Compounds, methods and formulations for the oral delivery of a glucagon-like peptide (GLP)-1 compound or a melanocortin-4 receptor (MC4) agonist peptide

1. A compound of formula I:

wherein:

R 1 and R 2 are each independently H, OH, cyano, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF 3 , halo or NR 4 R 4′ ;

R 3 is H or C 1 -C 6 alkyl;

X is

optionally substituted with C 1 -C 4 alkyl;

wherein the Y containing cyclic group is attached at position number 4 of the oxazole ring X, and the (CH 2 ) n —CO 2 R 3 moiety is attached at position number 2 of the oxazole ring X;

Y is S, CR 5 ═N or N═CR 5 ;

n is 2, 3, 4, 5, 6 or 7;

R 4 is H, COR 6 , SO 2 R 7 , or C 1 -C 6 alkyl;

R 4′ is H or C 1 -C 6 alkyl;

R 5 is H or forms a bond with X;

R 6 is H or C 1 -C 6 alkyl; and

R 7 is H or C 1 -C 6 alkyl;

or a pharmaceutical salt thereof.

2. The compound of claim 1 wherein R 1 and R 2 are each independently H, OH, C 1 -C 6 alkyl, C 1 -C 6 alkoxy, CF 3 , halo or NR 4 R 4′ and wherein X is not substituted with C 1 -C 4 alkyl.

3. The compound of claim 1 wherein R 3 is H.

4. The compound of claim 1 wherein X is

5. A compound which is

or a pharmaceutical salt thereof.

6. A compound which is

or a pharmaceutical salt thereof.

7. A compound which is

or a pharmaceutical salt thereof.

8. A compound which is

or a pharmaceutical salt thereof.

9. A compound which is

or a pharmaceutical salt thereof.

10. A pharmaceutical composition comprising:

a) a compound of any one of claims 5 - 9 or a pharmaceutical salt thereof; and

b) a GLP-1 compound.

11. The composition of claim 10 wherein the GLP-1 compound is Val 8 -Glu 22 -GLP-1(7-37)OH.

12. A pharmaceutical composition comprising:

a) a compound of any one of claims 5 - 9 or a pharmaceutical salt thereof; and

b) an MC4 agonist peptide.

13. The composition of claim 12 wherein the MC4 agonist peptide is selected from the group consisting of:

Ac-Arg-cyclo[Cys-Glu-His-D-Phe-Arg-Trp-Cys]-NH 2 ;

Ac-cyclo[hCys-His-D-Phe-Arg-Trp-Cys]-NH 2 ;

Ac-cyclo[hCys-His-D-Phe-Arg-Trp-penicillamine]-NH 2 ; and

N-cyclohexanecarbonyl-cyclo [hCys-His-D-Phe-Arg-Trp-penicillamine]-NH 2 .

14. A pharmaceutical composition comprising:

a) a compound of claim 1 ; and

b) a GLP-1 compound.

15. A pharmaceutical composition comprising:

a) a compound of claim 1 ; and

b) an MC4 agonist peptide.