Annelated N-heterocyclic sulfonamides with oxadiazolone headgroup, processes for their preparation and their use as pharmaceuticals
Annelated N-heterocyclic sulfonamides with oxadiazolone headgroup, processes for their preparation and their use as pharmaceuticals The invention relates to annelated N-heterocyclic sulfonamides with oxadiazolone headgroup and to their physiologically acceptable salts and physiologically functional derivatives showing PPARdelta or PPARdelta and PPARalpha agonist activity. What is described are compounds of the formula I, in which the radicals are as defined, and their physiologically acceptable salts and processes for their preparations. The compounds are suitable for the treatment and/or prevention of disorders of fatty acid metabolism and glucose utilization disorders as well as of disorders in which insulin resistance is involved and demyelinating and other neurodegenerative disorders of the central and peripheral nervous system.
1. Compound of the formula I:
wherein
Y is O;
R1 is H, halogen, (C1-C8)alkyl, (C0-C4)alkylene-(C3-C7)cycloalkyl, (C0-C4)alkylene-(C5-C10)heteroaryl, (C0-C4)alkylene-O—(C0-C8)alkyl, (C0-C4)alkylene-(C6-C10)aryl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R2 is H, (C1-C8)alkyl, halogen, (C0-C4)alkylene-O—(C0-C8)alkyl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R5 is H, (C1-C8)alkyl, (C0-C4)alkylene-(C3-C7)cycloalkyl, (C0-C4)alkylene-(C6-C10)aryl, (C0-C4)alkylene-(C5-C10)heteroaryl, (C0-C4) alkylene-N(R10)(R11), wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R6 is H, (C1-C8)alkyl, (C0-C4)alkylene-(C3-C7)cycloalkyl, (C0-C4)alkylene-(C6-C10)aryl, (C0-C4)alkylene-(C5-C10)heteroaryl, (C0-C4)alkylene-N(R10)(R11), wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R7 is H, halogen, (C1-C8)alkyl, (C0-C4)alkylene-O—(C0-C4)alkylene-H, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R8 is H, halogen, (C1-C8)alkyl, (C0-C4)alkylene-O—(C0-C4)alkylene-H, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F, whereby R8 is only attached to carbon;
R9 is H, halogen, (C1-C8)alkyl, (C0-C4)alkylene-(C3-C7)cycloalkyl, (C0-C4)alkylene-O—(C0-C8)alkyl, (C0-C4)alkylene-(C6-C10)aryl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R10 is H, (C1-C8)alkyl, (C0-C4)alkylene-O—(C0-C8)alkyl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F;
R11 is H, (C1-C8)alkyl, (C0-C4)alkylene-O—(C0-C8)alkyl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F; and
X 1 , X 2 , X 3 , X 4 and X 5 are CH;
in all its stereoisomeric forms and mixtures in any ratio, or its physiologically acceptable salts and tautomeric forms.
2. Compound of the formula I, as claimed in claim 1 , wherein Y is O; R1 is H, halogen, (C1-C8)alkyl, (C0-C4)alkylene-(C3-C7) cycloalkyl, (C0-C4)alkylene-(C5-C10)heteroaryl, (C0-C4)alkylene-O—(C0-C8)alkyl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substitued by F;
R2 is H, (C1-C8)alkyl, halogen;
R5 is H, (C1-C8)alkyl;
R6 is H, (C1-C8)alkyl;
R7 is H, halogen, (C1-C8)alkyl;
R8 is H, halogen, (C1-C8)alkyl;
R9 is H, halogen, (C1-C8)alkyl, (C0-C4)alkylene-O—(C0-C8)alkyl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substitued by F;
R10 is H, (C1-C8)alkyl;
R11 is H, (C1-C8)alkyl; and
X 1 , X 2 , X 3 , X 4 , and X 5 are CH.
3. Compound of the formula I, as claimed in claim 1 , wherein
R1 is F, Cl, (C1-C4)alkyl, (C0-C2)alkylene-(C3-C6)cycloalkyl, (C0-C2)alkylene-(C5-C6)heteroaryl, (C0-C2)alkylene-O—(C1-C6)alkyl, wherein alkyl and alkylene are unsubstituted or 1- to 3-fold substituted by F.
4. Compound of the formula I, as claimed in claim 1 , wherein
R2 is in the para position to R1.
5. Compound of the formula I, as claimed in claim 1 , wherein
R2 is H, (C1-C3)alkyl, F, Cl.
6. Compound of the formula I, as claimed in claim 1 , wherein
R5 is H, (C1-C4)alkyl.
7. Compound of the formula I, as claimed in claim 1 , wherein
R6 is H, (C1-C4)alkyl.
8. Compound of the formula I, as claimed in claim 1 , wherein
R7 is H, F, Cl, (C1-C4)alkyl.
9. Compound of the formula I, as claimed in claim 1 , wherein
R8 is H, F.
10. Compound of the formula I, as claimed in claim 1 , wherein
R9 is H, Cl, (C1-C8)alkyl, O—(C1-C4)alkyl, wherein alkyl is unsubstituted or 1- to 3-fold substituted by F.
11. Compound of the formula I, as claimed in claim 1 , wherein
R10 is H.
12. Compound of the formula I, as claimed in claim 1 , wherein
R11 is H.
13. Compound of the formula I, as claimed in claim 1 , wherein
Y is, 0;
R1 is H, F, Cl, (C1-C4)alkyl, O—(C1-C4)alkyl, (C3)cycloalkyl, (C5)heteroaryl, wherein alkyl is unsubstituted or 1- to 3-fold substituted by F;
R2 is H, Cl;
R5 is H, (C1-C4)alkyl;
R6 is H, (C1-C4)alkyl;
R7 is H;
R8 is H;
R9 is CF 3 ; and
R10 is H.
14. A pharmaceutical composition comprising one or more compounds of the formula I as claimed in claim 1 and a pharmaceutically acceptable carrier therefor.
15. A process for preparing a pharmaceutical comprising one or more of the compounds as claimed in claim 1 , which comprises mixing the active compound with a pharmaceutically suitable carrier and bringing this mixture into a form suitable for administration.
16. A method for the treatment of type-2 diabetes which comprises administering to a patient in need thereof a compound of formula I according to claim 1 .
17. A method for the treatment of dyslipidemia which comprises administering to a patient in need thereof a compound of formula I according to claim 1 .