3-spirocyclic piperidine derivatives as ghrelin receptor agonists

1. A compound of formula (I)

wherein

is a single bond;

X 1 is (CR x1 H) n and X2 is (CH);

n is 1;

R x1 is selected from hydrogen and C 1-6 alkyl;

m is 1 and p is 1; or

Y is NR 1 ;

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

R 2a is

-A-phenyl;

wherein the phenyl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, hydroxy, C 1-6 alkyl, C 1-6 alkoxy and C 1-6 haloalkyl;

A is selected from a bond, —(CR A1 R A2 )—, —(CR A1 R A2 )(CR A1 R A2 )—, —(CR A1 R A2 )—O—, and —O—(CR A1 R A2 )—;

R A1 and R A2 are independently selected from hydrogen and C 1-6 alkyl;

R 2b is hydrogen or C 1-4 alkyl;

R 3 and R 4 are independently selected from hydrogen and C 1-6 alkyl

R 6 and R 7 are independently selected from hydrogen and C 1-6 alkyl;

R 5 is phenyl, which is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, C 1-6 alkyl, C 1-6 alkoxy and C 1-6 haloalkyl;

or a pharmaceutically acceptable salt thereof.

2. The compound according to claim 1 , wherein R 5 is phenyl and is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen and C 1-6 alkyl.

3. The compound according to claim 1 , wherein R 2a is -A-phenyl, unsubstituted or substituted with 1 to 3 substituents independently selected from C 1-6 alkyl, C 1-6 alkoxy and halogen.

4. The compound of 1, which is selected from the group consisting of:

2-Amino-N-[(R)-1-benzyloxymethyl-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;

2-Amino-N-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro [4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-3-(benzyloxy)-1-oxo-1-(1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)propan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-3-(benzyloxy)-1-(2-isopropyl-1-oxo-4-phenyl-2,7-diaza spiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-3-(benzyloxy)-1-(4-(4-chlorophenyl)-2-methyl-1-oxo-2,7-diaza spiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-2-methyl-N-((2R)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-3-(1-methyl-1H-indol-3-yl)-1-oxopropan-2-yl)propanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-ethyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-1-(4-(4-fluorophenyl)-2-isopropyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-H-indol-3-yl)-1-oxopropan-2-yl)-2-methyl propanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-(2-(dimethylamino)-2-oxoethyl)-1-oxo-4-phenyl-2,7-diaza spiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-isopropyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

N-((2R)-3-(1H-indol-3-yl)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-amino-2-methylpropanamide;

2-amino-2-methyl-N-((2R)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-5-phenylpentan-2-yl)propanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-ethyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-2-methyl-N-((2R)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-4-phenylbutan-2-yl)propanamide;

2-amino-N-((2R)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-3-(4-methylbenzyloxy)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(3-methoxybenzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-5-phenylpentan-2-yl)-2-methylpropanamide;

2-amino-2-methyl-N-((2R)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-5-phenylpentan-2-yl)propanamide;

2-amino-N-((2R)-1-(4-(4-fluorophenyl)-2-isopropyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-3-(1H-indol-3-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-Amino-N-{(R)-1-benzyloxymethyl-2-[2-(2,2-dimethly-propyl)-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl]-2-oxo-ethyl}-2-methyl-propionamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxobutan-2-yl)-2-methylpropanamide;

2-Amino-N-{(R)-1-benzyloxymethyl-2-(2-isobutyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl}-2-methyl-propionamide;

2-Amino-N-{(R)-1-benzyloxymethyl-2-[4-(4-chloro-phenyl)-2-methyl-1-oxo-2,7-diaza-spiro[4.5]dec-7-yl]-2-oxo-ethyl}-2-methyl-propionamide;

2-Amino-N-[(R)-1-benzyloxymethyl-2-(2-isopropyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;

2-Amino-N-[(R)-1-benzyloxymethyl-2-oxo-2-(1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-ethyl]-2-methyl propionamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-o-tolyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-p-tolyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-2-methyl-N-((2R)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-3-(4-methylbenzyloxy)-1-oxopropan-2-yl)propanamide;

2-amino-N-((2R)-3-(4-chlorobenzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-(pyridin-3-yl)-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(cyclohexylmethoxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

N-((2R)-3-(1H-Indol-3-yl)-1-(2-isopropyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-amino-2-methylpropanamide;

2-Amino-N-[(R)-1-benzyloxymethyl-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-3-hydroxy-2-methyl-propionamide;

2-Amino-N-[(R)-1-(4-methoxy-benzyloxymethyl)-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;

2-Amino-N-[(R)-2-[4-(4-fluoro-phenyl)-2-methyl-1-oxo-2,7-diaza-spiro[4.5]dec-7-yl]-1-(4-ethoxy-benzyloxy methyl)-2-oxo-ethyl]-2-methyl-propionamide;

2-Amino-N-[(R)-1-(4-fluoro-benzyloxymethyl)-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;

2-Amino-N-[(R)-1-(3,4-difluoro-benzyloxymethyl)-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;

2-Amino-N-[(R)-1-(2,4-difluoro-benzyloxymethyl)-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;

2-amino-N-((2R)-3-(3-methoxybenzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(2,4-difluorobenzyloxy)-1-(4-(3,4-difluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(4-fluorobenzyloxy)-1-(2-methyl-1-oxo-4-p-tolyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(4-(3,5-difluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(3,4-difluorobenzyloxy)-1-(4-(3,4-difluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(4-(3,4-difluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-1-(4-(3,4-difluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-3-(4-fluorobenzyloxy)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-3-(2-methylbenzyloxy)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(4-fluorobenzyloxy)-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-1-(4-(4-fluorophenyl)-2-methyl-l-oxo-2,7-diazaspiro[4.5]decan-7-yl)-3-(3-methylbenzyloxy)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((R)-3-(2,3-dihydro-1H-inden-2-yl)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)-1-(4-(4-fluorophenyl)-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-5-phenylpentan-2-yl)-2-methylpropanamide;

2-amino-2-methyl-N-((2R)-1-(2-methyl-1-oxo-4-p-tolyl-2,7-diazaspiro [4.5] decan-7-yl)-3-(2-methylbenzyloxy)-1-oxopropan-2-yl)propanamide;

2-amino-2-methyl-N-((R)-1-(2-methyl-I -oxo-4-phenyl-2,7-diazaspiro [4.5]decan-7-yl)-1-oxo-5-phenylpent-4-en-2-yl)propanamide;

2-amino-N-((S)-3-(benzylthio)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro [4.5] decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;

2-amino-N-((2R)3-(benzyloxy)-1-(2-methyl-1-oxo-4-p-tolyl-2,7-diazaspiro [4.5]decan-7-yl)-1-oxobutan-2-yl)-2-methylpropanamide;

2-amino-2-methyl-N-((R)-1-(2-methyl-I -oxo-4-phenyl-2,7-diazaspiro [4.5] de can-7-yl)-1-oxo-3-(pyridin-2-ylmethoxy)propan-2-yl)propanamide;

2-amino-N-((R)-3-(benzyloxy)-1-oxo-1-(1-oxo-4-phenyl-2-(2,2,2-trifluoroethyl)-2,7-diazaspiro[4.5]decan-7-yl)propan-2-yl)-2-methylpropanamide;

2-amino-N-((R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro [4.5] decan-7-yl)-1-oxopropan-2-yl)-2-methylbutanamide;

2-Amino-2-methyl-N-((R)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro [4.5] decan-7-yl)-1-oxo-4-phenoxybutan-2-yl)propanamide;

or a pharmaceutically acceptable salt thereof.

5. A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt according to claim 1 and one or more pharmaceutically acceptable carriers.

6. The compound of claim 1 , which is 2-Amino-N-[(R)-1-benzyloxymethyl-2-(2-methyl-1-oxo-4-phenyl-2,7-diaza-spiro[4.5]dec-7-yl)-2-oxo-ethyl]-2-methyl-propionamide or a pharmaceutically acceptable salt thereof.

7. The compound of claim 1 , which is 2-amino-N-((2R)-3-(benzyloxy)-1-((4S,5R)-4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro [4.5] decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide or a pharmaceutically acceptable salt thereof.

8. The compound of claim 1 , which is 2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-4-p-tolyl-2,7-diazaspiro [4.5] decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide or a pharmaceutically acceptable salt thereof.

9. The compound of claim 6 , which is an L-malate salt.

10. The compound of claim 7 , which is an L-malate salt.

11. The compound of claim 8 , which is an L-malate salt.