Melanocortin receptor agonists

1. A compound of the following formula 1,

wherein

R 1 represents hydrogen, or represents C 1 -C 10 -alkyl, C 3 -C 7 -cycloalkyl, C 6 -C 10 -aryl, heterocycle or heteroaryl, each of which is unsubstituted or substituted with at least one substituent selected from the group consisting of halogen, amino, C 1 -C 4 -alkyl, trifluoromethyl, hydroxy, C 1 -C 4 -alkoxy, cyano and oxo;

R 2 represents phenyl or six-membered heteroaryl, each of which is unsubstituted or mono- or di-substituted with substituent(s) selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, cyano and amino;

R 3 represents hydrogen, or represents C 1 -C 6 -alkyl or C 3 -C 7 -cycloalkyl, each of which is unsubstituted or substituted with substituent(s) selected from the group consisting of halogen, methyl, trifluoromethyl, hydroxy and amino;

R 4 represents C 4 -C 7 -cycloalkyl or monocyclic heterocycle, each of which is unsubstituted or mono- or poly-substituted with substituent(s) selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, trifluoromethyl, C 1 -C 4 -alkoxy and oxo; or represents phenyl or six-membered heteroaryl, each of which is unsubstituted or mono- or di-substituted with substituent(s) selected from the group consisting of halogen, hydroxy, C 1 -C 4 -alkyl, trifluoromethyl, C 1 -C 4 -alkoxy and amino; and

R 5 represents C 1 -C 6 -alkyl, difluoromethyl, trifluoromethyl, C 3 -C 8 -cycloalkyl, amino, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, phenyl, monocyclic heteroaryl or monocyclic heterocycle where alkyl is unsubstituted or substituted with at least one substituent selected from the group consisting of fluoro, hydroxy, mercapto, C 1 -C 4 alkoxy, acetoxy, amino, acetylamino, cyano, carbamoyl, dimethyl carbamoyl and oxo and phenyl or heteroaryl is unsubstituted or mono- or di-substituted with substituent(s) selected from the group consisting of halogen, hydroxy, methyl, trifluoromethyl, methoxy and amino, in which, heteroaryl represents imidazole, oxazole, thiazole, pyrazole, triazole, pyridine, pyrimidine, pyridazine or furan, and heterocycle represents oxazoline, imidazoline, thiazoline, tetrahydropyran, tetrahydrothiopyran, piperidine, tetrahydrofuran or dihydrofuran,

or pharmaceutically acceptable salt or stereoisomer thereof.

2. The compound of formula 1 according to claim 1 , wherein R 1 represents hydrogen, methyl, ethyl, trifluoroethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; or represents phenyl, oxazolinyl, imidazolinyl, thiazolinyl, tetrahydropyranyl, tetrahydrothiopyranyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, pyridinyl, pyrimidinyl, piperidinyl or pyridazinyl, each of which is unsubstituted or substituted with substituent(s) selected from the group consisting of halogen, methyl, cyano, oxo and hydroxy,

or pharmaceutically acceptable salt or stereoisomer thereof.

3. The compound of formula 1 according to claim 2 , wherein R 1 represents isopropyl, tert-butyl or cyclopropyl; or represents phenyl, tetrahydropyranyl, thiazolyl, pyridinyl, pyrimidinyl or pyridazinyl, each of which is unsubstituted or substituted with substituent(s) selected from the group consisting of halogen, methyl, cyano and hydroxy,

or pharmaceutically acceptable salt or stereoisomer thereof.

4. The compound of formula 1 according to claim 1 , wherein R 2 represents phenyl which is unsubstituted or mono- or di-substituted with substituent(s) selected from the group consisting of fluorine, chlorine, bromine, methoxy and methyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

5. The compound of formula 1 according to claim 4 , wherein R 2 represents 4-chlorophenyl or 2,4-difluorophenyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

6. The compound of formula 1 according to claim 1 ,

wherein R 3 represents hydrogen, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, cyclopropyl, cyclobutyl or cyclopentyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

7. The compound of formula 1 according to claim 6 ,

wherein R 3 represents hydrogen, methyl, ethyl or isopropyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

8. The compound of formula 1 according to claim 1 , wherein R 4 represents cyclopentyl, cyclohexyl, cycloheptyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 4-fluorocyclohexyl, 4,4-difluorocyclohexyl or 4-trifluoromethyl-cyclohexyl; or represents phenyl which is unsubstituted or mono- or di-substituted with substituent(s) selected from the group consisting of fluorine, chlorine, methyl and methoxy,

or pharmaceutically acceptable salt or stereoisomer thereof.

9. The compound of formula 1 according to claim 8 , wherein R 4 represents cyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 4,4-difluorocyclohexyl or 2,4-difluorophenyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

10. The compound of formula 1 according to claim 1 , wherein R 5 represents methyl, trifluoromethyl, hydroxymethyl, methoxymethyl, ethoxymethyl, propyl, isopropyl, isobutyl, tert-butyl, —CH 2 CH 2 OH, —CH(CH 3 )CH 2 OH, —C(CH 3 ) 2 CH 2 OH, —C(CH 3 )(CH 2 OH) 2 , —C(CH 3 ) 2 CH 2 OMe, —C(CH 3 ) 2 CH 2 OEt, phenyl, oxazolinyl, imidazolinyl, thiazolinyl, tetrahydropyranyl, imidazolyl, oxazolyl, thiazolyl, pyrazolyl, triazolyl, furanyl, tetrahydrofuranyl, dihydrofuranyl, tetrahydropyranyl, pyridinyl or piperidinyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

11. The compound of formula 1 according to claim 10 , wherein R 5 represents isopropyl, tert-butyl, —C(CH 3 ) 2 CH 2 OH, furanyl or tetrahydrofuranyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

12. The compound of formula 1 according to claim 1 , wherein

R 1 represents isopropyl, tert-butyl or cyclopropyl; or represents phenyl, tetrahydropyranyl, thiazolyl, pyridinyl, pyrimidinyl or pyridazinyl, each of which is unsubstituted or substituted with substituent(s) selected from the group consisting of halogen, methyl, cyano and hydroxy;

R 2 represents 4-chlorophenyl or 2,4-difluorophenyl;

R 3 represents hydrogen, methyl, ethyl or isopropyl;

R 4 represents cyclohexyl, 4-methylcyclohexyl, 4,4-dimethylcyclohexyl, 4,4-difluorocyclohexyl or 2,4-difluorophenyl; and

R 5 represents isopropyl, tert-butyl, —C(CH 3 ) 2 CH 2 OH, furanyl or tetrahydrofuranyl,

or pharmaceutically acceptable salt or stereoisomer thereof.

13. The compound of formula 1 according to claim 12 which is selected from the group consisting of the following:

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)acetamide;

N-[(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-(piperazin-1-ylcarbonyl)pyrrolidin-3-yl]-N-(4,4-dimethylcyclohexyl)acetamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-ethylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-ethylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-ethylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

N-{(3S,5S)-1-[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

N-{(3S,5S)-1-[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-3-hydroxy-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-3-hydroxy-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-ethylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)-3-furamide;

(2R)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-ethylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)acetamide;

N-{(3S,5S)-1-[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)acetamide;

N-{(3S,5S)-1-[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

(2S)—N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5R)-1-[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-3-hydroxy-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)acetamide;

N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)acetamide;

N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)acetamide;

(2R)—N-{(3S,5R)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(6-methylpyridazine-3-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1-(6-chloropyridazine-3-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1,6-dihydropyridazine-3-ylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-phenylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1-(tetrahydro-2H-thiopyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5R)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-isopropylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-2,2-dimethyl-N-(cis-4-methylcyclohexyl)propanamide;

N-{(3S,5R)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(tetrahydro-2H-pyran-4-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4-methylcyclohexyl)acetamide;

(2S)—N-{(3S,5R)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5R)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-cyclopropyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-cyclopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-difluorocyclohexyl)-3-hydroxy-2,2-dimethylpropanamide;

N-{(3S,5R)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-isopropylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)acetamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(6-methylpyridazine-3-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-pyridine-2-ylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-pyridine-2-ylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1,6-dihydropyridazine-3-ylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-pyrimidine-2-ylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(2,4-difluorophenyl)-1-pyridine-2-ylpyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(5-cyanopyridine-2-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(1,3-thiazole-2-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(4,4-dimethylcyclohexyl)-2,2-dimethylpropanamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(2-methylphenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(1-methyl-6-oxo-1,6-dihydropyridazine-3-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-4-(4-chlorophenyl)-1-(6-oxo-1,6-dihydropyridazine-3-yl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3R,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4S)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3R,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(cis-4-methylcyclohexyl)tetrahydrofuran-2-carboxamide;

(2S)—N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(2,4-difluorophenyl)tetrahydrofuran-2-carboxamide;

N-[(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-(piperazin-1-yl carbonyl)pyrrolidin-3-yl]-N-(2,4-difluorophenyl)-2-methylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(2,4-difluorophenyl)-2-methylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(2,4-difluorophenyl)-2,2-dimethylpropanamide;

N-[(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-(piperazin-1-ylcarbonyl)pyrrolidin-3-yl]-N-(2,4-difluorophenyl)-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(2,4-difluorophenyl)-2,2-dimethylpropanamide;

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(4-chlorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(2,4-difluorophenyl)-2-furamide; and

N-{(3S,5S)-1-{[(3S,4R)-1-tert-butyl-4-(2,4-difluorophenyl)pyrrolidin-3-yl]carbonyl}-5-[(4-methylpiperazin-1-yl)carbonyl]pyrrolidin-3-yl}-N-(2,4-difluorophenyl)-2-furamide,

or pharmaceutically acceptable salt or stereoisomer.

14. An agonistic composition to melanocortin receptor comprising the compound of formula 1 as defined in claim 1 , or pharmaceutically acceptable salt or stereoisomer thereof as an active ingredient, together with pharmaceutically acceptable carrier.

15. A method for treatment of obesity comprising

administering the composition according to claim 14 to a subject in need thereof.