MAGL inhibitors

JP7856644B2Active Publication Date: 2026-05-11H LUNDBECK AS
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Patent Information

Authority / Receiving Office
JP · JP
Patent Type
Patents
Current Assignee / Owner
H LUNDBECK AS
Filing Date
2021-11-12
Publication Date
2026-05-11

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Benefits of technology

を有してもよいことが提言されている。したがって、本明細書に開示される一実施形態では、気分及び不安障害の治療に使用するための、式(I)、(Ia)、(Ib)、(Ic)、(Id)、(Ie)、又は(If)の化合物又はその薬学的に許容可能な塩が提供される。

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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 containing the compounds. The compounds and compositions provided herein are useful as inhibitors of MAGL. Furthermore, the compounds and compositions provided herein are useful for treating diseases and disorders that benefit from inhibition of MAGL.
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Claims

1. Equation (I): 【Chemistry 1】 (In the formula, R1 is -C(O)NHR2, -C(O)N(CH ３ )R2, -C(O)NR3R4, -C(O)NHCH ２ Represents R2, or -C(O)NHC(O)R2; R2 is a phenyl or a five- or six-membered heteroaryl having one or two heteroatoms independently selected from N, O, and S, a six-membered heterocycle having one or two heteroatoms independently selected from N or O, C ３ ~C ７ Represents a cycloalkyl or a seven-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 bonded, form a nine-membered or ten-membered bicyclic heterocycle having one to four heteroatoms independently selected from N or O, or a six-membered heterocycle having one or two heteroatoms independently selected from N or O; Each phenyl, 5- or 6-membered heteroaryl, 6-membered heterocyclic ring, C ３ -C ７ ycloalkyl, 7-membered bicyclic heterocyclic ring, or 9- or 10-membered bicyclic heterocyclic ring is unsubstituted or is substituted by one or two substituents independently selected from halogen, C １ -C ３ alkyl, C １ -C ３ haloalkyl, C ３ -C ６ ycloalkyl, C １ -C ３ alkoxy, cyano, -NHC(O)CH ３ , -C(O)NH ２ , -C(O)NHCH ３ , 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. Equation (Ia): 【Chemistry 2】 (In the formula, R1 is -C(O)NHR2, -C(O)N(CH ３ )R2, -C(O)NR3R4, -C(O)NHCH ２ Represents R2, or -C(O)NHC(O)R2; R2 is a phenyl or a five- or six-membered heteroaryl having one or two heteroatoms independently selected from N, O, and S, a six-membered heterocycle having one or two heteroatoms independently selected from N or O, C ３ ~C ７ Represents a cycloalkyl or a seven-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 bonded, form a nine-membered or ten-membered bicyclic heterocycle having one to four heteroatoms independently selected from N or O, or a six-membered heterocycle having one or two heteroatoms independently selected from N or O; Each phenyl, 5-membered or 6-membered heteroaryl, 6-membered heterocycle, C ３ ~C ７ Cycloalkyl, 7-membered bicyclic heterocycle, or 9-membered or 10-membered bicyclic heterocycle is unsubstituted, or contains halogens, 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 five-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 The compound according to claim 1 or a pharmaceutically acceptable salt thereof, having a structure (substituted by one or two substituents independently selected from the COOH group).

3. A compound according to any one of claims 1 to 2, or a pharmaceutically acceptable salt thereof, wherein R1 represents -C(O)NHR2.

4. R2 represents a 5-membered or 6-membered heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyridadinyl, pyrimidyl, pyrazolyl, thiazolyl, and isoxazolyl, wherein the 5-membered or 6-membered heteroaryl is unsubstituted, or contains a 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 five-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 A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, substituted with one substituent selected from the group consisting of COOH.

5. R2 represents a six-membered heterocycle selected from the group consisting of tetrahydro-2H-pyran-4-yl, piperazinyl, and piperidinyl, and R2 is either unsubstituted or C １ ~C ３ Alkyl, C ３ ~C ６ A compound according to any one of claims 1 to 3, or a pharmaceutically acceptable salt thereof, substituted with one substituent selected from the group consisting of cycloalkyl and cyano.

6. The compound according to any one of claims 1 to 5 or a pharmaceutically acceptable salt thereof, wherein R2 represents a six-membered heterocycle selected from the group consisting of tetrahydro-2H-pyran-4-yl, piperazinyl, and piperidinyl, and R2 is unsubstituted.

7. Formula (Ic): 【Transformation 3】 (In the formula, R5 is a 5-membered or 6-membered heteroaryl, 6-membered heterocycle, C, having one or two heteroatoms independently selected from phenyl, N, O, and S. ３ ~C ７ Represents a cycloalkyl or a seven-membered bicyclic heterocycle having one or two heteroatoms independently selected from N or O; R6 represents hydrogen or methyl; W is -CH ２ - or -C(O)-; n is either 0 or 1; Each phenyl, 5-membered or 6-membered heteroaryl, 6-membered heterocycle, C ３ ~C ７ Cycloalkyl and 7-membered bicyclic heterocycles are either unsubstituted or contain halogens and 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 five-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 A compound according to any one of claims 1 to 2, or a pharmaceutically acceptable salt thereof, having a structure (substituted by one or two substituents independently selected from the COOH group).

8. A compound according to claim 7 or a pharmaceutically acceptable salt thereof, wherein n is 0.

9. R5 represents a 5- or 6-membered heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyridazinyl, pyrimidyl, pyrazolyl, thiazolyl, and isoxazolyl, and the 5- or 6-membered heteroaryl is unsubstituted or halogen, C １ ~C ３ alkyl, C １ ~C ３ haloalkyl, cyclopropyl, C １ ~C ３ alkoxy, cyano, -NH C(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, the compound according to any one of claims 7 to 8 or a pharmaceutically acceptable salt thereof.

10. The compound according to any one of claims 7 to 9 or a pharmaceutically acceptable salt thereof, wherein R5 represents a six-membered heteroaryl selected from the group consisting of pyridyl, pyrazinyl, pyridadinyl, and pyrimidyl, and the six-membered heteroaryl is unsubstituted.

11. R5 represents a six-membered heterocycle selected from the group consisting of tetrahydro-2H-pyran-4-yl, piperazinyl, and piperidinyl, and R5 is either unsubstituted or C １ ~C ３ Alkyl, C ３ ~C ６ A compound according to any one of claims 7 to 8, or a pharmaceutically acceptable salt thereof, substituted with one substituent selected from the group consisting of cycloalkyl and cyano.

12. A compound according to any one of claims 7 to 11, or a pharmaceutically acceptable salt thereof, wherein R5 is unsubstituted.

13. 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(pyridine-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(pyridazine-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(pyrazine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(isoxazole-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((2-(trifluoromethyl)pyrimidine-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-(dimethylphosphoryl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(pyridine-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-pyrazole-1-yl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-(methylcarbamoyl)pyridine-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-methoxypyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((5-fluoropyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(methyl(pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(methyl(pyridine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(pyridine-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-(pyrazine-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-chloropyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((2-methylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-(trifluoromethyl)pyridine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(((6-(trifluoromethyl)pyridine-2-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-(trifluoromethyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-methylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((2-(trifluoromethyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((pyridine-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-(pyrimidine-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((2-(trifluoromethyl)pyrimidine-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((2-methylpyrimidine-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-methylpyridazine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(pyridazine-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((5-methylpyrazine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((1-methylpiperidine-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-pyrazole-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(thiazole-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-pyrazole-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(thiazole-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-((pyrimidine-5-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((pyridazine-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-cyclopropylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-isopropoxypyridine-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-acetamidopyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-carbamoylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-(isoxazole-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(±)1-((6-(methylsulfonamide)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; (±) 2-((5-(6-(((1,1,1,3,3,3-hexafluoropropane-2-yl)oxy)carbonyl)-6-azaspiro[2.5]octan-1-carboxamide)pyridine-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-cyanopyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate A compound according to claim 1, or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

14. 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(pyridine-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyridine-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(pyridazine-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyridazine-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(pyrazine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(methyl(pyrazine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(isoxazole-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(isoxazole-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((2-(trifluoromethyl)pyrimidine-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((2-(trifluoromethyl)pyrimidine-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-(dimethylphosphoryl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-(dimethylphosphoryl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(pyridine-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyridine-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-pyrazole-1-yl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-(1H-pyrazole-1-yl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-(methylcarbamoyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-(methylcarbamoyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-methoxypyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-methoxypyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((5-fluoropyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((5-fluoropyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(methyl(pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(methyl(pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(methyl(pyridine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(methyl(pyridine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(pyridine-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyridine-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-(pyrazine-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyrazine-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-chloropyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((5-chloropyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((2-methylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((2-methylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-(trifluoromethyl)pyridine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-(trifluoromethyl)pyridine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(((6-(trifluoromethyl)pyridine-2-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(((6-(trifluoromethyl)pyridine-2-yl)methyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-(trifluoromethyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-(trifluoromethyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-methylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-methylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((2-(trifluoromethyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((2-(trifluoromethyl)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((pyridine-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((pyridine-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-(pyrimidine-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyrimidine-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((2-(trifluoromethyl)pyrimidine-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((2-(trifluoromethyl)pyrimidine-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((2-methylpyrimidine-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((2-methylpyrimidine-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-methylpyridazine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-methylpyridazine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(pyridazine-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(pyridazine-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((5-methylpyrazine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((5-methylpyrazine-2-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((1-methylpiperidine-4-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((1-methylpiperidine-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-pyrazole-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((1-methyl-1H-pyrazole-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(thiazole-5-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(thiazole-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-pyrazole-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((1-methyl-1H-pyrazole-5-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(thiazole-2-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(thiazole-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-((pyrimidine-5-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((pyrimidine-5-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((pyridazine-3-ylmethyl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((pyridazine-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-cyclopropylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-cyclopropylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-isopropoxypyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-isopropoxypyridine-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-acetamidopyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-acetamidopyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-carbamoylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-carbamoylpyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-(isoxazole-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-(isoxazole-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(R)-1-((6-(methylsulfonamide)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; 1,1,1,3,3,3-Hexafluoropropan-2-yl(S)-1-((6-(methylsulfonamide)pyridine-3-yl)carbamoyl)-6-azaspiro[2.5]octane-6-carboxylate; (R)-2-((5-(6-(((1,1,1,3,3,3-hexafluoropropane-2-yl)oxy)carbonyl)-6-azaspiro[2.5]octan-1-carboxamide)pyridine-2-yl)oxy)acetic acid; and (S)-2-((5-(6-(((1,1,1,3,3,3-hexafluoropropane-2-yl)oxy)carbonyl)-6-azaspiro[2.5]octan-1-carboxamide)pyridine-2-yl)oxy)acetic acid A compound according to claim 1 or a pharmaceutically acceptable salt thereof, selected from the group consisting of the following.

15. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, is 1,1,1,3,3,3-hexafluoropropan-2-yl(S)-1-(pyridine-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate.

16. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, is 1,1,1,3,3,3-hexafluoropropan-2-yl(S)-1-(pyridazine-3-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate.

17. The compound according to claim 1, or a pharmaceutically acceptable salt thereof, is 1,1,1,3,3,3-hexafluoropropan-2-yl(S)-1-(isoxazole-4-ylcarbamoyl)-6-azaspiro[2.5]octane-6-carboxylate.