IP Library › Granted Patent US 8,129,376

Granted Patent B2

US 8,129,376 · App. 12/408,486 · Granted Mar 6, 2012

Piperidine derivatives as inhibitors of stearoyl-CoA desaturase

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Quick Facts

Patent No.: US 8,129,376
App. No.: 12/408,486
Granted: Mar 6, 2012
Kind: B2

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Abstract

The present invention relates to piperidine derivatives that act as inhibitors of stearoyl-CoA desaturase. The invention also relates to methods of preparing the compounds, compositions containing the compounds, and to methods of treatment using the compounds.

Claims (299)

1. A compound of the formula:

wherein

R 1 is aryl or heteroaryl;

R 2 is aryl or heteroaryl;

R 3 and R 4 are each independently hydrogen, halogen or alkyl; or

R 3 and R 4 , together with the carbon atom to which they are attached, form a cycloalkyl group;

R 5 is hydrogen or alkyl;

m and n are, independently, 1 or 2;

X is —O—, —NR 6 —, —S—, —S(O)— or —S(O) 2 — where R 6 is hydrogen or alkyl;

wherein, when present, an aryl or heteroaryl group may optionally be substituted by one or more halogen, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino, arylamino, diarylamino, amido, alkylamido, carboxyl, alkyl, halogenated alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocycle, heterocyclealkyl, aroyl, acyl, alkoxy, aryloxy, heteroaryloxy, cycloalkyloxy, cycloalkylalkyloxy, arylalkyloxy, heteroarylalkyloxy, alkylthio, arylthio, alkylsulfinyl, alkylsulfonyl, arylsulfinyl, arylsulfonyl, heteroarylsulfinyl, heteroarylsulfonyl alkoxycarbonyl, aryloxycarbonyl or heteroaryloxycarbonyl, and combinations thereof;

and pharmaceutically acceptable salts, or enantiomer or diastereomer thereof;

with the proviso that said compound is not

4-[[(2R)-2,3-dihydro-2-methyl-6-nitroimidazo[2,1-b]oxazol-2-yl]methoxy]-N-[2-oxo-2-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl]ethyl]-benzamide,

N-[2-[4-[[4-amino-5-(2,6-difluorobenzoyl)-2-thiazolyl]amino]-1-piperidinyl]-2-oxoethyl]-M-methyl-benzamide,

4-amino-N-[2-[4-[[4-amino-5-(2,6-difluorobenzoyl)-2-thiazolyl]amino]-1-piperidinyl]-2-oxoethyl]-benzamide,

or a pharmaceutically acceptable salt thereof.

2. The compound of claim 1 , wherein R1 is aryl that is substituted by one or more aryl groups.

3. The compound of claim 1 , wherein R1 is heteroaryl and is substituted by one or more aryl or heteroaryl groups.

4. The compound of claim 1 , wherein R1 is pyrazole, triazole, or isoxazole.

5. The compound of claim 1 , wherein R2 is aryl.

6. The compound of claim 1 , wherein the compound is selected from:

1-Cyclopentyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide;

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-cyano-2-methyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide;

1-Morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide;

1-Morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide;

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(2,5-difluoro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide;

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide; and

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

7. The compound of claim 1 , wherein the compound is selected from:

Biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

Biphenyl-4-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

Biphenyl-4-carboxylic acid {2-[4-(2-bromo-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

Biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

Biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenylamino)-piperidin-1-yl]-ethyl}-amide,

Biphenyl-4-carboxylic acid (2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide,

Biphenyl-4-carboxylic acid (2-{4-[(2-chloro-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide,

Biphenyl-4-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide,

5-Phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-isoxazole-3-carboxylic acid {2-[4-(2-bromo-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-isoxazole-3-carboxylic acid (2-{4-[(2-bromo-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide,

5-Phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenylamino)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-isoxazole-3-carboxylic acid (2-{-4-[methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide,

N-{2-oxo-2-[4-(2-trifluoromethyl-phenylamino)-piperidin-1-yl]-ethyl}-4-phenylamino-benzamide,

N-{2-[4-(2-Chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-4-phenylamino-benzamide

N-{2-[4-(2-Bromo-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-4-phenylamino-benzamide

N-(2-{4-[Methyl-(2-trifluoromethyl-phenyl)-amino]-piperidin-1-yl}-2-oxo-ethyl)-4-phenylamino-benzamide,

N-{2-[4-(2-Bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-4-phenylamino-benzamide

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-bromo-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-bromo-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenylsulfanyl)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chlorophenylsulfanyl)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-nitro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-amino-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,3-dimethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide, and

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,4-dimethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

8. The compound of claim 1 , wherein the compound is selected from:

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-dimethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-tert-butyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-bromo-phenylsulfanyl)-piperidin-1-yl]-2-oxo-ethyl}

5-Phenyl-1H-pyrazole-3-carboxylic acid [2-oxo-2-(4-o-tolylamino-piperidin-1-yl)-ethyl]-amide,

5-(3-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-pyridine-2-carboxylic acid {2-oxo-2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-pyridine-2-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(4-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Hydroxy-phenyl)-1-methyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

Synthesis of 5-(2-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

N-{2-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide,

N-{2-[4-(2-Chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-6-phenylamino-nicotinamide,

5-Phenylamino-pyridine-2-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-bromo-2-methoxy-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-cyano-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2,4-difluoro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(4-fluoro-2-trifluoromethyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-acetyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-cyano-2-methyl-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzenesulfinyl)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(pyridin-4-yloxy)-piperidin-1-yl]-ethyl}-amide, and

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

9. The compound of claim 1 , wherein the compound is selected from:

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-hydroxy-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzenesulfonyl)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(6-chloro-pyridin-2-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

4-Methyl-3-(1-{2-[(5-phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperidin-4-yloxy)-benzoic acid methyl ester,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(3-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(3-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(3-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(4-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(3-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

3-(1-{2-[(5-Phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperidin-4-yloxy)-benzoic acid,

5-(3-Fluoro-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid [2-oxo-2-(4-m-tolyloxy-piperidin-1-yl)-ethyl]-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-methyl-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Pyridin-2-yl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

3-(5-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethylcarbamoyl}-1H-pyrazol-3-yl)-benzoic acid,

5-Pyridin-3-yl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-Pyridin-3-yl-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(4-methyl-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(5-trifluoromethyl-pyridin-3-yloxy)-piperidin-1-yl]-ethyl}-amide,

5-(5-Chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(5-Chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide, and

5-(2-Hydroxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

10. The compound of claim 1 , wherein the compound is selected from:

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-methanesulfonyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(2-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(2-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(3-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Hydroxy-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(3-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-(4-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(4-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(2-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(3-Fluoro-phenyl)-isoxazole-3-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-pyrazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

2-[(Biphenyl-4-ylmethyl)-amino]-1-[4-(2-chloro-phenoxy)-piperidin-1-yl]-ethanone,

N-{2-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-4-[1,3,4]oxadiazol-2-yl-benzamide,

4-Phenyl-pyrazole-1-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-(3-Fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-(3-Fluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide

1-m-Tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-m-Tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-(2-Cyano-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-o-Tolyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Cyclopentyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-(5-Fluoro-pyridin-3-yl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

N-{2-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-4-(5-methyl-[1,3,4]oxadiazol-2-yl)-benzamide, and

3′-Dimethylamino-biphenyl-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

11. The compound of claim 1 , wherein the compound is selected from:

N-{2-Oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-4-(pyrrolidine-1-carbonyl)-benzamide,

9H-Carbazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-formyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

2-(1-{2-[(5-Phenyl-1H-pyrazole-3-carbonyl)-amino]-acetyl}-piperidin-4-yloxy)-benzoic acid,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-hydroxymethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3,4,5-trifluoro-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid (2-{4-[2-(hydroxyimino-methyl)-phenoxy]-piperidin-1-yl}-2-oxo-ethyl)-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(3-cyano-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid (2-{4-[2-(methoxyimino-methyl)-phenoxy]-piperidin-1-yl}-2-oxo-ethyl)-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-methylcarbamoyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(2-carbamoyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Trifluoromethyl-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(3-cyano-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(adamantan-2-ylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-(2-Methoxy-phenyl)-1H-pyrazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyrrolidin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-(1-Methyl-pyrrolidin-3-yl)-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-(3,5-Difluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-(3,5-Difluoro-phenyl)-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-chloro-pyridin-3-yloxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Piperidin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide hydrochloride,

1-(1-Methyl-piperidin-4-yl)-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-cyano-2-methyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[3-(3-trifluoromethyl-phenoxy)-pyrrolidin-1-yl]-ethyl}-amide,

4-(2-Oxo-pyrrolidin-1-yl)-N-{2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-benzamide,

1-Cyclopropyl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide, and

1-Morpholin-4-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

12. The compound of claim 1 , wherein the compound is selected from:

1-Phenyl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(3-cyano-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(2,5-difluoro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[3-(3-trifluoromethyl-phenoxy)-azetidin-1-yl]-ethyl}-amide,

5-Pyridin-3-yl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[3-(3-trifluoromethyl-phenoxy)-azetidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(2,5-difluoro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(5-cyano-2-methyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(4-fluoro-3-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-isoxazole-3-carboxylic acid {2-[3-(2,5-difluoro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide,

2-Phenyl-4H-thieno[3,2-b]pyrrole-5-carboxylic acid {2-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

6-Pyrazol-1-yl-imidazo[1,2-a]pyridine-2-carboxylic acid {2-[4-(2-chloro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(3-cyano-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-pyrrolidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(4-fluoro-3-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(3-fluoro-5-trifluoromethyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(3-fluoro-5-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[4-(4-fluoro-3-trifluoromethyl-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide,

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(2-chloro-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide, and

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-[3-(5-cyano-2-methyl-phenoxy)-azetidin-1-yl]-2-oxo-ethyl}-amide,

and pharmaceutically acceptable salts thereof.

13. A compound of the formula:

wherein

R 1 is heteroaryl;

R 2 is aryl or heteroaryl;

R 3 and R 4 are each independently hydrogen, halogen or alkyl; or

R 3 and R 4 , together with the carbon atom to which they are attached, form a cycloalkyl group;

R 5 is hydrogen or alkyl;

m and n are, independently, 1 or 2;

X is —O—, —NR 6 —, —S—, —S(O)— or —S(O) 2 — where R 6 is hydrogen or alkyl;

and pharmaceutically acceptable salts or enantiomer or diastereomer thereof.

14. A compound of the formula:

wherein

R 1 is aryl or heteroaryl;

R 2 is aryl or heteroaryl;

R 3 and R 4 are each independently hydrogen, halogen or alkyl; or

R 3 and R 4 , together with the carbon atom to which they are attached, form a cycloalkyl group;

R 5 is hydrogen or alkyl;

X is —O—, —NR 6 —, —S—, —S(O)— or —S(O) 2 — where R 6 is hydrogen or alkyl;

and pharmaceutically acceptable salts thereof;

with the proviso that said compound is not

4-[[(2R)-2,3-dihydro-2-methyl-6-nitroimidazo[2,1-b]oxazol-2-yl]methoxy]-N-[2-oxo-2-[4-[4-(trifluoromethoxy)phenoxy]-1-piperidinyl]ethyl]-benzamide,

N-[2-[4-[[4-amino-5-(2,6-difluorobenzoyl)-2-thiazolyl]amino]-1-piperidinyl]-2-oxoethyl]-M-methyl-benzamide,

4-amino-N-[2-[4-[[4-amino-5-(2,6-difluorobenzoyl)-2-thiazolyl]amino]-1-piperidinyl]-2-oxoethyl]-benzamide,

or a pharmaceutically acceptable salt thereof.

15. A compound of the formula:

wherein

R 7 is aryl or heteroaryl;

R 8 is aryl or heteroaryl;

R 9 and R 10 are each independently hydrogen, halogen or alkyl; or

R 9 and R 10 , together with the carbon atom to which they are attached, form a cycloalkyl group;

R 11 is hydrogen or alkyl;

X is —O—, —NR 12 —, —S—, —S(O)— or —S(O) 2 — where R 12 is hydrogen or alkyl;

16. The compound of claim 1 , wherein the compound is selected from:

N-Biphenyl-4-yl-3-[4-(2-bromo-phenoxy)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2-chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2-bromo-phenylamino)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2-bromo-phenylsulfanyl)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-oxo-3-(4-o-tolylamino-piperidin-1-yl)-propionamide,

N-Biphenyl-4-yl-3-[4-(2-nitro-phenoxy)-piperidin-1-yl]-3-oxo-propionamide,

3-[4-(2-Amino-phenoxy)-piperidin-1-yl]-N-biphenyl-4-yl-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2,3-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2,4-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2,5-dimethyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2-tert-butyl-phenylamino)-piperidin-1-yl]-3-oxo-propionamide,

N-Biphenyl-4-yl-3-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-3-oxo-propionamide,

Synthesis of 3-[4-(2-Chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide,

3-[4-(2-Chloro-5-fluoro-phenoxy)-piperidin-1-yl]-3-oxo-N-(5-phenyl-pyridin-2-yl)-propionamide,

3-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide,

3-[4-(2-Chloro-phenylamino)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide,

3-[4-(2-Bromo-phenylamino)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide,

3-Oxo-N-(6-phenyl-pyridin-3-yl)-3-[4-(2-trifluoromethyl-phenylamino)-piperidin-1-yl]-propionamide,

3-[4-(2-Chloro-phenylsulfanyl)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide,

3-[4-(2-Bromo-phenylsulfanyl)-piperidin-1-yl]-3-oxo-N-(6-phenyl-pyridin-3-yl)-propionamide,

3-Oxo-N-(6-phenyl-pyridin-3-yl)-3-[4-(2-trifluoromethyl-phenylsulfanyl)-piperidin-1-yl]-propionamide,

3-Oxo-N-(6-phenyl-pyridin-3-yl)-3-[4-(2-trifluoromethyl-phenoxy)-piperidin-1-yl]-propionamide,

3-Oxo-N-(6-phenyl-pyridin-3-yl)-3-(4-o-tolylamino-piperidin-1-yl)-propionamide,

3-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-3-oxo-N-(3-phenyl-[1,2,4]thiadiazol-5-yl)-propionamide,

3-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-N-(4-[1,2,4]oxadiazol-3-yl-phenyl)-3-oxo-propionamide,

3-[4-(2-Chloro-phenoxy)-piperidin-1-yl]-3-oxo-N-(5-phenyl-thiazol-2-yl)-propionamide,

3-[4-(2-Chloro-phenylamino)-piperidin-1-yl]-3-oxo-N-(5-phenyl-thiazol-2-yl)-propionamide,

1-[4-(2-Chloro-phenoxy)-piperidine-1-carbonyl]-cyclopropane carboxylic acid biphenyl-4-ylamide,

N-Biphenyl-4-yl-3-oxo-3-[4-(3,4,5-trifluoro-phenoxy)-piperidin-1-yl]-propionamide, and

N-Biphenyl-4-yl-3-[4-(3-cyano-phenoxy)-piperidin-1-yl]-3-oxo-propionamide,

and pharmaceutically acceptable salts thereof.

17. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.

18. The compound of claim 1 , wherein the compound is:

Biphenyl-4-carboxylic acid (2-{4-[methyl-(2-trifluoromethyl-phenyl)-amino ]-piperidin-1-yl}-2-oxo-ethyl)-amide or a pharmaceutically acceptable salt thereof.

19. The compound of claim 1 , wherein the compound is:

5-Phenyl-isoxazole-3-carboxylic acid {2-[4-(2-chloro-phenylamino)-piperidin-1-yl]-2-oxo-ethyl}-amide or a pharmaceutically acceptable salt thereof.

20. The compound of claim 1 , wherein the compound is:

5-Phenyl-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide or a pharmaceutically acceptable salt thereof

21. The compound of claim 1 , wherein the compound is:

1-Pyridin-3-yl-1H-[1,2,3]triazole-4-carboxylic acid {2-[4-(5-cyano-2-methyl-phenoxy) -piperidin-1-yl]-2-oxo-ethyl}-amide or a pharmaceutically acceptable salt thereof.

22. The compound of claim 1 , wherein the compound is:

1-Phenyl-1H-imidazole-4-carboxylic acid {2-[4-(2,5-difluoro-phenoxy)-piperidin-1-yl]-2-oxo-ethyl}-amide or a pharmaceutically acceptable salt thereof.

Assignments (3)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 4, 2009

From: SUNDARESAN, KUMAR; KOTESWARA RAO, P. BALA; AINAN, BHARATHIRAJA; AYYAMPERUMAL, HARIHARASUBRAMANIAN; A R, GIRISH; TATIPARTHY, SRINIVAS; PRABHU, GANESH; SUBRAMANYA, HOSAHALLI S.

To: AURIGENE DISCOVERY TECHNOLOGIES LIMITED

Reel/Frame 022780/0850 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 4, 2009

From: BISCHOFF, ALEXANDER

To: FOREST LABORATORIES HOLDINGS LIMITED

Reel/Frame 022781/0209 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 4, 2009

From: AURIGENE DISCOVERY TECHNOLOGIES LIMITED

To: FOREST LABORATORIES HOLDINGS LIMITED

Reel/Frame 022781/0265 →

Priority Claims (1)

IN 575/KOL/2008 · Mar 20, 2008 · national

Continuity (2)

Provisional Application 61049480 · May 1, 2008

Related Publication 20090239810A1 · Sep 24, 2009