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

wherein the Y containing cyclic group is attached at position number 3 of the oxadiazole ring X, and the (CH 2 ) n —CO 2 R 3 moiety is attached at position number 5 of the oxadiazole ring X;

Y is S, CR 5 ═N or N═CR 5 ;

n is 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 pharmaceutically acceptable salt thereof

wherein said compound of formula I is not:

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. A compound which is

or a pharmaceutical salt thereof.

5. A pharmaceutical composition comprising:

a) a compound of claim 1 ; and

b) a GLP-1 compound.

6. The composition of claim 5 , wherein the GLP-1 compound is Val 8 -Glu 22 -GLP-1(7-37)OH.

7. A pharmaceutical composition comprising:

a) a compound of claim 1 ; and

b) an MC4 agonist peptide.

8. The composition of claim 7 , 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 .

9. A pharmaceutical composition comprising:

a) 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

wherein the Y containing cyclic group is attached at position number 3 of the oxadiazole ring X, and the (CH 2 ) n —CO 2 R 3 moiety is attached at position number 5 of the oxadiazole 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 pharmaceutically acceptable salt thereof, wherein said compound of formula I is not:

 and

b) a pharmaceutically acceptable carrier.

10. The composition of claim 9 , further comprising a GLP-1 compound.

11. The composition of claim 9 , further comprising an MC4 agonist peptide.

12. The composition of claim 5 , wherein the GLP-1 compound is a GLP-1 fragment, GLP-1 analog or GLP-1 derivative.

13. The composition of claim 10 , wherein the GLP-1 compound is a GLP-1 fragment, GLP-1 analog or GLP-1 derivative.