Magl inhibitors

Abstract

Provided herein are substituted 1,1,1,3,3,3-hexafluoropropan-2-yl 6-azaspiro[2.5]octane-6-carboxylate compounds and pharmaceutical compositions comprising said compounds. The compounds and compositions provided herein are useful as inhibitors of MAGL. Furthermore, the compounds and compositions as provided herein are useful for the treatment of diseases and disorders benefiting from the inhibition of MAGL.

1 . A compound of Formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R1 represents —C(O)NHR2, —C(O)N(CH 3 )R2, —C(O)NR3R4, —C(O)NHCH 2 R2, or —C(O)NHC(O)R2; 
         R2 represents a phenyl, a 5 or 6 membered heteroaryl having one or two heteroatoms independently selected from N, O and S, a 6 membered heterocycle having one or two heteroatoms independently selected from N or O, a C 3 -C 7  cycloalkyl, or a 7 membered bicyclic heterocycle having one or two heteroatoms independently selected from N or O; 
         R3 and R4 together with the N to which they are attached form a 9 or 10 membered bicyclic heterocycle having 1 to 4 heteroatoms independently selected from N or O, or a 6 membered heterocycle having one or two heteroatoms independently selected from N or O; and 
         wherein each phenyl, 5 or 6 membered heteroaryl, 6 membered heterocycle, C 3 -C 7  cycloalkyl, 7 membered bicyclic heterocycle, or 9 or 10 membered bicyclic heterocycle are unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, C 3 -C 6  cycloalkyl, C 1 -C 3  alkoxy, cyano, —NHC(O)CH 3 , —C(O)NH 2 , —C(O)NHCH 3 , a 5 membered heteroaryl having one or two heteroatoms independently selected from N or O, —NHSO 2 CH 3 , —P(O)(CH 3 ) 2 , and —OCH 2 COOH; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 . The compound according to  claim 1  having the structure of Formula (Ia): 
       
         
           
           
               
               
           
         
         wherein:
 R1 represents —C(O)NHR2, —C(O)N(CH 3 )R2, —C(O)NR3R4, —C(O)NHCH 2 R2, or —C(O)NHC(O)R2; 
 R2 represents a phenyl, a 5 or 6 membered heteroaryl having one or two heteroatoms independently selected from N, O and S, a 6 membered heterocycle having one or two heteroatoms independently selected from N or O, a C 3 -C 7  cycloalkyl, or a 7 membered bicyclic heterocycle having one or two heteroatoms independently selected from N or O; 
 R3 and R4 together with the N to which they are attached form a 9 or 10 membered bicyclic heterocycle having 1 to 4 heteroatoms independently selected from N or O, or a 6 membered heterocycle having one or two heteroatoms independently selected from N or O; and 
 wherein each phenyl, 5 or 6 membered heteroaryl, 6 membered heterocycle, C 3 -C 7  cycloalkyl, 7 membered bicyclic heterocycle, or 9 or 10 membered bicyclic heterocycle are unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, C 3 -C 6  cycloalkyl, C 1 -C 3  alkoxy, cyano, —NHC(O)CH 3 , —C(O)NH 2 , —C(O)NHCH 3 , a 5 membered heteroaryl having one or two heteroatoms independently selected from N or O, —NHSO 2 CH 3 , —P(O)(CH 3 ) 2 , and —OCH 2 COOH; 
 or a pharmaceutically acceptable salt thereof. 
 
       
     
     
         3 . The compound according to any one of  claims 1 - 2 , or a pharmaceutically acceptable salt thereof, wherein R1 represents —C(O)NHR2. 
     
     
         4 . The compound according to any one of  claims 1 - 3  or a pharmaceutically acceptable salt thereof, wherein R2 represents a 5 or 6 membered heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, pyrazolyl, thiazolyl, and isoxazolyl, wherein said 5 or 6 membered heteroaryl is unsubstituted or substituted with 1 substituent selected from the group consisting of halogen, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, cyclopropyl, C 1 -C 3  alkoxy, cyano, —NHC(O)CH 3 , —C(O)NH 2 , —C(O)NHCH 3 , a 5 membered heteroaryl having 1 or 2 heteroatoms selected independently from N or O, —NHSO 2 CH 3 , —P(O)(CH 3 ) 2 , and —OCH 2 COOH. 
     
     
         5 . The compound according to any one of  claims 1 - 3 , or a pharmaceutically acceptable salt thereof, wherein R2 represents a 6 membered heterocycle selected from the group consisting of tetrahydro-2H-pyran-4-yl, piperazinyl, and piperidinyl, wherein said R2 is unsubstituted or substituted with 1 substituent selected from the group consisting of C 1 -C 3  alkyl, C 3 -C 6  cycloalkyl, and cyano. 
     
     
         6 . The compound according to any one of  claims 1 - 5 , or a pharmaceutically acceptable salt thereof, wherein R2 represents a 6 membered heterocycle selected from the group consisting of tetrahydro-2H-pyran-4-yl, piperazinyl, and piperidinyl, wherein said R2 is unsubstituted. 
     
     
         7 . The compound according to any one of  claims 1 - 2 , or a pharmaceutically acceptable salt thereof having the structure of Formula (Ic): 
       
         
           
           
               
               
           
         
         wherein: 
         R5 represents a phenyl, a 5 or 6 membered heteroaryl having one or two heteroatoms independently selected from N, O and S, a 6 membered heterocycle, a C 3 -C 7  cycloalkyl, or a 7 membered bicyclic heterocycle having one or two heteroatoms independently selected from N or O; 
         R6 represents a hydrogen or methyl; 
         W is —CH 2 — or —C(O)—; 
         n is 0 or 1; and 
         wherein each phenyl, 5 or 6 membered heteroaryl, 6 membered heterocycle, C 3 -C 7  cycloalkyl, 7 membered bicyclic heterocycle are unsubstituted or substituted with 1 or 2 substituents independently selected from halogen, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, C 3 -C 6  cycloalkyl, C 1 -C 3  alkoxy, cyano, —NHC(O)CH 3 , —C(O)NH 2 , —C(O)NHCH 3 , a 5 membered heteroaryl having one or two heteroatoms independently selected from N or O, —NHSO 2 CH 3 , —P(O)(CH 3 ) 2 , and —OCH 2 COOH; 
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         8 . The compound according to  claim 7  or a pharmaceutically acceptable salt thereof, wherein n is 0. 
     
     
         9 . The compound according to any one of  claims 7 - 8 , or a pharmaceutically acceptable salt thereof, wherein R5 represents a 5 or 6 membered heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, pyrazolyl, thiazolyl, and isoxazolyl, wherein said 5 or 6 membered heteroaryl is unsubstituted or substituted with 1 substituent selected from the group consisting of halogen, C 1 -C 3  alkyl, C 1 -C 3  haloalkyl, cyclopropyl, C 1 -C 3  alkoxy, cyano, —NHC(O)CH 3 , —C(O)NH 2 , —C(O)NHCH 3 , a 5 membered heteroaryl having one or two heteroatoms independently selected from N or O, —NHSO 2 CH 3 , —P(O)(CH 3 ) 2 , and —OCH 2 COOH. 
     
     
         10 . The compound according to any one of  claims 7 - 9 , or a pharmaceutically acceptable salt thereof, wherein R5 represents a 6 membered heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyridazinyl, and pyrimidyl, wherein said 6 membered heteroaryl is unsubstituted. 
     
     
         11 . The compound according to any one of  claims 7 - 8 , or a pharmaceutically acceptable salt thereof, wherein R5 represents a 6 membered heterocycle selected from the group consisting of tetrahydro-2H-pyran-4-yl, piperazinyl, and piperidinyl, wherein said R5 is unsubstituted or substituted with 1 substituent selected from the group consisting of C 1 -C 3  alkyl, C 3 -C 6  cycloalkyl, and cyano. 
     
     
         12 . The compound according to any one of  claims 7 - 11 , or a pharmaceutically acceptable salt thereof, wherein R5 is unsubstituted. 
     
     
         13 . A compound according to  claim 1 , wherein the compound is selected from the group consisting of:
 1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyridin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyridazin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((tetrahydro-2H-pyran-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(methyl(pyrazin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(isoxazol-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((2-(trifluoromethyl)pyrimidin-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-(dimethylphosphoryl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyridin-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((tetrahydro-2H-pyran-4-carbonyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-(1H-pyrazol-1-yl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-(methylcarbamoyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(4-cyclopropylpiperazine-1-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-methoxypyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((5-fluoropyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(methyl(pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(methyl(pyridin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyridin-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyrazin-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(2-cyclopropyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((5-chloropyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((2-methylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-(trifluoromethyl)pyridin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(((6-(trifluoromethyl)pyridin-2-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-(trifluoromethyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-methylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((2-(trifluoromethyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((pyridin-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((cyclohexanecarbonyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(benzoylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyrimidin-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((2-(trifluoromethyl)pyrimidin-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((2-methylpyrimidin-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-methylpyridazin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(pyridazin-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((5-methylpyrazin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((1-methylpiperidin-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(morpholine-4-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(4-cyanopiperidine-1-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((1-methyl-1H-pyrazol-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(thiazol-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((4-methyltetrahydro-2H-pyran-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((1-methyl-1H-pyrazol-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(thiazol-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(phenylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(p-tolylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)-1-((3-fluorophenyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate:   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(benzylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((pyrimidin-5-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((pyridazin-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((2-oxaspiro[3.3]heptan-6-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-cyclopropylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-isopropoxypyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-acetamidopyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-carbamoylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(isoxazol-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-(methylsulfonamido)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   (±)2-((5-(6-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)-6-azaspiro[2.5]octane-1-carboxamido)pyridin-2-yl)oxy)acetic acid;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(3-cyclopropyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-(methyl(pyridazin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; and   1,1,1,3,3,3-hexafluoropropan-2-yl (±)1-((6-cyanopyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; or a pharmaceutically acceptable salt thereof.   
     
     
         14 . The compound according to  claim 1 , wherein the compound is selected from the group consisting of:
 1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyridin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate 1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyridin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyridazin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate 1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyridazin-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((tetrahydro-2H-pyran-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((tetrahydro-2H-pyran-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(methyl(pyrazin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(methyl(pyrazin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(isoxazol-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(isoxazol-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((2-(trifluoromethyl)pyrimidin-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((2-(trifluoromethyl)pyrimidin-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-(dimethylphosphoryl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-(dimethylphosphoryl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyridin-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyridin-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((tetrahydro-2H-pyran-4-carbonyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((tetrahydro-2H-pyran-4-carbonyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-(1H-pyrazol-1-yl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-(1H-pyrazol-1-yl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-(methylcarbamoyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-(methylcarbamoyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-methoxypyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-methoxypyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((5-fluoropyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((5-fluoropyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(methyl(pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(methyl(pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(methyl(pyridin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(methyl(pyridin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyridin-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyridin-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(2-(trifluoromethyl)-5,6,7,8-tetrahydroimidazo[1,2-a]pyrazine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyrazin-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyrazin-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(2-(trifluoromethyl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine-7-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(2-cyclopropyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(2-cyclopropyl-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine-6-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((5-chloropyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((5-chloropyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((2-methylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((2-methylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-(trifluoromethyl)pyridin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-(trifluoromethyl)pyridin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(((6-(trifluoromethyl)pyridin-2-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(((6-(trifluoromethyl)pyridin-2-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-(trifluoromethyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-(trifluoromethyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-methylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-methylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((2-(trifluoromethyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((2-(trifluoromethyl)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((pyridin-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((pyridin-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((cyclohexanecarbonyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((cyclohexanecarbonyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(benzoylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(benzoylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyrimidin-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyrimidin-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((2-(trifluoromethyl)pyrimidin-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((2-(trifluoromethyl)pyrimidin-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((2-methylpyrimidin-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((2-methylpyrimidin-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-methylpyridazin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-methylpyridazin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(pyridazin-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(pyridazin-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((5-methylpyrazin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((5-methylpyrazin-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((1-methylpiperidin-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((1-methylpiperidin-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(((tetrahydro-2H-pyran-4-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(morpholine-4-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(morpholine-4-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(4-cyanopiperidine-1-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(4-cyanopiperidine-1-carbonyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((1-methyl-1H-pyrazol-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((1-methyl-1H-pyrazol-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(thiazol-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(thiazol-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((4-methyltetrahydro-2H-pyran-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((4-methyltetrahydro-2H-pyran-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((1-methyl-1H-pyrazol-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((1-methyl-1H-pyrazol-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(thiazol-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(thiazol-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(phenylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(phenylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(p-tolylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(p-tolylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((3-fluorophenyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((3-fluorophenyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(benzylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(benzylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((pyrimidin-5-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((pyrimidin-5-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((pyridazin-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((pyridazin-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((2-oxaspiro[3.3]heptan-6-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((2-oxaspiro[3.3]heptan-6-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-cyclopropylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-cyclopropylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-isopropoxypyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-isopropoxypyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(((4-methyltetrahydro-2H-pyran-4-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-acetamidopyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-acetamidopyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-carbamoylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-carbamoylpyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-(isoxazol-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-(isoxazol-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (R)-1-((6-(methylsulfonamido)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   1,1,1,3,3,3-hexafluoropropan-2-yl (S)-1-((6-(methylsulfonamido)pyridin-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate;   (R)-2-((5-(6-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)-6-azaspiro[2.5]octane-1-carboxamido)pyridin-2-yl)oxy)acetic acid; and   (S)-2-((5-(6-(((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)carbonyl)-6-azaspiro[2.5]octane-1-carboxamido)pyridin-2-yl)oxy)acetic acid; or a pharmaceutically acceptable salt thereof.   
     
     
         15 . A pharmaceutical composition comprising a compound according to any one of the previous  claims 1  to  14 , or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers or diluents. 
     
     
         16 . A compound according to any one of  claims 1  to  14 , or a pharmaceutically acceptable salt thereof, for use as a medicament. 
     
     
         17 . A compound according to any one of  claims 1  to  14 , or a pharmaceutically acceptable salt thereof, for use in the treatment of a disease or disorder selected from the group consisting of: pain, epilepsy/seizure disorder, Alzheimer's disease, Huntington's chorea, Huntington's disease, spacsticity, multiple sclerosis, obsessive-compulsive disorder, Parkinson's disease, depression, post-traumatic stress disorder, generalized anxiety disorder, and dystonia. 
     
     
         18 . Use of a compound according to any one of  claims 1  to  14 , or a pharmaceutically acceptable salt thereof, in the manufacture of a medicament for the treatment of a disease or disorder selected from the group consisting of: pain, epilepsy/seizure disorder, Alzheimer's disease, Huntington's chorea, Huntington's disease, spacsticity, multiple sclerosis, obsessive-compulsive disorder, Parkinson's disease, depression, post-traumatic stress disorder, generalized anxiety disorder, and dystonia. 
     
     
         19 . A method for the treatment of a disease or disorder selected from the group consisting of: pain, epilepsy/seizure disorder, Alzheimer's disease, Huntington's chorea, Huntington's disease, spacsticity, multiple sclerosis, obsessive-compulsive disorder, Parkinson's disease, depression, post-traumatic stress disorder, generalized anxiety disorder, and dystonia comprising the administration of a therapeutically effective amount of a compound according to any one of  claims 1  to  14 , or a pharmaceutically acceptable salt thereof to a patient in need thereof.