3-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-N-pyridin-3-ylmethyl-benzamide or
N-cyclopentyl-4-{4-[3-(4-fluoro-phenyl)-5-methyl-isoxazol-4-yl]-imidazol-1-yl}-benzamide.

27. Drug having activity and selectivity towards the sites of binding of GABA And α5 receptor containing one or more than one compound of formula I according to any one of claims 1 to 26, and pharmaceutically acceptable excipients.

28. Drug in item 27 for the treatment of diseases related to GABA And the α5 subunit selected from a cognitive disorder, or suitable as a cognitive amplifier.

29. Drug for p for the treatment of Alzheimer's disease.

30. The use of the compounds of formula I according to any one of claims 1 to 26 for the preparation of drugs having activity and selectivity about what to wear to the binding sites of GABA And α5 receptor.

31. The application of article 30 of the compounds of formula I according to claim 1 in the preparation of drugs for treatment of Alzheimer's disease.



 

Same patents:

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula

, where the dotted line in the 6-member nitrogen-containing ring Z of formula (I) (said ring Z consists of ring atoms numbered 1 to 6) indicates that a double bond is either present in the 3,4-position of the ring Z of formula (I), or a double bond is absent in ring Z of formula (I); and where the double bond may be present in the 3,4-position of the ring Z of formula (I); or: the double may be absent in ring Z of formula (I) if: i) X denotes N or N+-O-, or ii) V denotes -O-CH2-Q-, or iii) W denotes para-substituted phenyl or para-substituted pyridinyl, and V denotes pyrrolidinyl of formula:

X denotes CH, N, or N+-O-; W denotes para-substituted phenyl or para-substituted pyridinyl; V denotes -O-CH2-Q-, where Q is bonded with a group U of formula (I), or V denotes pyrrolidinyl of formula:

U denotes mono-, di-, tri- or tetra-substituted aryl, where the substitutes are independently selected from C1-7-alkyl and halogen; Q denotes a five-member heteroaryl with two or three heteroatoms independently selected from O and N; R1 denotes C1-7-alkyl or cycloalky; R2 denotes halogen or C1-7-alkyl; R3 denotes halogen or hydrogen; R4 denotes C1-7-alkyl-O-(CH2)0-4-CH2-; R'R"N-(CH2)0-4-CH2-, where R' and R" are independently selected from a group consisting of hydrogen, C1-7-alkyl (optionally substituted with one-three fluorine atoms), cyclopropyl (optionally substituted with one-three fluorine atoms), cyclopropyl- C1-7-alkyl (optionally substituted with one-three fluorine atoms) and -C(=O)-R"', where R'" denotes C1-4-alkyl, C1-4-alkoxy, -CH2-CF3, or cyclopropyl; or R12NH-C(=O)·(O)0-1-(CH2)0-4-, where R12 denotes C1-4-alkyl or cyclopropyl; and n equals 0; and salts thereof. The invention also relates to a pharmaceutical composition.

EFFECT: obtaining novel biologically active compounds having inhibiting effect on renin.

21 cl, 112 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of formula

,

where R1 is a phenyl group (said phenyl group is substituted with one or more C1-6alkyl groups, one C1-3alkyl group (said C1-3alkyl group is substituted with one or more halogen atoms), one C1-3alkoxy group (said C1-3alkoxy group is substituted with one or more halogen atoms) or one or more halogen atoms), R2 is a C1-3alkyl group, R3 is a phenyl group (said phenyl group is substituted with one or more substitutes selected from a group comprising halogen atoms or a (C=O)R5' group (where R5' is NR6'R7', (where R6' is a hydrogen atom, and R7' is a C1-6alkyl group substituted with a hydroxyl group))), a thienyl group (said thienyl group is substituted with one or more substitutes selected from a group comprising hydrogen atoms and a (C=O)R5 group (where R5 is NR6R7 (where R6 is a hydrogen atom or a C1-3alkyl group, and R7 is a C1-6alkyl group (said C1-6alkyl group can be substituted with one or more hydroxyl groups, one C1-3alkoxy group or a 5-6-member aromatic heterocyclic group containing 1-2 heteroatoms selected from oxygen or nitrogen (where the 5-6-member aromatic heterocyclic group can be substituted with one or more C1-3alkyl groups, one or more C1-3alkoxy groups, and in case of a 5-6-member aromatic heterocyclic group containing one nitrogen atom, can be in be in form of N-oxides)), a pyridyl group, or overall NR6R7 is a nitrogen-containing heterocyclic group which is a 5-6-member hetero-monocyclic group which contains one or two nitrogen atoms and can additionally contain on oxygen atom (said nitrogen-containing heterocyclic group can be substituted with one or more hydrogen atoms, one or more C1-6alkyl group, one or more hydroxyl groups)) or C1-6alkyl group (said C1-6alkyl group can be substituted with one or more halogen atoms and is substituted with one cyano group))), and R4 is a hydrogen atom or to a pharmaceutically acceptable salt of said compound. The invention also relates to a medicinal agent for preventing or treating diseases, in which activation of the thrombopoietin receptor is effective, based on said compounds.

EFFECT: obtaining novel compounds and agents based thereon, which can be used in medicine to increase the number of thrombocytes.

33 cl, 7 tbl, 43 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted oxazole derivatives of general formula I. The disclosed compounds have affinity to the µ-opioid receptor. In general formula I

, n equals 0, 1 or 2, R1 denotes a phenyl residue bonded through a C1-C3alkyl chain, R2 denotes phenyl or thienyl, each of which is unsubstituted or mono-substituted with F or Cl, R3 and R4 independently denote a saturated, branched or straight C1-C6alkyl, phenyl or a phenyl residue bonded through a C1-C3akyl chain, or R3 and R4 together form an unsubstituted five-, six- or seven-member saturated ring which can optionally contain an extra heteroatom selected from a group comprising O or NR9, where R9 denotes phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which is unsubstituted or mono-substituted with a substitute selected from a group comprising F, Cl, Br, I and O-C1-C6alkyl, where the ring can be optionally condensed with a phenyl ring, R5 and R6 independently denote a saturated, branched or straight C1-C6alkyl, R7 and R8 independently denote a saturated, branched or straight unsubstituted C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, or R7 and R8 together form an unsubstituted or mono- or disubstituted five-, six- or seven-member saturated ring, where the substitutes are selected from a group comprising C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, where the ring can optionally contain an extra heteroatom selected from a group comprising S, O and NR10, where R10 denotes a phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which can be unsubstituted or mono-substituted with O-C1-C6alkyl. The invention also relates to methods of producing the disclosed compounds, a medicinal agent containing at least one substituted oxazole derivative of formula I, use of the compounds to prepare a medicinal agent.

EFFECT: improved properties.

13 cl, 1 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: present invention refers to a compound of formula I ; or to its pharmaceutically acceptable salts where n represents 0, 1 or 2; Y1 represents a bond or a group C(O); Y2, represents a bond, the groups C(O) or S(O)2; R1 represents hydrogen, halogen, cyano, C1-2alkyl; R2 represents hydrogen, halogen, cyano, C1-4alkyl, C1-3alkoxy, halogen-substituted-C1-3alkyl, halogen-substituted-C1-3alkoxyl, C6aryl-C0alkyl, tetrazolyl, C3-6cycloalkyl-C0alkyl, C6-7heterocycloalkyl-C0-4alkyl where 1 or 2 carbon atoms in the ring are substituted by the groups selected from -O-, -NH-, -S(O) and -SO2-; and phenoxy groups; where said aryl and heterocycloalkyl groups R2 can be substituted by 1 or 2 radicals independently selected from C1-6alkyl; R3 represents hydrogen, halogen, cyano, C1-3alkoxy or halogen-substituted-C1-2alkyl group and a group -NR6aR6b where R6a and R6b are independently selected from hydrogen and C1-4alkyl; R4 represents hydrogen, halogen, cyano, C1-3alkoxy or halogen-substituted-C1-2alkyl group; R5 represents hydrogen or C1-3alkyl group; L represents a bivalent radical selected from ; ; ; ; ; ; ; ; ; ; ; ; and ; where asterisks the junctions of Y2 and R2; where any bivalent radical L can be substituted by 1 or 2 radicals independently selected from halogen, hydroxy, cyano, C1-4alkyl, C1-4alkyl carbonylamino, C1-4alkoxy, C1-4alkoxycarbonyl, halogen-substituted - C1-4alkyl, C1-3alkylsulfonyl, C1-3alkylsulfonyl-amino, cyano-substituted - C1-4alkyl and halogen-substituted -C1-4alkoxy radicals. Also, the invention refers to a method of Hedgehog path inhibition in a cell and to a method of undesired cell proliferation inhibition which involves the interaction of the compound of formula I and the cell.

EFFECT: new substituted imidazole derivatives which can be effective in treatment of some types of cancer are prepared.

13 cl, 1 tbl, 3 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel oxadiazole compounds of formula (1) and pharmaceutically acceptable salts thereof, where R1 and R2 assume values given in the description, Y is a single bond. The invention also relates to use of said compounds as DGAT1 inhibitors, for example for treating obesity and diabetes, and a method of inhibiting.

EFFECT: high treatment efficiency.

13 cl, 65 tbl, 712 ex

FIELD: chemistry.

SUBSTANCE: invention relates to a compound having structure

, radicals are as described in the formula of invention, as well as pharmaceutically-acceptable salt, prodrug, tautomer and stereoisomer thereof. The invention also relates to a composition, a set for modulating PPAR based on said compound, a method of treating a patient suffering from a disease or condition or at risk of a disease or condition, for which PPAR modulation is therapeutically useful.

EFFECT: novel compounds which are active towards PPAR are obtained and described.

41 cl, 622 ex, 8 tbl

FIELD: chemistry.

SUBSTANCE: invention relates to a method of producing 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one derivatives of general formula 1, , where 1a R=Br, R'=CH2OCH3, R"=CH3; 1b R=H, R'=CH2, R"=CH3; 1c R=H, R1=CH2OCH3, R"=Ph; 1d R=H, R'=CH3, R"=Ph; 1e R=Br, R=CH3, R" - fur-2-yl, which can be used as potential biologically active substances and intermediate products for synthesis of novel heterocyclic systems. The method of producing 3 -(2-substituted-1,3 -oxazol-4-yl)pyridin-2( 1 H)-ones of general formula I involves formation of a heterocyclic system of 3-(1,3-oxazol-4-yl)pyridin-2(1H)-one as a result of base-catalysed regrouping of 3-acylamino-2-furfurylfuro[2,3-b]pyridines while boiling said compounds in ethanol for 4-20 hours with addition of 6-7 mmol of potassium hydroxide per 1 mol of the initial 3-acylamino-2-furfurylfuro[2,3-b]pyridine.

EFFECT: high yield.

1 cl, 2 tbl, 5 ex

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 compounds of formula (I) or pharmaceutically acceptable salts, solvates or tautomers thereof, where substitute M is selected from groups D1 and D2, having structural formulae given below, and R1, E, A and X are as described in the formula of invention. Disclosed also are pharmaceutical compositions which contain these compounds, methods for synthesis of these compounds, intermediate compounds and synthesis methods thereof, as well as use of compounds of formula (I) in preventing or treating diseases mediated by CDK kinases, GSK-3 kinases or Aurora kinases.

EFFECT: high effectiveness of the compounds.

40 cl, 8 dwg, 18 tbl, 84 ex

FIELD: chemistry.

SUBSTANCE: invention relates to substituted oxazole derivatives of general formula I. The disclosed compounds have affinity to the µ-opioid receptor. In general formula I

, n equals 0, 1 or 2, R1 denotes a phenyl residue bonded through a C1-C3alkyl chain, R2 denotes phenyl or thienyl, each of which is unsubstituted or mono-substituted with F or Cl, R3 and R4 independently denote a saturated, branched or straight C1-C6alkyl, phenyl or a phenyl residue bonded through a C1-C3akyl chain, or R3 and R4 together form an unsubstituted five-, six- or seven-member saturated ring which can optionally contain an extra heteroatom selected from a group comprising O or NR9, where R9 denotes phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which is unsubstituted or mono-substituted with a substitute selected from a group comprising F, Cl, Br, I and O-C1-C6alkyl, where the ring can be optionally condensed with a phenyl ring, R5 and R6 independently denote a saturated, branched or straight C1-C6alkyl, R7 and R8 independently denote a saturated, branched or straight unsubstituted C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, or R7 and R8 together form an unsubstituted or mono- or disubstituted five-, six- or seven-member saturated ring, where the substitutes are selected from a group comprising C1-C6alkyl or a phenyl residue bonded through a C1-C3alkyl chain, where the ring can optionally contain an extra heteroatom selected from a group comprising S, O and NR10, where R10 denotes a phenyl or a phenyl residue bonded through a C1-C3alkyl chain, any of which can be unsubstituted or mono-substituted with O-C1-C6alkyl. The invention also relates to methods of producing the disclosed compounds, a medicinal agent containing at least one substituted oxazole derivative of formula I, use of the compounds to prepare a medicinal agent.

EFFECT: improved properties.

13 cl, 1 tbl, 150 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention refers to a compound of formula (I) in which A means a group of formula or in which * specifies a carbon atom binding site of a pyridinyl ring, and # specifies the a carbon atom binding site of a phenyl ring, R1 means an amino group or a methyl-carbonylamino group, R2 means hydrogen, R3 means hydrogen, R4 means hydrogen, R5 means hydrogen or halogen, R6 means hydrogen or halogen, R7 means hydrogen, R8 means hydrogen, or one of its salts, its solvate or solvate of its salts, to a method of preparing it, to an agent for treatment and/or prevention of viral infections, on the basis of this compound. Also, the invention refers to the application of the compound of formula I for preparing the agent and to the method of viral infection control.

EFFECT: new arylsulfonamides which can are effective as antiviral agents, preferentially for cytomegalovirus control are prepared and described.

9 cl, 5 ex, 2 tbl, 1 dwg

FIELD: medicine.

SUBSTANCE: invention refers to a compound of formula , where R1 represents aryl, heteroaryl or (C5-C6)-cycloalkyl, each of which has an optional substitute halogen or (C1-C6)-alkyl; R2 represents hydrogen or (C1-C4)-alkyl; R3 represents -P(=O)-(alkoxy)2 or Y1Y2N-SO2-, cycloalkyl, aryl, heteroaryl, heterocyclyl, cycloalkenyl, each of which has an optional substitute: halogen, hydroxy, carboxy, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2N-SO2, R7-SO2-NR6-, R7-C(=O)-NR6-, or alkyl, alkoxy, alkoxycarbonyl, each of which has an optional substitute halogen, -P(=O)-(alkoxy)2, Y1Y2NC(=O)-, Y1Y2N-SO2-, R7 -SO2-NR6 -, aryl or heteroaryl and when R3 is cycloalkyl, cycloalkenyl, heterocyclyl, it also optionally substituted by oxo; L1 represents a bond or (C1-C6)-alkylene, which is optionally substituted by -P(=O)-(alkoxy)2; R4, R5 and R6 are hydrogen, R7 represents alkyl; both Y1 and Y2 independently is hydrogen, alkyl which has an optional substitute: hydroxy, amino, alkylamino, dialkylamino, alkoxy, cycloalkyl, or Y1 and Y2 together with nitrogen atom whereto attached form heterocyclyl which optionally contains one more heteroatoms selected from oxygen, nitrogen or sulphur where heterocyclyl has an optional substitute alkyl or oxo; provided when L1 represents a bond, R3 is not optionally substituted by phenyl, optionally substituted by naphthyl, optionally substituted by benzoimidazolyl, optionally substituted by benzothiazolyl or optionally substituted by tetrazolyl; or to its pharmaceutically acceptable salt, and also to a pharmaceutical composition including a compound of formula I.

EFFECT: there are produced and described new compounds which can be effective in treating allergic or inflammatory disorders, particularly such disorders, as allergic rhinitis, asthma or chronic obstructive pulmonary disease.

25 cl, 118 ex

FIELD: chemistry.

SUBSTANCE: invention relates to compounds of formula , where R1 is a 3-7-member carbocyclic ring and n is a number ranging from 1 to 8, and the rest of the radicals are described in the claim.

EFFECT: possibility of using such compounds and compositions in therapy as metabotropic glutamate receptor modulators.

33 cl, 367 ex

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: chemistry.

SUBSTANCE: in formula (I) Cy1 is a 6-member heterocyclyl containing N as a heteroatom, a 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteroatoms selected from N, S and O, phenyl or phenyl condensed with a 5-member heterocycle containing O as a heteroatom, each optionally having 1-3 identical or different substituting Cy1 groups which are: (C1-C6)-acyl, cyano, carboxy, hydroxy, (C1-C6)alkylsulphonyl, (C3-C6)-cycloalkyl, a 6-member heterocyclyl containing 1-2 heteroatoms selected from O and N, phenyl, a 5-member heteroaryl containing 1-3 heteroatoms selected from N, S and O, Y1Y2N-, Y1Y2NC(=O)-, Y1Y2NSO2-, (C1-C6)-alkyl-SO2-N(R5)-C(=O)-, R6-C(=O)-N(R5)-, R7-NH-C(=O)-NH-; (C1-C6)-alkoxycarbonyl; (C1-C6)-alkyl, which optionally contains 1-3 identical or different substitutes which are halogen, carboxy, cyano, hydroxy, Y1Y2N-, Y1Y2N-C(=O)-, R6-C(=O)-N(R5)-, R8-SO2-N(R5)-C(=O)-, 5-member heterocyclyl, containing N as a heteroatom, 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; or (C1-C6)-alkoxycarbonyl; as well as (C1-C6)-alkoxy which optionally have 1-3 identical or different substitutes which are carboxy, (C1-C6)-alkoxycarbonyl, cyano, 3-member heterocyclyl containing O as a heteroatom, or 5-member heteroaryl containing 1-3 heteroatoms selected from N and O; where phenyl or heteroaryl fragments in the substituting Cy1 groups optionally and independently have substitutes represented by hydroxy, (C1-C6)-alkyl, (C1-C6)-alkoxy, carboxy, (C1-C6)-alkoxycarbonyl or R8-SO2-N(R5)-C(=O)-; and where cycloalkyl fragments in the substituting Cy1 groups which optionally and independently have substitutes represented by (C1-C6)-alkoxy, carboxy; Cy2 is a 9-member cycloalkenyl, phenyl, 5,6-member monocyclic or 9,10-member bicyclic heteroaryl containing 1-3 heteratoms selected from N, S and O, or phenyl condensed with a 5,6-member heterocycle containing 1-2 heteroatoms selected from N and O, each independently and optionally having 1-3 identical or different substitutes represented by (C1-C6)-alkoxy, (C1-C3)-alkyl, hydroxy, halogen, halogen-(C1-C6)-alkoxy, nitro, Y1Y2N-; L1 is an alkylene with a straight or branched chain containing 1-6 carbon atoms, optionally substituted carboxy; or L1 is -CH2-(C1-C5)halogenalkylene; L2 is a bond, -O- or -CH2-O-. Other values of radicals are given in the formula of invention.

EFFECT: novel compounds have prostaglandin D2 receptor antagonist properties, can be used in treating primarily allergic disorders such as allergic rhinitis, allergic conjunctivitis, atopic dermatitis, bronchial asthma, food allergy and other diseases.

39 cl, 1 tbl, 99 ex

FIELD: chemistry.

SUBSTANCE: invention relates to novel AMPA receptor antagonists - 1H-quinazoline-2,4-dione derivatives, selected from the group: N-(6-imidazol-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,4]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-pyrrolidin-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-azetidin-1-yl-7-nitro-2,4-dioxo-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(7-nitro-2,4-dioxo-6-[1,2,3]triazol-1-yl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide; N-(6-morpholin-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; (2,4-dioxo-6-[1,2,4]triazol-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)amide ethanesulphonic acid; N-(6-imidazol-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(2,4-dioxo-6-thiomorpholin-4-yl-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide; N-(6-[1,4]oxazepan-4-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)methanesulphonamide and N-(6-azetidin-1-yl-2,4-dioxo-7-trifluoromethyl-1,4-dihydro-2H-quinazolin-3-yl)-methanesulphonamide and physiologically acceptable salts thereof.

EFFECT: compounds can be used in treating such diseases as epilepsy and schizophrenia.

9 cl, 106 ex

FIELD: medicine, pharmaceutics.

SUBSTANCE: invention relates to compound of formula I: where Y1 and Y2 are independently selected from N and CR10, where R10 is selected from group, including hydrogen, halogen, C1-C6alkyl, halogen(C1-C6)alkyl, R1 is selected from group, including hydrogen, cyano, halogen, C1-C6alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy, dimethylamino, C1-C6alkylsulfanyl, dimethylaminoethoxy and pyperasinyl, substituted up to 2 radicals C1-C6alkyl, R2 and R5 are independently selected from group, including hydrogen, cyano, halogen, C1-C6alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy and dimethylamino, R3 and R4 are independently selected from group, including hydrogen, halogen, cyano, C1-C6alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, or R1 and R5 with phenyl, to which they are bound, form C5-C10heteroaryl, R6 and R7 are independently selected from group, including hydrogen, C1-C6alkyl, C1-C6alkoxy and halogen(C1-C6)alkyl, on condition that R6 and R7 both do not represent hydrogen, R8 is selected from group, including hydrogen, halogen, C1-C6alkyl, C1-C6alkoxy and halogen(C1-C6)alkoxy, R9 is selected from -S(O)2R11, -C(O)R11, -NR12aR12b and -R11, where R11 is selected from group, including aryl, cycloalkyl and heterocycloalkyl, R12a and R12b are independently selected from (C1-C6)alkyl and hydroxy(C1-C6)alkyl, and said aryl, heteroaryl, cycloalkyl and heterocycloalkyl in composition of R9 optionally contain as substituents from 1 to 3 radicals, independently selected from group, including (C1-C6)alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy, C6-C10aryl(C0-C4)alkyl, C5-C10heteroaryl(C0-C4)alkyl, C3-C12cycloalkyl and C3-C8heterocycloalkyl, where said arylalkyl substituent in composition of R9 optionally contains as substituents from 1 to 3 radicals, independently selected from group, including halogen, cyano, (C1-C6)alkyl, halogen(C1-C6)alkyl, C1-C6alkoxy, halogen(C1-C6)alkoxy, dimethylamino and methyl-pyperasinyl, as well as to its pharmaceutically acceptable salts, hydrates, solvates and isomers. In addition, invention relates to method of inhibiting hedgehog pathway in cell and to method of inhibiting undesirable cell proliferation, when cell contacts with compound described above.

EFFECT: obtained and described are novel compounds, which can be applied in medicine.

13 cl, 153 ex, 1 tbl

FIELD: medicine, pharmaceutics.

SUBSTANCE: claimed invention relates to compounds of general formula (I-B), where values of radicals are described in formula of invention, or to its pharmaceutically acceptable salts, which possess activity of inhibiting cholesterol ester transfer protein, due to which said compounds or salts can be used for prevention and/or treatment of arteriosclerotic diseases, hyperlipemia or dislipidemia or similar diseases.

EFFECT: obtaining pharmaceutical compositions for prevention and treatment of arteriosclerosis, as well as application of formula I-B compounds for manufacturing of medication.

15 cl, 36 tbl, 252 ex

FIELD: chemistry.

SUBSTANCE: invention relates to thiophene derivatives of formula (I):

where A denotes -CONH-CH2-, -CO-CH=CH-, -CO-CH2CH2-, -CO-CH2-O-, -CO-CH2-NH-, or ; R1 denotes hydrogen, C1-5-alkyl or C1-5-alkoxy; R2 denotes hydrogen, C1-2-alkyl, C1-5-alkoxy, trifluoromethyl or halogen, R3, R31, R32, R33, R34, R4, R5, R6, R7, k, m, n are described in claim 1. The invention also relates to a pharmaceutical composition for preventing or treating diseases and disorders associated with an activated immune system, based on said compounds and to use thereof as therapeutically active compounds for preventing or treating diseases or disorders such as graft rejection, graft versus host reaction and autoimmune syndromes.

EFFECT: improved properties of the compound.

27 cl, 2 tbl, 525 ex

FIELD: medicine.

SUBSTANCE: invention relates to field of medicine and pharmacology and deals with application of derivatives of aminospirits of formula

or their phosphate derivatives for manufacturing medication for treatment of various autoimmune diseases, such as disseminated sclerosis, peripheral nephritis, retrobulbar neuritis, amyotrophic lateral sclerosis and uveitis.

EFFECT: invention ensures high treatment efficiency.

7 cl, 2 dwg, 1 tbl, 1 ex

Up!