N-[1,3,4]-thiadiazol-2-yl-benzene sulfonamides, pharmaceutical compositions thereof and methods for their therapeutic use

1. A compound of Formula I:

wherein

n is 0, or 1;

R1 is selected from the group consisting of (C1-C6) alkyl, (C0-C6) alkylene (C3-C6) cycloalkyl, and (C0-C6) alkylene-(C6-C14) aryl, wherein the alky is unsubstituted or mono, di- or tri substituted by F;

R2 and R3 are independently selected from the group consisting of H, and (C1-C6) alkyl;

A is selected from the group consisting of (C6-C14) aryl, pyridine and thiophene;

R4 and R5 are independently selected from the group consisting of H, (C1-C6) alkyl, CN, S(O) m (C1-C6) alkyl, halogen, (C0-C6) alkylene-O—(C0-C6) alkylene-H, SCF3, and S(O)2CF3, wherein the alkyl and alkylene are unsubstituted or mono, di- or trisubstituted by F, provided that when A is (C6-C14) aryl and one of R4 and R5 is halogen or (C0-C6) alkylene-O—(C0-C6) alkylene-H, then the other one of R4 and R5 is not halogen or (C0-C6) alkylene-O—(C0-C6) alkylene-H;

R6 and R7 are independently H, (C1-C6) alkyl, or (C0-C6) alkylene-(C6-C14) aryl, wherein the alkyl is unsubstituted or mono, di- or trisubstituted by (C0-C6) alkylene-O—(C0-C6)-alkylene-H, and the aryl is unsubstituted or mono, di- or trisubstituted by halogen;

R8 and R9 are independently H, or (C1-C6) alkyl; and

m is 0, 1 or 2;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

2. The compound according to claim 1 , wherein

R1 is selected from the group consisting of (C1-C6) alkyl, (C0-C6) alkylene-(C6-C14) aryl, and (C3-C6) cycloalkyl wherein the alkyl is unsubstituted or mono-, di- or trisubstituted by F;

R2 and R3 are H;

R4 is selected from the group consisting of halogen, (C1-C4) alkyl, O—(C1-C4) alkyl, and CN, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted by F;

R5 is selected from the group consisting of H, halogen, (C1-C4) alkyl, O—(C1-C4) alkyl, and S(O)2CH3, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted by F,

provided that when A is (C6-C14) aryl and one of R4 and R5 is halogen or (C0-C6) alkylene-O—(C0-C6) alkylene-H, then the other one of R4 and R5 is not halogen or (C0-C6) alkylene-O—(C0-C6) alkylene-H; and

one of R6 and R7 is selected from the group consisting of H, (C1-C6) alkyl, and (C0-C2) alkylene-(C6-C 10) aryl, wherein the alkyl is unsubstituted or mono, di- or trisubstituted by (C0-C6) alkylene-O—(C0-C6)-alkylene-H, and the aryl is unsubstituted or mono, di- or trisubstituted by F, and the other one of R6 and R7 is H; and

R8 and R9 are H;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

3. The compound according to claim 2 , wherein

R1 is selected from the group consisting of (C1-C6) alkyl, cyclopropyl and phenyl, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted by F;

A is selected from the group consisting of phenyl, naphthalene, pyridine, and thiophene;

R4 is selected from the group consisting of F, Cl, Br, (C1-C4) alkyl, O—(C1-C4) alkyl, and CN, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted by F;

R5 is selected from the group consisting of H, F, Cl, (C1-C4) alkyl, O—(C1-C4) alkyl, and S(O)2CH3, wherein the alkyl is unsubstituted or mono-, di- or trisubstituted by F,

provided that when A is (C6-C14) aryl and one of R4 and R5 is halogen or (C0-C6) alkylene-O—(C0-C6) alkylene-H, then the other one of R4 and R5 is not halogen or (C0-C6) alkylene-O—(C0-C6) alkylene-H;

R6 is selected from the group consisting of H, (C1-C4) alkyl and (C0-C2) alkylene-(C6-C10) aryl, wherein the alkyl is unsubstituted or mono, di- or trisubstituted by (C0-C4) alkylene-O—(C0-C4)-alkylene-H, and the aryl is unsubstituted or mono, di- or trisubstituted by F; and

R7, R8 and R9 are H;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

4. The compound according to claim 1 , wherein

R1 is selected from the group consisting of (C1-C6) alkyl, phenyl and (C3-C6) cycloalkyl;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

5. The compound according to claim 4 , wherein

R1 is isopropyl;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

6. The compound according to claim 5 , wherein

A is phenyl; and

R4 is CF3 and is in the para- position;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

7. The compound according to claim 1 , wherein

n is 1; and

A is (C6-C14) aryl;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

8. The compound according to claim 1 , wherein

A is phenyl, naphthyl or pyridyl;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

9. The compound according to claim 8 , wherein A is phenyl;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

10. The compound according to claim 1 , wherein

A is phenyl;

R4 is in ortho position; and

R5 is in para position;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

11. The compound according to claim 10 , wherein

R4 is O—(C1-C4) alkyl and in ortho position;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

12. The compound according to claim 11 , wherein

R4 is methoxy or ethoxy;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

13. The compound according to claim 12 , wherein

R4 is ethoxy;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

14. The compound according to claim 13 , wherein

R5 is (C1-C4) alkyl, mono-, di- or trisubstituted by F;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

15. The compound according to claim 14 wherein

R5 is CF3;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

16. The compound according to claim 15 , wherein

R6 is (C1-C6) alkyl;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

17. The compounds according to claim 16 , wherein

R7 is H;

or a stereoisomer, enantiomer, tautomer, or salt thereof.

18. A pharmaceutical comprising at least one compound according to claim 1 , or a stereoisomer, enantiomer, tautomer, or pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable excipient.

19. The pharmaceutical composition according to claim 18 , further comprising at least one additional active compound, wherein the additional active compound is therapeutically effective in the treatment of diabetes mellitus or dyslipidemia.

20. The pharmaceutical composition according to claim 19 wherein the additional active compounds is selected from the group consisting of anti-diabetics.

21. The pharmaceutical composition according to claim 19 wherein the additional active compound is selected from the group consisting of lipid modulators.

22. A method for treating diabetes mellitus, in a patient in thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 , or a stereoisomer, enantiomer, tautomer, or salt thereof.

23. A method for treating dyslipidemia, in a patient in thereof, comprising administering to the patient a pharmaceutically effective amount of the compound according to claim 1 , or a stereoisomer, enantiomer, tautomer, or salt thereof.

24. A process for preparing a pharmaceutical composition comprising at least one compound according to claim 1 , or a stereoisomer, enantiomer, tautomer, or pharmaceutically acceptable salt thereof, in combination with a pharmaceutically acceptable excipient which comprises mixing the compound according to claim 1 , or a stereoisomer, enantiomer, tautomer, or pharmaceutically acceptable salt thereof, with the pharmaceutically acceptable excipient into a form suitable for administration to a patient in need thereof.