Diarylcycloalkyl derivatives, processes for their preparation and their use as pharmceuticals
View Patent ↗Diarylcycloalkyl derivatives and their physiologically acceptable salts and physiologically functional derivatives are disclosed. The compounds include those of formula I, in which the radicals are as defined, and their physiologically acceptable salts and processes for their preparation. The compounds typically have lipid- and/or triglyceride-lowering properties and are suitable, for example, for the treatment of disorders of lipid metabolism, of type II diabetes, and of syndrome X.
1. A compound of formula I
in which
Ring A is (C 3 -C 8 )-cycloalkyl;
R1, R2, R4, R5, independently of one another, are H, F, CI, Br, OH, NO 2 , CN, CF 3 , OCF 3 , (C 1 -C 6 )-alkyl or O—(C 1 -C 6 )-alkyl;
R 3 is H or (C 1 -C 6 )-alkyl;
X is (C 1 -C 2 )-alkyl where, in the alkyl group, one carbon atom is replaced by an oxygen atom; and
Y is (C 1 -C 2 )-alkyl where, in the alkyl group, one carbon atom is replaced by an oxygen atom;
or a physiologically acceptable salt of a compound of formula I.
2. A compound as claimed in claim 1 , wherein
Ring A is cyclohexyl;
R1, R2, R4, R5 are, independently of one another, H, F, Cl, Br, OH, NO 2 , CN, CF 3 , OCF 3 , (C 1 -C 3 )-alkyl or O—(C 1 -C 3 )-alkyl; and
R3 is H or (C 1 -C 3 )-alkyl.
3. A compound as claimed in claim 2 , wherein
R1, R2, R4, R5 are, independently of one another, H, CF 3 , OCF 3 , (C 1 -C 3 )-alkyl or O—(C 1 -C 3 )-alkyl; and
R3 is H or CH 3 .
4. A compound as claimed in claim 3 , wherein
R1 is H, CF 3 , OCF 3 , (C 1 -C 3 )-alkyl or O—(C 1 -C 3 )-alkyl;
R2, R3, R4 are, independently of one another, H or (C 1 -C 3 )-alkyl; and
R5 is H or CH 3 .
5. A compound as claimed in claim 4 , wherein
R1 is CF 3 , OCF 3 , OCH 3 ; or (C 1 -C 3 )-alkyl;
R2, R3 are, independently of one another, H or CH 3 ;
R4 is (C 1 -C 3 )-alkyl; and
R5 is H or CH 3 .
6. A compound as claimed in claim 5 , wherein
R1 is CF 3 , or OCF 3
R4 is CH 3 ; and
R5 is CH 3 .
7. A compound as claimed in claim 5 , wherein
R1 is OCH 3 ; or (C 1 -C 3 )-alkyl;
R4 is (C 1 -C 3 )-alkyl; and
R5 is CH 3 .
8. A compound as claimed in claim 7 , wherein
R1 is CH 3 ; and
R4 is (C 2 -C 3 )-alkyl.
9. A compound as claimed in claim 7 , wherein
R1 is OCH 3 ; and
R4 is CH 3 or C 3 -alkyl.
10. A compound as claimed in claim 7 , wherein
R1 is C 3 -alkyl; and
R4 is CH 3 .
11. A compound as claimed in claimed in claim 1 wherein the compound is chosen from:
2-Methyl-6-[(1R,3S)-3-(5-methyl-2-(4-(2-propyl)-phenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid;
2-methyl-6-[(1R,3S)-3-(5-methyl-2-(4-trifluoromethoxyphenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid;
2-methyl-6-[(1R,3S)-3-(5-methyl-2-(4-trifluoromethylphenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid;
2-[(1R,3S)-3-(2-(4-methoxy-3-methylphenyl)-5-methyl-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-6-methyl-benzoic acid;
2-methyl-6-[(1R,3S)-3-(2-(4-methylphenyl)-5-(2-propyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid;
2-[(1R,3S)-3-(2-(3-Methoxyphenyl)-5-(2-propyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-6-methyl-benzoic acid;
2-[(1R,3S)-3-(5-ethyl-2-(4-methylphenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-6-methyl benzoic acid; and
a physiologically acceptable salt thereof.
12. 2-Methyl-6-[(1R,3S)-3-(5-methyl-2-(4-(2-propyl)-phenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid or a physiologically acceptable salt thereof.
13. 2-methyl-6-[(1R,3S)-3-(5-methyl-2-(4-trifluoromethoxyphenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid or a physiologically acceptable salt thereof.
14. 2-methyl-6-[(1R,3S)-3-(5-methyl-2-(4-trifluoromethylphenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid or a physiologically acceptable salt thereof.
15. 2-[(1R,3S)-3-(2-(4-methoxy-3-methylphenyl)-5-methyl-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-6-methyl-benzoic acid or a physiologically acceptable salt thereof.
16. 2-methyl-6-[(1R,3S)-3-(2-(4-methylphenyl)-5-(2-propyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-benzoic acid or a physiologically acceptable salt thereof.
17. 2-[(1R,3S)-3-(2-(3-Methoxyphenyl)-5-(2-propyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-6-methyl-benzoic acid or a physiologically acceptable salt thereof.
18. 2-[(1R,3S)-3-(5-ethyl-2-(4-methylphenyl)-oxazol-4-ylmethoxy)-cyclohexyloxymethyl]-6-methyl benzoic acid or a physiologically acceptable salt thereof.
19. A pharmaceutical, comprising:
at least one compound as claimed in claim 1 ;
at least one further active compound; and
a pharmaceutically acceptable carrier.
20. A pharmaceutical, comprising:
at least one compound as claimed in claim 1 ;
at least one lipid- or triglyceride-lowering active compound; and
a pharmaceutically acceptable carrier.
21. A process for preparing a pharmaceutical, comprising:
mixing at least one compound as claimed in claim 1 with a pharmaceutically acceptable carrier to form a mixture; and
bringing this mixture into a form suitable for administration to form the pharmaceutical.
22. A compound of formula I
in which
Ring A is (C 3 -C 8 )-cycloalkyl; wherein, in the cycloalkyl ring, two carbon atoms may be replaced by an oxygen atom;
R1, R2, R4, R5, independently of one another, are H, F, Cl, Br, OH, NO 2 , CN, CF 3 , OCF 3 , (C 1 -C 6 )-alkyl or O—(C 1 -C 6 )-alkyl;
R3 is H or (C 1 -C 6 )-alkyl;
X is (C 1 -C 6 )-alkyl where, in the alkyl group, one carbon atom may be replaced by an oxygen atom; and
Y is (C 1 -C 6 )-alkyl where, in the alkyl group, one carbon atom may be replaced by an oxygen atom;
or a physiologically acceptable salt of a compound of formula I.
23. A compound as claimed in claim 22 , wherein
Ring A is 1,3-(C 3 -C 8 )-cycloalkandiyl;
R1, R2, R4, R5 are, independently of one another, H, F, Cl, Br, OH, NO 2 , CN, CF 3 , OCF 3 , (C 1 -C 3 )-alkyl or O—(C 1 -C 3 )-alkyl;
R3 is H or (C 1 -C 3 )-alkyl;
X is (C 1 -C 6 )-alkyl where, in the alkyl group, one carbon atom is replaced by an oxygen atom; and
Y is (C 1 -C 6 )-alkyl where, in the alkyl group, one carbon atom is replaced by an oxygen atom.
24. A compound as claimed in claim 23 , wherein
R1, R2, R4, R5 are, independently of one another, H, F, Cl, Br, OH, NO 2 , CN, CF 3 , OCF 3 , (C 1 -C 3 )-alkyl or O—(C 1 -C 3 )-alkyl;
R3 is H or CH 3 ;
X is (C 1 -C 2 )-alkyl where, in the alkyl group, one carbon atom is replaced by an oxygen atom; and
Y is (C 1 -C 2 )-alkyl where, in the alkyl group, one carbon atom is replaced by an oxygen atom.
25. A compound as claimed in claim 24 , wherein
R1 is H, CF 3 , OCF 3 , (C 1 -C 3 )-alkyl or O—(C 1 -C 3 )-alkyl;
R2, R3, R4 are, independently of one another, H or (C 1 -C 3 )-alkyl; and
R5 is CH 3 .
26. A compound as claimed in claim 25 , wherein
Ring A is 1,3-cyclohexandiyl;
R1 is CF 3 , OCF 3 , OCH 3 ; or (C 1 -C 3 )-alkyl;
R2, R3 are, independently of one another, H or CH 3 ;
R4 is (C 1 -C 3 )-alkyl; and
R5 is CH 3 .
27. A compound as claimed in claim 22 , wherein
X is —CH 2 —O—; and
Y is —O—CH 2 —.
28. A compound as claimed in claim 24 , wherein
R2 and R3 are H.
29. A compound as claimed in claim 22 , wherein
R1 is in the 3- or 4-position.
30. A compound as claimed in claim 22 , wherein
—COOR3 is in the 1-position and R5 is in the 2-position.
31. A pharmaceutical, comprising:
at least one compound as claimed in claim 22 ;
at least one further active compound; and
a pharmaceutically acceptable carrier.
32. A pharmaceutical, comprising:
at least one compound as claimed in claim 22 ;
at least one lipid- or triglyceride-lowering active compound; and
a pharmaceutically acceptable carrier.
33. A process for preparing a pharmaceutical, comprising:
mixing at least one compound as claimed in claim 22 with a pharmaceutically acceptable carrier to form a mixture; and
bringing this mixture into a form suitable for administration to form the pharmaceutical.