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US 2014/0194424 A1Published application
Spirolactam derivatives and uses of same
AssigneeH. Lundbeck A/S
InventorsHao Zhou, Guiying Li, Dario Doller, Gil Ma
Life of this patent
Estimating the term…
Abstract
The present invention provides spirolactam derivatives of formula (I): wherein R1-R7 are as defined herein; or a pharmaceutically acceptable salt thereof; and pharmaceutical compositions and uses of the same.
Claims19
1-20. (canceled)
A method of treating a disease or disorder comprising administering a therapeutically effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof wherein the disease or disorder is a central nervous system disease or disorder;
- and
- wherein:
- R1 and R2 are each independently aryl, heteroaryl, alkyl, cycloalkyl, ketocycloalkyl, or heterocyclyl, which is optionally mono-, di-, or tri-substituted independently with alkyl, cycloalkyl, alkoxy, hydroxy, halogen, cyano, trifluoroalkyl, amino, acyl, aryl, heteroaryl, heterocyclyl, —C(O)NHR30, —C(O)N(R30)R31—N(R30)C(O)R31, —NHR30, —N(R30)R31 or —OR30;
- wherein:
- R30 and R31 are each independently C1-C6alkyl or C1-C6cycloalkyl that is optionally substituted with acyl, halogen, —CN, —NH2, —NH(C1-C3alkyl), —N(C1-C3alkyl)2, C1-C3alkylheterocyclyl, C1-C3alkylcarbamate, —C(O)NH(C1-C3alkyl), —C(O)N(C1-C3alkyl)2, —NHC(O)—C1-C3alkyl, —N(C1-C3alkyl)-C(O)—C1-C3alkyl, OH, or —O—C1-C6alkyl;
- and
- each aryl, heteroaryl, heterocyclyl substituent is optionally substituted with C1-3alkyl, C3-5cycloalkyl, C1-3alkoxy, hydroxy, halogen, cyano, trifluoroalkyl, or amino;
- R3, R4, R5 and R6 are each independently H, C1-3alkyl, C3-5cycloalkyl, halogen, or hydroxy;
- R7 is H;
- or
- R1 and R7 taken together with the —C(O)N— to which they are attached form a mono- or bicyclic 4- to 12-membered heterocycloalkyl or heteroaryl, which optionally contains 1-3 additional heteroatoms;
- or a pharmaceutically acceptable salt thereof.
9 more elements
The method of claim 20, wherein R1 and R2 are both aryl.
The method of claim 20, wherein R1 and R2 are both heteroaryl.
The method of claim 20, wherein R1 is aryl and R2 is heteroaryl.
The method of claim 20, wherein R1 is heteroaryl and R2 is aryl.
The method of claim 20, wherein either R1 or R2 is heteroaryl
The method of claim 20, wherein either R1 or R2 is aryl.
The method of claim 20, wherein at least one aryl is phenyl.
The method of claim 20, wherein R1 is aryl or heteroaryl and R2 is cycloalkyl, ketocycloalkyl or heterocyclyl.
The method of claim 20, wherein the mono-, di-, or tri-substituents are independently selected from the group consisting of methyl, methoxy, dimethylamino-ethoxy, amino, methylamino, dimethylamino, cyano, chloro, cyano, dimethylamino, dimethylamino-ethoxy, methyl, methylamino, methoxy, fluoro, —C(O)NHCH3, phenyl, furanyl, pyrrolidinyl, thiophenyl and trifluoromethyl.
The method of claim 20, wherein the phenyl is optionally substituted with fluorine.
The method of claim 20, wherein the compound is selected from the group consisting of trans-Pyridine-2-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-6-Methyl-pyridine-2-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5R,7R)-2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5S,7S)-2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(6-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 3-Chloro-N-[2-(6-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-Pyridine-2-carboxylic acid [2-(3-cyano-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3-cyano-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyrazine-2-carboxylic acid [2-(3-cyano-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyrazine-2-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyrazine-2-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-1-Methyl-1H-pyrazole-3-carboxylic acid [2-(3-chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[2-(3-Cyano-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- cis-N-[2-(3-Cyano-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-chloro-benzamide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-6-Methyl-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-Pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyrazine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-6-Methyl-pyrazine-2-carboxylic acid[2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(6-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-3-Fluoro-N-[2-(6-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- Pyridine-2-carboxylic acid [(5R,7R)-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 3-Fluoro-N-(1-oxo-2-pyridin-2-yl-2-aza-spiro[4.5]dec-7-yl)-benzamide;
- cis-3-Fluoro-N-[2-(6-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- 3-Fluoro-N-[(5R,7R)-2-(6-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-Pyridine-2-carboxylic acid [2-(4-methyl-pyrimidin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(4-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(4-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(4-methyl-pyrimidin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-3-Fluoro-N-[2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-[2-(4-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-[2-(4-methyl-pyrimidin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-[2-(6-methyl-pyrazin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-Pyridine-2-carboxylic acid [2-(6-methyl-pyrazin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(6-methyl-pyrazin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [1-oxo-2-(6-trifluoromethyl-pyridin-2-yl)-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(6-cyano-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 6-Methyl-pyridine-2-carboxylic acid (1-oxo-2-pyridin-2-yl-2-aza-spiro[4.5]dec-7-yl)-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid (1-oxo-2-phenyl-2-aza-spiro[4.5]dec-7-yl)-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid (1-oxo-2-m-tolyl-2-aza-spiro[4.5]dec-7-yl)-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(4-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(5-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3-methyl-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(2-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(2-methyl-pyridin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[2-(6-Cyano-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- cis-Pyridine-2-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyrazine-2-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyrazine-2-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-3-Chloro-N-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(6-methyl-pyrazin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(3-cyano-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [1-oxo-2-(6-trifluoromethyl-pyridin-2-yl)-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(6-methyl-pyridin-3-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(5-fluoro-pyridin-3-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-3-Fluoro-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-[2-(2-methyl-pyridin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- 6-Methyl-pyridine-2-carboxylic acid [(5R,7R)-2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-5-Fluoro-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyrimidine-4-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(5-methyl-pyridin-3-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3-methoxy-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 6-Methyl-pyridine-2-carboxylic acid [(5R,7R)-2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(5-fluoro-pyridin-3-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(3,4-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[2-(3-Fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-isonicotinamide;
- cis-N-[2-(3-Fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-2-methyl isonicotinamide;
- cis-Pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-azaspiro[4.5]dec-7-yl]-amide;
- 6-Methyl-pyridine-2-carboxylic acid [(5R,7R)-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 6-Methyl-pyridine-2-carboxylic acid [(5S,7S)-2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [(5R,7R)-2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid (2-benzyl-1-oxo-2-aza-spiro[4.5]dec-7-yl)-amide;
- cis-3-Methyl-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3,5-Difluoro-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-6-Methyl-pyrazine-2-carboxylic acid {2-[6-(4-fluoro-phenyl)-pyrimidin-4-yl]-1-oxo-2-aza-spiro[4.5]dec-7-yl}-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid {2-[6-(4-fluoro-phenyl)-pyrimidin-4-yl]-1-oxo-2-aza-spiro[4.5]dec-7-yl}-amide;
- cis-3-Fluoro-N-{2-[6-(4-fluoro-phenyl)-pyrimidin-4-yl]-1-oxo-2-aza-spiro[4.5]dec-7-yl}-benzamide;
- cis-4-Fluoro-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3,4-Difluoro-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-2-Fluoro-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-2-Methyl-N-[2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-isonicotinamide;
- cis-6-Hydroxymethyl-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Trifluoromethyl-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- N-[(5R,7R)-2-(3-Fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-2-methyl-isonicotinamide;
- cis-6-Trifluoromethyl-pyridine-2-carboxylic acid [2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5R,7S)-9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5S,7R)-9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- or
- cis-2-[2-(3-Chloro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-2,3-dihydro-isoindol-1-one;
- Pyridine-2-carboxylic acid [(5S,7S)-9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5R,7R)-9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [(5S,7R)-9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [(5R,7S)-9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-9,9-difluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [9,9-difluoro-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [9,9-difluoro-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-6-Methyl-pyridine-2-carboxylic acid [9,9-difluoro-2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [2-(3,5-difluoro-phenyl)-9,9-difluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [9,9-difluoro-2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pyridine-2-carboxylic acid [9,9-difluoro-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5S,7R)-2-(3,5-difluoro-phenyl)-9,9-difluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [(5R,7S)-2-(3,5-difluoro-phenyl)-9,9-difluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1,9-dioxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-9-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-9-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [(5R,7S,9S)-2-(3,5-difluoro-phenyl)-9-hydroxy-9-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [(5R,7S,9R)-2-(3,5-difluoro-phenyl)-9-hydroxy-9-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- N-[(5S,7R)-9,9-Difluoro-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- N-[(5R,7S)-9,9-Difluoro-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- trans-2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-9-fluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-3-Fluoro-N-[2-(3-fluoro-phenyl)-1,9-dioxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-6-Methyl-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-1,9-dioxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- trans-3-Fluoro-N-[2-(3-fluoro-phenyl)-9-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- trans-6-Methyl-pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-9-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 6-Methyl-pyridine-2-carboxylic acid [(5S,7R)-9,9-difluoro-2-(5-fluoro-pyridin-2-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[9,9-Difluoro-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [9,9-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-azaspiro[4.5]dec-7-yl]-amide;
- cis 3-Fluoro-N-[-2-(3-methoxy-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis 3-Fluoro-N-[2-(3-hydroxy-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-N-[(5S,7S)-2-(3-Dimethylamino-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- cis-3-Fluoro-N-[(2-(4-methoxy-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-{2-[3-(3-morpholin-4-yl-propyl)-phenyl]-1-oxo-2-aza-spiro[4.5]dec-7-yl}-benzamide;
- cis-3-Fluoro-N-[2-(3-fluoro-5-methoxy-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-{1-oxo-2-[3-(2-oxo-2-pyrrolidin-1-yl-ethoxy)-phenyl]-2-aza-spiro[4.5]dec-7-yl}-benzamide;
- cis-Thiazole-2-carboxylic acid [2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[2-(4-Dimethylamino-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- cis-3-Fluoro-N-(1-oxo-2-thiazol-2-yl-2-aza-spiro[4.5]dec-7-yl)-benzamide;
- cis-Thiazole-2-carboxylic acid [(2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-pyrimidine-4-carboxylic acid [2-(3-fluoro-5-methoxy-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[2-(3-Cyano-5-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- cis-Thiazole-2-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-2-Methyl-thiazole-4-carboxylic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-Pentanoic acid [2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-N-[2-(3,5-Difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-butyramide;
- 3-Fluoro-N-[(5R,7R)-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- 3-Chloro-N-[(5R,7R)-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-5-Fluoro-pyridine-2-carboxylic acid [(2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- cis-3-Fluoro-N-[1-oxo-2-(2-trifluoromethyl-pyrimidin-4-yl)-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-N-[2-(2,6-Dimethyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-3-fluoro-benzamide;
- 3-Methyl-N-[(5R,7R)-2-(2-methyl-pyrimidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- cis-3-Fluoro-N-(2-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl)-benzamide;
- cis-3-Fluoro-N-(2-ethyl-1-oxo-2-aza-spiro[4.5]dec-7-yl)-benzamide;
- cis-3-Fluoro-N-(2-propyl-1-oxo-2-aza-spiro[4.5]dec-7-yl)-benzamide;
- 6-Methyl-pyridine-2-carboxylic acid[(5R,7R)-1-oxo-2-(2-trifluoromethyl-pyrimidin-4-yl)-2-aza-spiro[4.5]dec-7-yl]-amide;
- 3-Fluoro-N-[2-(1-methyl-piperidin-4-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- 3-Fluoro-N-[2-(1-methyl-1H-pyrazol-3-yl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-benzamide;
- and
- 2-Methyl-6-oxo-1,6-dihydro-pyrimidine-4-carboxylic acid [(5R,7R)-2-(3,5-difluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]amide;
- or a pharmaceutically acceptable salt thereof.
158 more elements
The method of claim 1, wherein the compound is selected from the group consisting of Pyridine-2-carboxylic acid [9-fluoro-2-(3-fluoro-phenyl)-9-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-9-fluoro-9-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [9-fluoro-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [8,8-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [8-fluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-8-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [8-fluoro-2-(3-fluoro-phenyl)-8-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-8-hydroxy-8-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-8,8-difluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-8-fluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-8-fluoro-8-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-8-hydroxy-8-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-8-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [8,8-difluoro-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [8-fluoro-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [8-fluoro-2-(4-fluoro-phenyl)-8-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(4-fluoro-phenyl)-8-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(4-fluoro-phenyl)-8-hydroxy-8-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [4,4-difluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [4-fluoro-2-(3-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-4-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [4-fluoro-2-(3-fluoro-phenyl)-4-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- Pyridine-2-carboxylic acid [2-(3-fluoro-phenyl)-4-hydroxy-4-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-4,4-difluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-4-fluoro-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-4-fluoro-4-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-4-hydroxy-4-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(3,5-difluoro-phenyl)-4-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [4,4-difluoro-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [4-fluoro-2-(4-fluoro-phenyl)-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [4-fluoro-2-(4-fluoro-phenyl)-4-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(4-fluoro-phenyl)-4-hydroxy-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- and
- 2-Methyl-pyrimidine-4-carboxylic acid [2-(4-fluoro-phenyl)-4-hydroxy-4-methyl-1-oxo-2-aza-spiro[4.5]dec-7-yl]-amide;
- or a pharmaceutically acceptable salt thereof.
31 more elements
The method of claim 20, wherein the mammal is a human.
The method of claim 20, wherein the central nervous system disease or disorder is a cognitive, neurodegenerative, psychiatric or neurological disease or disorder.
The method of treating gastroesophageal reflux comprising administering a therapeutically effective amount of the compound of claim 20 or a pharmaceutically acceptable salt thereof.
The method of treating alcohol dependence comprising administering a therapeutically effective amount of the compound of claim 20 or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.