1,2,4-oxadiazole derivatives as drugs modulating the GLP-1 peptide receptor

1. A method for the treatment, in a mammal suffering or being susceptible to suffer from a disease in which the GLP-1 receptor participates or mediates for a) reducing body fat inducing satiety and controlling intake or for b) the treatment of a disease selected from an eating disorder and a disease selected from the list comprising obesity, anorexia, lipid dysfunction, diabetes, hyperinsulism, metabolic syndrome and cardiovascular diseases, the method comprising administering to said mammal an effective amount of a compound of formula (I):

together with a pharmaceutically acceptable vehicle,

wherein

R 1 is selected from C 6 -C 15 aryl, C 3 -C 15 heteroaryl, C 7 -C 15 arylalkyl and C 3 -C 15 heteroarylalkyl;

R 2 is selected from hydrogen, C 1 -C 6 alkyl and C 2 -C 6 alkenyl;

wherein each R 3 is independently selected from the group consisting of:

C 2 -C 15 heterocyclyl,

C 3 -C 15 heteroaryl,

C 3 -C 15 heterocyclylalkyl,

C 1 -C 6 alkyl, optionally substituted with —N(R 7 )(R 8 ), —C(O)R 7 , a 5 or 6-membered heterocycle, 5 or 6-membered heteroaryl, —OR 7 ;

—OR 5

—C(O)R 5 ,

—C(O)N(R 5 )(R 6 ), and

—N(R 5 )(R 6 ),

R 5 and R 6 are independently selected from the group consisting of hydrogen, C 1 -C 6 alkyl, C 3 -C 7 cycloalkyl, C 6 -C 15 aryl, C 3 -C 15 heteroaryl, C 2 -C 15 heterocyclyl, C 7 -C 15 arylalkyl, C 3 -C 15 heteroarylalkyl, —S(O) 2 R 9 , —N(H)(R 9 );

R 9 is independently selected from the group consisting of C 1 -C 3 alkyl, C 6 -C 10 aryl, C 7 -C 11 arylalkyl and an amino acid;

each of these groups being able to be optionally substituted with a group which is selected from C 1 -C 6 alkyl, C 1 -C 6 haloalkyl, C 2 -C 6 alkenyl, C 2 -C 6 alkynyl, —OR 7 , —SR 7 , —S(O)R 7 , —S(O) 2 R 7 , —OS(O) 2 R 7 , —N(R 7 )(R 8 ), —C(O)R 7 , —C(O)OR 8 , —C(O)N(R 7 )(R 8 ), —OC(O)R 7 and —N(R 7 )C(O)R 8 ; R 7 and R 8 being independently selected from the group consisting of C 1 -C 3 alkyl, C 6 -C 15 aryl, C 3 -C 15 heteroaryl, C 2 -C 15 heterocyclyl, C 7 -C 15 arylalkyl, C 3 -C 15 heteroarylalkyl, C 3 -C 15 heterocyclylalkyl; optionally substituted with C 1 -C 3 alkyl, C 1 -C 3 haloalkyl or —O—(C 1 -C 3 )alkyl;

y is 1, 2, 3, 4 or 5; and

or a pharmaceutically acceptable solvate or salt thereof.

2. The method according to claim 1 , wherein R 1 is selected from C 6 -C 15 aryl, C 3 -C 15 heteroaryl, C 7 -C 15 arylalkyl and C 3 -C 15 heteroarylalkyl; optionally substituted with C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OR 7 or —SR 7 , wherein R 7 is as defined in claim 1 .

3. The method according to claim 2 , wherein R 1 is a radical of general formula (II):

wherein

n is 0, 1, 2, 3 or 4,

m is 0, 1, 2, 3, 4 or 5, and

R 4 is selected from the group consisting of C 1 -C 3 alkyl, C 1 -C 3 haloalkyl, —OR 7 , —SR 7 ; R 7 being selected from the group consisting of C 1 -C 3 alkyl, C 6 -C 15 aryl, C 3 -C 15 heteroaryl, C 2 -C 15 heterocyclyl, C 7 -C 15 arylalkyl, C 3 -C 15 heteroarylalkyl, C 3 -C 15 heterocyclylalkyl.

4. The method according to claim 3 , wherein R 1 is selected from

5. The method according to claim 1 , wherein each R 3 is independently selected from:

6. The method according to claim 1 , wherein R 2 is hydrogen.

7. The method according to claim 1 , wherein y is 1 or 2.

8. The method according to claim 1 , wherein the compound of formula (I) is selected from:

the stereoisomers thereof, or a pharmaceutically acceptable solvate or salt thereof.

9. The method according to claim 1 , wherein the compound of formula (I) is selected from:

-3-phenyl-1-[(3R)-1-[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-3-yl]propan-1-one,

1[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-4-carboxamide,

5-[[(2S)-2-(2-pyridin-2-ylethyl)piperidin-1-yl]methyl]-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole,

4-[[1-[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-3-yl]methyl]morpholine,

5-[[(3S)-3-[(4-methoxyphenoxy)methyl]piperidin-1-yl]methyl]-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole,

5-[(4-thiomorpholin-4-ylpiperidin-1-yl)methyl]-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole,

phenyl-[(3R)-1-[[3-[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-3-yl]methanone,

5-[[4-(pyridin-2-ylmethoxy)piperidin-1-yl]methyl]-3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazole,

3-benzyl-5-[[4-(3,4-dihydro-1H-isoquinolin-2-yl)piperidin-1-yl]methyl]-1,2,4-oxadiazole, and

(3R)-1-[[[[3-[4-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-5-yl]methyl]piperidin-3-carboxamide,

or a pharmaceutically acceptable solvate or salt thereof.

10. A cosmetic method for the treatment of a condition in which the GLP-1 receptor participates or mediates, wherein said condition is obesity, the method comprising administering to said mammal an effective amount of a compound of formula (I) as defined in claim 1 together with a pharmaceutically acceptable vehicle.

11. A cosmetic composition comprising a compound of formula (I) as defined in claim 1 and a cosmetically acceptable vehicle.