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:

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;

R 4 is H, COR 5 , SO 2 R 6 or C 1 -C 6 alkyl;

R 4′ is H or C 1 -C 6 alkyl;

R 5 is H or C 1 -C 6 alkyl;

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

n is 4, 5, 6 or 7;

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′ .

3. The compound of claim 1 wherein R 1 and R 2 are each independently H, O(C 1 -C 4 alkyl) or OH.

4. A pharmaceutical composition comprising:

a) a compound of claim 1 or a pharmaceutical salt thereof; and

b) a GLP-1 compound.

5. The composition of claim 4 wherein the GLP-1 compound is Val 8 -Glu 22 -GLP-1 (7-37)OH.

6. A pharmaceutical composition comprising:

a) a compound of claim 1 or a pharmaceutical salt thereof; and

b) an MC4 agonist peptide.

7. The composition of claim 6 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]-NH2

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

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

8. The compound of claim 1 which is

or a pharmaceutical salt thereof.

9. A compound selected from

and pharmaceutically acceptable salts thereof.

10. A compound which is

or a pharmaceutically acceptable salt thereof.

11. The pharmaceutical composition of claim 4 , wherein the GLP-1 compound is a GLP-1 derivative.

12. The pharmaceutical composition of claim 4 , wherein the GLP-1 compound is a GLP-1 analog.

13. A compound of formula I:

wherein

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

R 3 is H;

R 4 is H, COR 5 , SO 2 R 6 or C 1 -C 6 alkyl;

R 4′ is H or C 1 -C 6 alkyl;

R 5 is H or C 1 -C 6 alkyl;

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

X is a 5 membered aromatic heterocycle that is optionally substituted with C 1 -C 4 alkyl; wherein said heterocycle contains two or three heteroatoms selected from N, S, and O wherein at least one heteroatom must be N and wherein said heterocycle may not be 1,3,4,-oxadizole or 1,3-oxazole;

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

or a pharmaceutical salt thereof.

14. 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;

R 4 is H, COR 5 , SO 2 R 6 or C 1 -C 6 alkyl;

R 4′ is H or C 1 -C 6 alkyl;

R 5 is H or C 1 -C 6 alkyl;

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

X is a 5 membered aromatic heterocycle that is optionally substituted with C 1 -C 4 alkyl; wherein said heterocycle contains two or three heteroatoms selected from N, S, and O wherein at least one heteroatom must be N and wherein said heterocycle may not be 1,3,4,-oxadizole or 1,3-thiazole;

n is 2, 3, 4, or 5;

or a pharmaceutical salt thereof.