2,3-dihydro-1h-inden-1-yl-2,7-diazaspiro[3.5]nonane derivatives

Abstract

The present invention provides a compound of Formula (I) a pharmaceutically salt thereof wherein R 1 , R 2 , Ra, L, Z, Z 1 and Z 2 are as defined herein, that act as Ghrelin antagonists or inverse agonists; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by the antagonism of the Ghrelin receptor.

We claim: 
     
         1 . A compound of Formula (I) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is -L 1 -R 1′ , phenyl or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, where said phenyl or said 5- to 6-membered heteroaryl is optionally fused to a (C 4 -C 7 )cycloalkyl, (C 5 -C 6 )cycloalkenyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, wherein said optionally fused phenyl and said optionally fused 5- to 6-membered heteroaryl is optionally substituted with 1 to 3 substituents selected from halo, hydroxy, oxo, cyano, (C 1 -C 3 )alkyl, halo-substituted (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo-substituted (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkyl-S(O) n —, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkoxy, —(C 0 -C 3 )alkyl NR x R y , —(C 0 -C 3 )alkylNR x C(O)R y , and —(C 0 -C 3 )alkylC(O)NR x R y ; 
 R 1′  is phenyl or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, where said phenyl or said 5- to 6-membered heteroaryl is optionally fused to a (C 4 -C 7 )cycloalkyl, (C 5 -C 6 )cycloalkenyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, wherein said optionally fused phenyl and said optionally fused 5- to 6-membered heteroaryl is optionally substituted with 1 to 3 substituents selected from halo, hydroxy, oxo, cyano, (C 1 -C 3 )alkyl, halo-substituted (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo-substituted (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkyl-S(O) n —, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkoxy, —(C 0 -C 3 )alkylNR x R y , —(C 0 -C 3 )alkylNR x C(O)R y , and —(C 0 -C 3 )alkylC(O)NR x R y ; 
 L 1  is O, S, NH, N(C 1 -C 3 )alkyl or (C 1 -C 3 )alkylene; 
 R a  at each occurrence is independently selected from hydrogen, (C 1 -C 3 )alkyl and halogen; 
 Z, Z 1  and Z 2  are each independently N or CH optionally substituted with halo, (C 1 -C 3 )alkoxy or (C 1 -C 3 )alkyl; 
 L is a direct bond, O, S, NH, N(C 1 -C 3 )alkyl or (C 1 -C 3 )alkylene; 
 R 2  is hydrogen, halo, cyano, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, where said (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl, or 5- to 6-membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, (C 1 -C 3 )alkyl, halo-substituted (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo-substituted (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkyl-S(O) n —, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkoxy, —(C 0 -C 3 )alkylNR x R y , —(C 0 -C 3 )alkylNR x C(O)R y , and —(C 0 -C 3 )alkylC(O)NR x R y ; with the proviso that when L is O, S, NH or N(C 1 -C 3 )alkyl then R 2  is not halo; 
 n at each occurrence is independently 0, 1 or 2; and 
 R x  and R y  at each occurrence are independently selected from hydrogen and (C 1 -C 6 )alkyl where said (C 1 -C 6 )alkyl is optionally interrupted with one or two groups independently selected from NH, N(C 1 -C 3 )alkyl, O and S, and is optionally substituted with 1 to 4 halo; or R x  and R y  taken together are a (C 2 -C 6 )alkylene which is optionally interrupted with one or two groups independently selected from NH, N(C 1 -C 3 )alkyl, O and S; 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The compound of  claim 1  wherein:
 R 1  is phenyl or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, where said phenyl or said 5- to 6-membered heteroaryl is optionally fused to a (C 4 -C 7 )cycloalkyl, (C 5 -C 6 )cycloalkenyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or a 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, wherein said optionally fused phenyl and said optionally fused 5- to 6-membered heteroaryl is optionally substituted with 1 to 3 substituents selected from halo, hydroxy, oxo, cyano, (C 1 -C 3 )alkyl, halo-substituted (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo-substituted (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkyl-S(O) n —, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkoxy, —(C 0 -C 3 )alkyl-NR x R y , —(C 0 -C 3 )alkyl-NR x C(O)R y , and —(C 0 -C 3 )alkyl-C(O)NR x R y ; 
 R a  at each occurrence is independently selected from hydrogen, (C 1 -C 3 )alkyl and halogen; 
 Z, Z 1  and Z 2  are each independently N or CH optionally substituted with halo, (C 1 -C 3 )alkoxy or (C 1 -C 3 )alkyl; 
 L is a direct bond, O, S, NH, N(C 1 -C 3 )alkyl or (C 1 -C 3 )alkylene; 
 R 2  is hydrogen, halo, cyano, (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl containing 1 to 4 heteroatoms each independently selected from N, O or S, or 5- to 6-membered heteroaryl containing 1 to 4 heteroatoms each independently selected from N, O, or S, where said (C 1 -C 6 )alkyl, (C 3 -C 6 )cycloalkyl, phenyl, saturated or partially unsaturated 5- to 6-membered heterocyclyl, or 5- to 6-membered heteroaryl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, (C 1 -C 3 )alkyl, halo-substituted (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, halo-substituted (C 1 -C 3 )alkoxy, (C 1 -C 3 )alkyl-S(O) n —, (C 3 -C 6 )cycloalkyl, (C 3 -C 6 )cycloalkoxy, —(C 0 -C 3 )alkylNR x R y , —(C 0 -C 3 )alkylNR x C(O)R y , and —(C 0 -C 3 )alkylC(O)NR x R y ; with the proviso that when L is O, S, NH or N(C 1 -C 3 )alkyl then R 2  is not halo; 
 n at each occurrence is independently 0, 1 or 2; and 
 R x  and R y  at each occurrence are independently selected from hydrogen and (C 1 -C 6 )alkyl where said (C 1 -C 6 )alkyl is optionally interrupted with one or two groups independently selected from NH, N(C 1 -C 3 )alkyl, O and S, and is optionally substituted with 1 to 4 halo; or R x  and R y  taken together are a (C 2 -C 6 )alkylene which is optionally interrupted with one or two groups independently selected from NH, N(C 1 -C 3 )alkyl, O and S; 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The compound of  claim 2  wherein:
 R 1  is phenyl, naphthyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, thiazolyl, oxazolyl, thiazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, 2,3-dihydrobenzofuranyl, chromanyl, 3,4-dihydro-2H-pyrano[3,2-b]pyridinyl, 2,3-dihydrofurano[3,2-b]pyridinyl, indolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, [1,2,4]triazolo[4,3-a]pyridine, imidazo[2,1-b][1,3]thiazolyl, pyridinyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-b][1,2,4]triazinyl, 1H-pyrazolo[3,4-b]pyridinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-indazolyl, pyridazinyl, oxadiazolyl or imidazo[1,2-a]pyridinyl; imidazo[1,2-b]pyridazinyl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridinyl (, each optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, trifluoromethyl, trifluoromethoxy, cyano, cyclopropyl, —C(O)NR x R y  and —(C 0 -C 1 )alkylNHC(O)CH 3 ; or a pharmaceutically acceptable salt thereof. 
 
     
     
         4 . The compound of  claim 3  wherein:
 R 1  is phenyl, imidazo[2,1-b][1,3]thiazolyl, pyridinyl, pyrazolo[1,5-a]pyridinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-indazolyl, pyridazinyl, oxadiazolyl or imidazo[1,2-a]pyridinyl, imidazo[1,2-b]pyridazinyl, 1H-pyrazolo[3,4-b]pyridinyl, imidazo[1,2-b]pyridazinyl, 2,3-dihydro[1,4]dioxino[2,3-b]pyridinyl: each optionally substituted with 1 to 3 substituents independently selected from methyl, methoxy, cyano, cyclopropyl, —C(O)NH 2  and —NHC(O)CH 3 ; 
 R a  at each occurrence is hydrogen; and 
 Z, Z 1  and Z 2  are each CH; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         5 . The compound of  claim 2  wherein
 L is a direct bond; and 
 R 2  is hydrogen, phenyl, phenoxy, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, pyridinyl, oxazolyl, oxadiazolyl, pyrazolyl, pyridazinyl, triazinyl or pyrazinyl; each optionally substituted with 1 to 3 substituents independently selected from methyl, trifluoromethyl, ethyl, methoxy, cyano or —C(O)NH 2 ; or a pharmaceutically acceptable salt thereof. 
 
     
     
         6 . The compound of  claim 2  of Formula (IA) 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The compound of  claim 6  wherein
 R 1  is phenyl, naphthyl, imidazolyl, pyrazolyl, pyrazinyl, pyrimidinyl, thiazolyl, oxazolyl, thiazolyl, benzthiazolyl, benzoxazolyl, quinolinyl, 2,3-dihydrobenzofuranyl, chromanyl, 3,4-dihydro-2H-pyrano[3,2-b]pyridinyl, 2,3-dihydrofurano[3,2-b]pyridinyl, indolyl, 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazolyl, [1,2,4]triazolo[4,3-a]pyridine, imidazo[2,1-b][1,3]thiazolyl, pyridinyl, pyrazolo[1,5-a]pyridinyl, imidazo[1,2-b][1,2,4]triazinyl, 1H-pyrazolo[3,4-b]pyridinyl, 4,5,6,7-tetrahydropyrazolo[1,5-a]pyridinyl, imidazo[2,1-b][1,3,4]thiadiazolyl, 1H-indazolyl, imidazo[1,2-b]pyridazinyl, 2,3-dihydro-[1,4]dioxino[2,3-b]pyridinyl or imidazo[1,2-a]pyridinyl; each optionally substituted with 1 to 3 substituents independently selected from fluoro, chloro, (C 1 -C 3 )alkyl, (C 1 -C 3 )alkoxy, trifluoromethyl, trifluoromethoxy, cyano, cyclopropyl, —C(O)NH 2  and —NHC(O)CH 3 ; or a pharmaceutically acceptable salt thereof. 
 
     
     
         8 . The compound of  claim 7  wherein:
 R 2  is phenyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, thiazolyl, thiadiazolyl, pyridinyl, oxazolyl, oxadiazolyl, pyrimidinyl, pyrazolyl, pyridazinyl, triazinyl or pyrazinyl each optionally substituted with 1 to 3 substituents independently selected from methyl, ethyl, methoxy, cyano or —C(O)NH 2 ; and L is a direct bond or O; or a pharmaceutically acceptable salt thereof. 
 
     
     
         9 . The compound of  claim 8  wherein
 R 2  is phenyl, pyrimidinyl, triazolyl, thiazolyl, pyridinyl, oxazolyl, pyrimidinyl, pyrazolyl, or pyrazinyl; each optionally substituted with 1 to 3 substituents independently selected from methyl, ethyl, methoxy, cyano or —C(O)NH 2 ; and L is a direct bond; or a pharmaceutically acceptable salt thereof. 
 
     
     
         10 . The compound of  claim 1  selected from the group consisting of:
 5-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrazine-2-carboxamide; 
 5-[1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrazine-2-carboxamide; 
 5-{1-[7-(imidazo[1,2-a]pyridin-2-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1H-inden-5-yl}pyrazine-2-carboxamide; 
 6-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrimidine-4-carboxamide; 
 5-[1-{7-[(5-cyclopropylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carboxamide; 
 5-[1-{7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carboxamide; 
 6-[1-{7-[(7-methyl imidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrimidine-4-carboxamide; 
 5-[1-{7-[(5-ethylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrazine-2-carboxamide; 
 6-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]nicotinamide; 
 7-[(4-methoxyphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 3-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)-1H-indazole; 
 7-[(4-methoxyphenyl)acetyl]-2-[5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(4-methoxyphenyl)acetyl]-2-[5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1,3-thiazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methyl-1,3-thiazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-(5-phenoxy-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane; 
 7-[(4-methoxyphenyl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methoxypyridin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(2-methylpyridin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-(1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl)isonicotinonitrile; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methylpyridin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methoxypyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methoxypyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(4-methylpyridin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-(5-pyrazin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane; 
 2-[5-(4,6-dimethylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methylpyridin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(5-ethylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(6-ethylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 2-(2-{2-[5-(6-ethylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-5-methoxybenzonitrile; 
 6-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrimidine-4-carbonitrile; 
 7-[(4-methoxyphenyl)acetyl]-2-[5-(1,3-oxazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-pyrimidin-4-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-cyclopropylpyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1,3-oxazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-7-{[4-(trifluoromethyl)phenyl]acetyl}-2,7-diazaspiro[3.5]nonane; 
 5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethoxy)benzonitrile; 
 2-[2,3-dihydro-1H-inden-1-yl]-7-[(4-methoxyphenyl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-cyclopropylpyridin-2-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(4,6-dimethylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)benzonitrile; 
 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(2,6-dimethylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 6-[1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrimidine-4-carbonitrile; 
 N-[5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)phenyl]acetamide; 
 7-[(2,3-dimethylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(1-ethyl-1H-pyrazol-3-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 1-methyl-3-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-1H-pyrazolo[3,4-b]pyridine; 
 1-ethyl-3-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-1H-pyrazolo[3,4-b]pyridine; 
 7-[(1-phenyl-1H-imidazol-4-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-{[5-(difluoromethyl)pyridin-2-yl]acetyl}-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(3-methyl-1H-pyrazol-5-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 6-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)imidazo[1,2-b][1,2,4]triazine; 
 6-[1-{7-[(5-cyclopropyl pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyrimidine-4-carbonitrile; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 6-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridine; 
 6-(2-{2-[5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridine; 
 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(1-methyl-1H-pyrazol-3-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)imidazo[1,2-a]pyridine; 
 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(1,3-thiazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1-methyl-1H-pyrazol-3-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 N-[5-methoxy-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)phenyl]acetamide; 
 2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)imidazo[1,2-a]pyridine; 
 6-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridine; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 6-(2-{2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridine; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(6-methoxypyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(5-ethylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(4-methoxyphenyl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 7-methyl-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)imidazo[1,2-a]pyridine; 
 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 4-[1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]benzamide; 
 5-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carbonitrile; 
 4-[1-{7-[(5-ethylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]benzamide; 
 4-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]benzamide; 
 4-{1-[7-(imidazo[1,2-a]pyridin-2-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1H-inden-5-yl}benzamide; 
 7-[(4-cyclopropylphenyl)acetyl]-2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]nonane; 
 7-[(4-cyclopropyl phenyl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-ethylpyridin-2-yl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methylpyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-ethylpyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(4-methyl phenyl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(4-ethyl phenyl)acetyl]-2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[5-(2,6-dimethylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 2-{2-oxo-2-[2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]non-7-yl]ethyl}pyrazolo[1,5-a]pyridine; 
 2-{2-oxo-2-[2-(5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl)-2,7-diazaspiro[3.5]non-7-yl]ethyl}-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine; 
 7-methyl-2-(2-oxo-2-{2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)imidazo[1,2-a]pyridine; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(4-methoxyphenyl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-ethoxypyridin-2-yl)acetyl]-2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 N-[5-methoxy-2-(2-oxo-2-{2-[5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)phenyl]acetamide; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1H-1,2,4-triazol-1-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(5-methyl-1,3,4-thiadiazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 5-methyl-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)benzamide; 
 5-methoxy-2-(2-oxo-2-{2-[5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)benzamide; 
 5-methoxy-2-(2-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)benzamide; 
 5-methoxy-2-(3-{2-[5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-3-oxopropyl)benzamide; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(4-methyl-1H-pyrazol-1-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(4-methoxyphenyl)acetyl]-2-[5-(4-methyl-1H-pyrazol-1-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[5-(1H-pyrazol-1-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 5-{1-[7-(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1H-inden-5-yl}pyridine-2-carboxamide; 
 5-[1-{7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carboxamide; 
 5-[1-{7-[(5-methylpyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carboxamide; 
 5-[1-{7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carboxamide; 
 5-{1-[7-(imidazo[1,2-a]pyridin-2-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1H-inden-5-yl}pyridine-2-carboxamide; and 
 5-[1-{7-[(7-methylimidazo[1,2-a]pyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]non-2-yl}-2,3-dihydro-1H-inden-5-yl]pyridine-2-carboxamide; 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The compound of  claim 6  selected from the group consisting of
 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(4-methoxyphenyl)acetyl]-2-[(1R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1R)-5-(1,3-thiazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[(1R)-5-(5-ethylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1R)-5-(5-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-ethylpyridin-2-yl)acetyl]-2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 7-[(5-methylpyridin-2-yl)acetyl]-2-[(1R)-5-(2H-1,2,3-triazol-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-[(1R)-5-(2,6-dimethylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-7-[(5-methoxypyridin-2-yl)acetyl]-2,7-diazaspiro[3.5]nonane; 
 7-[(2-methylimidazo[2,1-b][1,3]thiazol-6-yl)acetyl]-2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 6-(2-{2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridine; 
 5-{(1R)-1-[7-(2,3-dihydro[1,4]dioxino[2,3-b]pyridin-6-ylacetyl)-2,7-diazaspiro[3.5]non-2-yl]-2,3-dihydro-1H-inden-5-yl}pyridine-2-carboxamide; 
 7-[(5-methoxypyridin-2-yl)acetyl]-2-[(1R)-5-(4-methylpyrimidin-2-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 2-(2-{2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)imidazo[1,2-a]pyridine; 
 7-[(2-methylimidazo[2,1-b][1,3,4]thiadiazol-6-yl)acetyl]-2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]nonane; 
 5-methoxy-2-(2-oxo-2-{2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)benzamide; 
 5-methoxy-2-(2-{2-[(1R)-5-(6-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)benzamide; 
 N-[5-methoxy-2-(2-oxo-2-{2-[(1R)-5-pyrimidin-2-yl-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}ethyl)phenyl]acetamide; and 
 6-(2-{2-[(1R)-5-(2-methylpyrimidin-4-yl)-2,3-dihydro-1H-inden-1-yl]-2,7-diazaspiro[3.5]non-7-yl}-2-oxoethyl)-2,3-dihydro[1,4]dioxino[2,3-b]pyridine; 
 
       or a pharmaceutically acceptable salt thereof. 
     
     
         12 . A pharmaceutical composition comprising a compound of  claim 1  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable excipient, diluent, or carrier. 
     
     
         13 . The composition of  claim 12  wherein said compound or said therapeutically acceptable salt thereof is present in a therapeutically effective amount. 
     
     
         14 . The composition of  claim 12  further comprising at least one additional pharmaceutical agent selected from the group consisting of an anti-obesity agent, an anti-diabetic agent, a lipid lowering agent or an anti-hypertensive agent. 
     
     
         15 . The composition of  claim 14  wherein said anti-obesity agent is selected from the group consisting of dirlotapide, mitratapide, implitapide, R56918 (CAS No. 403987), CAS No. 913541-47-6, lorcaserin, cetilistat, PYY 3-36 , naltrexone, oleoyl-estrone, obinepitide, pramlintide, tesofensine, leptin, liraglutide, bromocriptine, orlistat, AOD-9604 (CAS No. 221231-10-3), sibutramine, 11β-hydroxy steroid dehydrogenase-1 (11β-HSD type 1) inhibitors, stearoyl-CoA desaturase-1 (SCD-1) inhibitor, an MCR-4 agonist, a cholecystokinin-A (CCK-A) agonist, sympathomimetic agents, β 3  adrenergic agonists, melanocyte-stimulating hormone analogs, 5HT2c agonists, a melanin concentrating hormone antagonist, leptin, a leptin analog, leptin agonists, a galanin antagonist, an anorectic agent, a neuropeptide-Y antagonist, PYY 3-36  or an analog thereof, a thyromimetic agent, dehydroepiandrosterone or an analog thereof, a glucocorticoid agonist or antagonist, an orexin antagonist, a glucagon-like peptide-1 agonist, a ciliary neurotrophic factor, a human agouti-related protein (AGRP) inhibitor, histamine 3 antagonists or inverse agonists, a neuromedin U agonist, dirlotapide, JTT130, Usistapide, SLx4090, MTP/ApoB inhibitors, a mu opioid receptor modulator, a MetAp2 inhibitor, MAR-701, ZP2929, an orexin antagonist, a combination of bupropion plus zonisamide, a combination of pramlintide plus metreleptin, a combination of bupropion plus naltrexone, and a combination of phentermine plus topiramate. 
     
     
         16 . The composition of  claim 14  wherein said anti-diabetic agent is selected from the group consisting of metformin, acetohexamide, chlorpropamide, diabinese, glibenclamide, glipizide, glyburide, glimepiride, gliclazide, glipentide, gliquidone, glisolamide, tolazamide, tolbutamide, tendamistat, trestatin, acarbose, adiposine, camiglibose, emiglitate, miglitol, voglibose, pradimicin-Q, salbostatin, balaglitazone, ciglitazone, darglitazone, englitazone, isaglitazone, pioglitazone, rosiglitazone, troglitazone, exendin-3, exendin-4, trodusquemine, reservatrol, GSK2245840, GSK184072, hyrtiosal extract, sitagliptin, vildagliptin, alogliptin, saxagliptin, dutogliptin, linagliptin, an ACC inhibitor, a DGAT-1 inhibitor, a phosphodiesterase (PDE)-10 inhibitor, an AMPK activator, a meglitinide, tendamistat, trestatin, AL-3688, CLX-0940, GW-1536, GW-1929, GW-2433, KRP-297, L-796449, LR-90, MK-0767, SB-219994, liraglutide, albiglutide, exenatide, albiglutide, taspoglutide, lixisenatide, dulaglutide, semaglutide, NN-9924, an insulin secreatagogue, a fatty acid oxidation inhibitor, an A2 antagonist, a c-jun amino-terminal kinase (JNK) inhibitor, a glucokinase activator, insulin, an insulin mimetic, a glycogen phosphorylase inhibitor, a VPAC2 receptor agonist, an SGLT2 inhibitor, a glucagon receptor modulator, a mineralocorticoid receptor inhibitor, an FGF21 derivatives or analog, a TGR5 receptor modulator, a GPR119 modulator, GPR40 agonist, a GPR120 modulator, a high affinity nicotinic acid receptor (HM74A) activator, and an SGLT1 inhibitor. 
     
     
         17 . A method for treating obesity and obesity-related disorders in animals comprising the step of administering to an animal in need of such treatment a therapeutically effective amount of a compound  claim 1  or a pharmaceutically acceptable salt thereof. 
     
     
         18 . A method for treating or delaying the progression or onset of type 2 diabetes and diabetes-related disorders in animals comprising the step of administering to an animal in need of such treatment a therapeutically effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt thereof. 
     
     
         19 . A method for treating obesity and obesity-related disorders in animals comprising the step of administering to an animal in need of such treatment a pharmaceutical composition of  claim 13 . 
     
     
         20 . A method for treating or delaying the progression or onset of type 2 diabetes and diabetes-related disorders in animals comprising the step of administering to an animal in need of such treatment a pharmaceutical composition of  claim 13 .