3-Spirocyclic Piperidine Derivatives as Ghrelin Receptor Agonists

Abstract

The invention relates to derivatives of formula (I), wherein the substituents are as defined in the specification; to processes for the preparation of such derivatives; pharmaceutical compositions comprising such derivatives; such derivatives as a medicament; such derivatives for the treatment of a disorder or a disease mediated by the ghrelin receptor.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
            is a single bond or a double bond; 
         X 1  is (CR x1 H) n  and X 2  is (CH); or 
         X 1  is (CR x1 H) n  and X 2  is N; or 
         X 1  is NR x1  and X 2  is (CH); or 
         X 1  is NR x1  and X 2  is N; or 
         X 1  is N and X 2  is C; wherein the bond between X 1  and X 2  is a double bond if X 1  is N and X 2  is C; 
         n is 0 or 1; 
         R x1  is selected from hydrogen and C 1-6 alkyl; 
         m is 1 and p is 0; or 
         m is 1 and p is 1; or 
         m is 2 and p is 1; 
         Y is NR 1  or O; 
         R 1  is selected from hydrogen, C 1-6 alkyl, —C 1-4 alkylC(O)NR 1a R 1b , —C 1-4 alkylC(O)OC 1-4 alkyl, —C 1-4 alkylC(O)OC 1-4  haloalkyl, C 1-6 haloalkyl, C 3-6 cycloalkyl, —C 1-4 alkyl-5-6 membered heteroaryl, hydroxyC 1-6 alkyl, C 1-6 alkoxy and C 1-4 alkoxyC 1-4 alkyl; 
         wherein the 5-6 membered heteroaryl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen and C 1-6 alkyl; 
         R 1a  and R 1b  are independently selected from hydrogen, C 1-6 alkyl and C 1-6 haloalkyl; or 
         R 1a  and R 1b  together with the nitrogen to which they are attached form a 4-6 membered heterocyclic ring containing 0, 1 or 2 additional heteroatoms selected from oxygen, nitrogen and sulphur; 
         R 2a  is selected from 
         (i) -A-phenyl; 
         (ii) -A-5-6 membered heteroaryl; 
         (iii) -A-4-6 membered heterocyclyl; 
         (iv) -A-C 6-6 cycloalkyl; 
         (v) -D-8-10 membered fused bicyclic ring system; 
         wherein the phenyl, 5-6 membered heteroaryl, 4-6 membered heterocyclyl, C 5-6 cycloalkyl and 8-10 membered fused bicyclic ring system are 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—, —O—(CR A1 R A2 )—, —(CR A1 R A2 )—S—, —(CR A1 R A2 )—S(O)—, —(CR A1 R A2 )—S(O) 2 —, —S—(CR A1 R A2 )—, —S(O)—(CR A1 R A2 )—, —S(O) 2 —(CR A1 R A2 )—, —NR A3 —(CR A1 R A2 )—, —(CR A1 R A2 )—NR A3 — and —(CR A1 )═(CR A1 )—; 
         D is a bond, —O— or —(CR D1 R D2 )—; 
         R A1 , R A2  and R A3  are independently selected from hydrogen, C 1-6 alkyl and halogen; 
         R D1  and R D2  are independently selected from hydrogen, C 1-6 alkyl and halogen; 
         R 2b  is hydrogen or C 1-4 alkyl; 
         R 3  and R 4  are independently selected from hydrogen, C 1-6 alkyl and C 3-6 cycloalkyl; or R 3  and R 4  together with the nitrogen to which they are attached form a 4-6 membered heterocyclic ring containing 0, 1 or 2 additional heteroatoms selected from oxygen, nitrogen and sulphur; which 4-6 membered heterocyclic ring is unsubstituted or substituted with 1 or 2 halogen substituents; 
         R 6  and R 7  are independently selected from hydrogen, C 1-6 alkyl, C 1-6 hydroxyalkyl and C 1-6 haloalkyl; 
         R 5  is selected from phenyl, a 5-6 membered heteroaryl, C 3-6 cycloalkyl and 4-6 membered heterocyclyl; which phenyl, 5-6 membered heteroaryl, C 3-6 cycloalkyl and 4-6 membered heterocyclyl 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 the compound is of formula (Ia) 
       
         
           
           
               
               
           
         
         wherein X 1  is (CR x1 H) n  and X 2  is (CH) or X 1  is NR x1  and X 2  is (CH). 
       
     
     
         3 . The compound according to  claim 1 , wherein the compound is of formula (Ib) 
       
         
           
           
               
               
           
         
         wherein X 1  is (CR x1 H) n  and X 2  is (CH) or X 1  is NR x1  and X 2  is (CH). 
       
     
     
         4 . The compound according to  claim 1 , wherein the compound is of formula (Ic) 
       
         
           
           
               
               
           
         
       
     
     
         5 . The compound according to  claim 1 , wherein the compound is of formula (Id) 
       
         
           
           
               
               
           
         
       
     
     
         6 . The compound according to  claim 1 , wherein the compound is of formula (Ie) 
       
         
           
           
               
               
           
         
         wherein X 1  is (CR x1 H) n  and X 2  is (CH) or X 1  is NR x1  and X 2  is (CH). 
       
     
     
         7 . The compound according to  claim 1 , wherein the compound is of formula (If) 
       
         
           
           
               
               
           
         
         wherein X 1  is (CR x1 H) n  and X 2  is (CH) or X 1  is NR x1  and X 2  is (CH). 
       
     
     
         8 . The compound according to  claim 1 , wherein the compound is of formula (Ig) 
       
         
           
           
               
               
           
         
         wherein X 1  is (CR x1 H) n  and X 2  is (CH) or X 1  is NR x1  and X 2  is (CH). 
       
     
     
         9 . The compound according to  claim 1 , wherein the compound is of formula (Ih) 
       
         
           
           
               
               
           
         
         wherein X 1  is (CR x1 H) n  and X 2  is (CH) or X 1  is NR x1  and X 2  is (CH). 
       
     
     
         10 . The compound according to  claim 1 , wherein Y is NR 1 . 
     
     
         11 . The compound according to  claim 10 , wherein Y is NR 1  and R 1  is selected from hydrogen, C 1-6 alkyl, C 1-6  haloalkyl, —C 1-4 alkylC(O)NR 1a R 1b , —C 1-4  alkylC(O)OC 1-4 alkyl, and —C 1-4 alkyl-5-6 membered heteroaryl, wherein the 5-6 membered heteroaryl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen and C 1-6 alkyl. 
     
     
         12 . The compound according to  claim 1 , wherein X 1  is (CR x1 H) n . 
     
     
         13 . The compound according to  claim 1 , wherein X 1  is (CR x1 H) n  and n is 1. 
     
     
         14 . The compound according to  claim 1 , wherein R 5  is selected from phenyl and a 5-6 membered heteroaryl, which phenyl or 5-6 membered heteroaryl is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen and C 1-6 alkyl. 
     
     
         15 . The compound according to  claim 1 , wherein R 2a  is selected from -A-phenyl, -A-5-6 membered heteroaryl, -A-4-6 membered heterocyclyl, -A-C 5-6 cycloalkyl and a -D-8-10 membered fused bicyclic ring system, which phenyl, 5-6 membered heteroaryl, 4-6 membered heterocyclyl, -A-C 5-6 cycloalkyl and 8-10 membered fused bicyclic ring system are unsubstituted or substituted with 1 to 3 substituents independently selected from C 1-6 alkyl, C 1-6 alkoxy and halogen. 
     
     
         16 . The compound according to  claim 1 , wherein R 3  and R 4  are both hydrogen. 
     
     
         17 . The compound according to  claim 1 , wherein R 6  and R 7  are independently selected from hydrogen, C 1-6 alkyl and C 1-6 hydroxyalkyl. 
     
     
         18 . 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;   N-((2R)-3-(Benzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methyl-2-(methylamino) propanamide;   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-2-methyl-N-((2R)-1-(2-methyl-1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonan-6-yl)-3-(1-methyl-1H-indol-3-yl)-1-oxopropan-2-yl)propanamide;   2-Amino-N-{(R)-1-benzyloxymethyl-2-[2-(2,2-dimethyl-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-((2R)-3-(benzyloxy)-1-(1-(4-fluorophenyl)-2-methyl-3-oxo-2,6-diazaspiro[3.5]nonan-6-yl)-1-oxopropan-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-(3-methyl-4-oxo-1-phenyl-2,3,7-triaza-spiro[4.5]dec-1-en-7-yl)-2-oxo-ethyl]-2-methyl-propionamide;   2-Amino-N—[(R)-1-benzyloxymethyl-2-(3-methyl-4-oxo-1-phenyl-1,3,7-triaza-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;   2-amino-N-((2R)-3-(benzyloxy)-1-(3-methyl-4-oxo-1-phenyl-1,3,7-triazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methylpropanamide;   2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonan-6-yl)-1-oxopropan-2-yl)-2-methylpropanamide;   2-amino-N-((2R)-3-(benzyloxy)-1-(2-methyl-1-oxo-3-phenyl-2,6-diazaspiro[3.5]nonan-6-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-(1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxo-4-(tetrahydro-2H-pyran-4-yl)butan-2-yl)-2-methylpropanamide;   2-amino-N-((2R)-3-(benzyloxy)-1-(4-(4-fluorophenyl)-2-((5-methylisoxazol-3-yl)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)-2-(oxazol-2-ylmethyl)-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-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;   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-methyl-2-(methylamino)propanamide;   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-methyl-2-(methylamino)propanamide;   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-1-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-N-((2R)-4-cyclohexyl-1-(4-(4-fluorophenyl)-2-methyl-1-oxo-2,7-diazaspiro[4.5]decan-7-yl)-1-oxobutan-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-1-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;   N-((2R)-3-(4-fluorobenzyloxy)-1-(2-methyl-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-7-yl)-1-oxopropan-2-yl)-2-methyl-2-(methylamino)propanamide;   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-1-oxo-4-phenyl-2,7-diazaspiro[4.5]decan-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;   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-methyl-2-(methylamino)propanamide; and   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.   
     
     
         19 . A pharmaceutical composition comprising a therapeutically effective amount of a compound or salt according to  claim 1  and one or more pharmaceutically acceptable carriers. 
     
     
         20 . A combination comprising a therapeutically effective amount of the compound or salt according to  claim 1  and one or more therapeutically active co-agents. 
     
     
         21 . A method of treating a disorder or a disease in a subject mediated by the ghrelin receptor, wherein the method comprises administering to the subject a therapeutically effective amount of a compound or salt according to  claim 1 .