Novel pyridine derivatives

Abstract

The invention relates to a compound of formula (I) wherein R 1 to R 4 are defined as in the description and in the claims. The compound of formula (I) can be used as a medicament.

1 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R 1  is selected from the group consisting of: cycloalkyl, cycloalkylalkoxy, haloalkoxy, alkoxyalkoxy, phenyl, halophenyl, haloalkylphenyl, phenylalkyl, halophenylalkyl, phenylhydroxyalkyl, phenyloxyalkyl, phenylalkoxy, alkoxyphenyl, halophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, 3-alkoxy-azetidinyl, tetrahydropyranylalkyl, tetrahydropyranylalkoxy, tetrahydrothiopyranyl 1,1-dioxide, 1,1-dioxo-[1,2]thiazinan-4-yl, piperidin-2-onyl, tetrahydrofuranylalkoxy, pyridinylalkoxy, alkyloxetanylalkoxy, hydroxylhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfonyl, alkylsulfanyl and (halo)(haloalkyl)phenyl; 
         R 2  is selected from the group consisting of: hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkoxy, haloalkoxy, alkylamino, haloalkylamino, tetrahydropyranyl, 1H-pyrazolyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, oxopyrrolidinyl, haloazetidinyl, hydroxyazetidinyl, 1,1-dioxido-2-isothioazolidinyl, tetrahydrofuranyl, cycloalkylamino, hydroxyoxetanyl, alkylsulfonyl, oxetanyl, 6oxa-1-aza-spiro[3.3]heptyl, 3,3-difluoro-2-oxo-azetidinyl, oxo-azetidinyl and oxo-pyrrolidinyl; 
         or R 1  and R 2  together with the ring to which they are attached form tetrahydroquinolinyl or alkyltetrahydroquinolinyl; 
         one of R 3  and R 4  is hydrogen and the other one is —(CR 5 R 6 ) m (CR 7 R 8 ) n —R 9 ; 
         or R 3  and R 4  together with the nitrogen atom to which they are attached form piperidinyl, 1,1-dioxidotetrahydro-2H-thiopyranyl, thiomorpholinyl, 2-oxa-6-aza-spiro[3.3]heptyl or 1-hydroxyalkylpyrrolidinyl; 
         R 5  and R 6  are each independently selected from the group consisting of: hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, phenyl, pyridazinyl, halophenyl, pyrimidinyl, alkylsulfanylalkyl and alkylsulfonylalkyl; 
         or R 5  and R 6  together with the carbon atom to which they are attached form cycloalkyl, tetrahydropyranyl or oxetanyl; 
         R 7  and R 8  are each independently selected from the group consisting of: hydrogen, alkyl and cycloalkyl; 
         R 9  is selected from the group consisting of: alkyl, hydroxyl, cyano, carboxyl, alkoxycarbonyl, alkyl[1,2,4]oxadiazolyl, oxazolyl, thiazolyl, [1,3,4]oxadiazolyl, cycloalkyl, phenyl, pyridinyl, tetrahydropyranyl, alkyl[1,2,4]thiadiazolyl, [1,2,4]thiadiazolyl, alkylaminocarbonyl, alkyltetrahydropyranyl, alkylisoxazolyl, aminocarbonyl, morpholinyl, dihydro-oxazolyl, [1,2,4]oxadiazolyl, hydroxycycloalkyl, alkoxycarbonylcycloalkyl, alkoxyalkoxy, hydroxyalkylcycloalkyl, alkoxypyridinyl, piperidinyl, hydroxypiperidinyl, hydroxyalkylpiperidinyl, isoxazolyl, azetidine-carbonyl, alkoxyalkylaminocarbonyl, cycloalkyl-alkylaminocarbonyl, haloazetidinylcarbonyl, alkyloxopyrrolidinyl, 1,1-dioxo-tetrahydro-1λ6-thiophenyl, 1,1-dioxo-tetrahydro-1λ6-thiophenylamino, amino[1,2,4]oxadiazolyl, 4-alkyl-5-oxo-4,5-dihydro-[1,2,4]oxadiazolyl, nitro-benzo[1,2,5]oxadiazolyl, alkylsulfonyl, alkyl[1,2,4]thiazolyl, hydroxyalkylaminocarbonyl, oxotetrahydrofuranyl, (cycloalkylalkyl)(alkoxycarbonyl)amino, 2-oxo-[1,3]oxazinanyl, haloalkyl and hydroxypyrrolidinylaminocarbonyl; 
         m is 0 or 1; and 
         n is 0, 1 or 2; 
         or a pharmaceutically acceptable salt or ester thereof. 
       
     
     
         2 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of: cycloalkyl, cycloalkylalkoxy, haloalkoxy, alkoxyalkoxy, phenyl, halophenyl, haloalkylphenyl, halophenylalkyl, halophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, tetrahydropyranylalkoxy, tetrahydrofuranylalkoxy, pyridinylalkoxy, hydroxyhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfanyl and alkylsulfonyl. 
     
     
         3 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of: cycloalkyl, cycloalkylalkoxy, haloalkoxy, alkoxyalkoxy, hdophenyl, halophenylalkyl, alkoxyphenyl, halophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, tetrahydropyranylalkoxy tetrahydrofuranylalkoxy, hydroxyhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfanyl and alkylsulfonyl. 
     
     
         4 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of: cycloalkylalkoxy, halophenyl, halophenylalkyl, tetrahydropyranylalkoxy, tetrahydrofuranylalkoxy, haloalkoxy, hydroxylhaloalkyloxy, halophenylhydroxyalkyl, alkylsulfanyl and alkylsulfonyl. 
     
     
         5 . A compound according to  claim 1 , wherein R 1  is selected from the group consisting of: cyclopropylmethoxy, chlorophenyl, fluorophenylmethyl, fluorochlorophenyl, tetrahydropyranylmethoxy, tetrahydrofuranylmethoxy, pentafluoropopyloxy, trifluorohydroxybutyloxy, fluorophenylhydroxymethyl, butylsulfanyl and butylsulfonyl. 
     
     
         6 . A compound according to  claim 1 , wherein R 2  is selected from the group consisting of: hydrogen, halogen, alkyl, haloalkyl, cycloalkyl, hydroxycycloalkyl, alkoxy haloalkylamino, tetrahydropyranyl, 1H-pyrazolyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, oxopyrrolidinyl, haloazetidinyl, hydroxyazetidinyl, 1,1-dioxido-2-isothioazolidinyl, tetrahydrofuranyl, cycloalkylamino, hydroxyoxetanyl and 6oxa-1-aza-spiro[3.3]heptyl. 
     
     
         7 . A compound according to  claim 1 , wherein R 2  is selected from the group consisting of: hydrogen, alkyl, haloalkyl, cycloalkyl, haloalkylamino, tetrahydropyranyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, haloazetidinyl, tetrahydrofuranyl, cycloalkylamino and 6-oxa-1-aza-spiro[3.3]heptyl. 
     
     
         8 . A compound according to  claim 1 , wherein R 2  is selected from the group consisting of: hydrogen, methyl, trifluoromethyl, cyclopropyl, cyclopentyl, bis(trifluoroethyl)amino, tetrahydropyranyl, pyrrolidinyl, methylpyrrolidinyl, difluoropyrrolidinyl, difluoroazetidinyl, tetrahydrofuranyl, cyclopropylamino and 6oxa-1-aza-spiro[3.3]heptyl. 
     
     
         9 . A compound according to  claim 1 , wherein R 1  and R 2  together with the ring to which they are attached form dimethyltetrahydroquinolinyl. 
     
     
         10 . A compound according to  claim 1 , wherein R 5  and R 6  are each independently selected from the group consisting of: hydrogen, methyl, ethyl, propyl, butyl, pentyl, trifluoromethyl, cyclopropyl, cyclopropylmethyl, phenyl, fluorophenyl and pyridazinyl or R 5  and R 6  together with the carbon atom to which they are attached form cyclobutyl, tetrahydropyranyl or cyclopropyl. 
     
     
         11 . A compound according to  claim 1 , wherein R 7  and R 8  are each independently selected from hydrogen and methyl. 
     
     
         12 . A compound according to  claim 1 , wherein R 9  is selected from the group consisting of: hydroxyl, cyano, carboxyl, alkoxycarbonyl, alkyl[1,2,4]oxadiazolyl, oxazolyl, thiazolyl, [1,3,4]oxadiazolyl, cycloalkyl, phenyl, pyridinyl, tetrahydropyranyl, alkyl[1,2,4]thiadiazolyl, alkylaminocarbonyl, alkyltetrahydropyranyl, alkylisoxazolyl, aminocarbonyl, morpholinyl, dihydro-oxazolyl, [1,2,4]oxadiazolyl, hydroxycycloalkyl, alkoxycarbonylcycloalkyl, alkoxyalkoxy, hydroxyalkylcycloalkyl, piperidinyl, haloazetidinylcarbonyl, nitro-benzo[1,2,5]oxadiazolyl and alkyl. 
     
     
         13 . A compound according to  claim 1 , wherein R 9  is selected from the group consisting of: hydroxyl, carboxyl, alkyl[1,2,4]oxadiazolyl, thiazolyl, alkylaminocarbonyl, aminocarbonyl, morpholinyl, alkoxyalkoxy, piperidinyl, cyano, pyridinyl, haloazetidinylcarbonyl, nitro-benzo[1,2,5]oxadiazolyl, alkoxycarbonyl and alkyl. 
     
     
         14 . A compound according to  claim 1 , wherein R 9  is selected from the group consisting of: hydroxyl, methyl[1,2,4]oxadiazolyl, thiazolyl, methylaminocarbonyl, aminocarbonyl, morpholinyl, methoxymethoxy, piperidinyl, cyano, pyridinyl, nitro benzo[1,2,5]oxadiazolyl, dimethylaminocarbonyl, methoxycarbonyl, N-methyl-N-ethylaminocarbonyl, difluoroazetidinylcarbonyl and methyl. 
     
     
         15 . (canceled) 
     
     
         16 . A compound according to  claim 1  selected from the group consisting of:
 6-Cyclopropylmethoxy-5-(tetrahydro-pyran-4-yl)-pyridine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-(3-Chloro-phenyl)-pyridine-2-carboxylic acid piperidin-1-ylamide; 
 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid ((S)-1-hydroxymethyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(2-methyl-pyrrolidin-1-yl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid (1,1-dimethyl-3-morpholin-4-yl-propyl)-amide; 
 5-Cyclopentyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (1-methyl-1-methylcarbamoyl-ethyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide; 
 5-Cyclopentyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(S)-2-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-methyl-pyridine-2-carboxylic acid ((S)-3-methyl-1-thiazol-2-yl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-pyrrolidin-1-yl)-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((S)-1-carbamoyl-2-cyclopropyl-ethyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-2-cyclopropyl-ethyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-pyrrolidin-1-yl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-2-cyclopropyl-ethyl)-amide; 
 6-Cyclopropylmethoxy-5-(tetrahydro-furan-3-yl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(tetrahydro-furan-2-yl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(tetrahydro-furan-2-yl)-pyridine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 5-Cyclopropylamino-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid ((S)-1-cyclopropylmethyl-2-hydroxy-2-methyl-propyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid ((S)-2-cyclopropyl-1-thiazol-2-yl-ethyl)-amide; 
 5-Cyclopropyl-6-(4-fluoro-benzyl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid [(S)-2-cyclopropyl-1-(2-methoxy-ethoxymethyl)-ethyl]-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(S)-2-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 5-[Bis-(2,2,2-trifluoro-ethyl)-amino]-6-cyclopropylmethoxy-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 (S)-5-Cyclopropyl-6-(cyclopropylmethoxy)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)picolinamide; 
 (S)-N-(2-amino-2-oxo-1-phenylethyl)-5-cyclopropyl-6-(cyclopropylmethoxy)picolinamide; 
 N-((S)-1-amino-4-methyl-1-oxopentan-2-yl)-5-cyclopropyl-6-((tetrahydrofuran-2-yl)methoxy)picolinamide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((R)-1-hydroxymethyl-1,2-dimethyl-propyl)-amide; 
 (S)-5-Cyclopropyl-N-(4,4-dimethyl-1-(methylamino)-1-oxopentan-2-yl)-6-((tetrahydro-2H-pyran-4-yl)methoxy)picolinamide; 
 (+)-5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(SR)-cyclopropyl-(5-methyl-[1,2,4]oxadiazol-3-yl)-methyl]-amide; 
 2-(6-(Cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)picolinamido)-2-ethylbutanoic acid; 
 (S)-6-(3-Chloro-4-fluorophenyl)-N-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)picolinamide; 
 5-Cyclopropyl-6-(tetrahydro-pyran-4-ylmethoxy)-pyridine-2-carboxylic acid [cyclopropyl-(5-methyl-[1,2,4]oxadiazol-3-yl)-methyl]-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((S)-2-cyclopropyl-1-dimethylcarbamoyl-ethyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((+)-dimethylcarbamoyl-phenyl-methyl)-amide; 
 6-Cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid ((S)-3,3-dimethyl-1-methylcarbamoyl-butyl)-amide; 
 6-(3-Chloro-4-fluoro-phenyl)-pyridine-2-carboxylic acid [cyclopropyl-(5-methyl-[1,2,4]oxadiazol-3-yl)-methyl]-amide; 
 2-{[5-Cyclopropyl-6-(tetrahydro-furan-2-ylmethoxy)-pyridine-2-carbonyl]-amino}-2-ethyl-butyric acid methyl ester; 
 6-Cyclopropylmethoxy-5-(6-oxa-1-aza-spiro[3.3]hept-1-yl)-pyridine-2-carboxylic acid ((S)-3,3-dimethyl-1-methylcarbamoyl-butyl)-amide; 
 2-Ethyl-2-{[6-(tetrahydro-pyran-4-ylmethoxy)-5-trifluoromethyl-pyridine-2-carbonyl]-amino}-butyric acid methyl ester; 
 (S)-2-[(5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carbonyl)-amino]-3,3-dimethyl-butyric acid methyl ester; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(+)-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-butyl]-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((−)-1-cyano-3-methyl-butyl)-amide; 
 (S)-3-Cyclopropyl-2-[(5-cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carbonyl)-amino]-propionic acid methyl ester; 
 6-Cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 6-(3-Chloro-4-fluoro-phenyl)-pyridine-2-carboxylic acid [1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (1-hydroxymethyl-1,3-dimethyl-butyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [1-ethyl-1-(ethyl-methyl-carbamoyl)-propyl]-amide; 
 6-(4-Fluoro-benzyl)-pyridine-2-carboxylic acid ((R)-2,2,2-trifluoro-1-pyridin-2-yl-ethyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((S)-1-hydroxymethyl-1,2-dimethyl-propyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [1-(3,3-difluoro-azetidine-1-carbonyl)-1-ethyl-propyl]-amide; 
 5-Cyclopropyl-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 5-Cyclopropyl-6-(2,2,3,3,3-pentafluoro-propoxy)-pyridine-2-carboxylic acid ((S)-3,3-dimethyl-1-methylcarbamoyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid [1-(3,3-difluoro-azetidine-1-carbonyl)-1-ethyi-propyl]-amide; 
 5-Cyclopropyl-6-((R)-4,4,4-trifluoro-3-hydroxy-butoxy)-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 6-Cyclopropylmethoxy-5-trifluoromethyl-pyridine-2-carboxylic acid [1-(3,3-difluoro-azetidine-1-carbonyl)-1-ethyl-propyl]-amide; 
 6-[(4-Fluoro-phenyl)-hydroxy-methyl]-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 5-Cyclopropyl-6-((S)-4,4,4-trifluoro-3-hydroxy-butoxy)-pyridine-2-carboxylic acid (1-ethyl-1-methylcarbamoyl-propyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(+)-1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (3-methyl-1-pyridin-3-yl-butyl)-amide; 
 5-Cyclopropyl-6-(4-fluoro-benzyl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-2-cyclopropyl-ethyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(S)-carbamoyl-(4-fluoro-phenyl)-methyl]-amide; 
 5-Cyclopropyl-6-(4-fluoro-benzyl)-pyridine-2-carboxylic acid ((S)-2,2,2-trifluoro-1-pyridin-2-yl-ethyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid [2-cyclopropyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-(3-Chloro-4-fluoro-phenyl)-pyridine-2-carboxylic acid [(S)-2-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid {(S)-3-methyl-1-[(7-nitro-benzo[1,2,5]oxadiazol-4-ylamino)-methyl]-butyl}-amide; 
 5-Cyclopropyl-6-isobutylsulfanyl-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 5-Cyclopropyl-6-(2-methyl-propane-1-sulfonyl)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid [1-methyl-1-(5-methyl-thiazol-2-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid ((R)-3-methyl-1-pyridazin-3-yl-butyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(+)-2-cyclopropyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid [(−)-2-cyclopropyl-1-methyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid tert-butylamide; 
 5-Cyclopropyl-6-(2-methyl-propane-1-sulfonyl)-pyridine-2-carboxylic acid ((S)-2,2,2-trifluoro-1-pyridin-3-yl-ethyl)-amide; 
 5-Cyclopropyl-6-cyclopropylmethoxy-pyridine-2-carboxylic acid ((+)-carbamoyl-cyclopropyl-methyl)-amide; 
 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (1-trifluoromethyl-cyclopropyl)-amide; and 
 (+)-5-Cyclopropyl-6-(2-methyl-propane-1-sulfonyl)-pyridine-2-carboxylic acid [1-cyclopropyl-1-(5-methyl-[1,2,4]oxadiazol-3-yl)-ethyl]-amide. 
 
     
     
         17 . A pharmaceutical composition comprising a compound according to  claim 1  and a therapeutically inert carrier. 
     
     
         18 . A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . A compound of formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         when R 1  is cycloalkylalkoxy, 
         R 2  is selected from the group consisting of: hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, cycloalkyl, hydroxycycloalkyl, alkoxy, haloalkoxy, alkylamino, haloalkylamino, tetrahydropyranyl, 1H-pyrazolyl, pyrrolidinyl, alkylpyrrolidinyl, halopyrrolidinyl, oxopyrrolidinyl, haloazetidinyl, hydroxyazetidinyl, 1,1-dioxido-2-isothioazolidinyl, tetrahydrofuranyl, cycloalkylamino, hydroxyoxetanyl, alkylsulfonyl, oxetanyl, 6oxa-1-aza-spiro[3.3]heptyl, 3,3-difluoro-2-oxo-azetidinyl, oxo-azetidinyl and oxo-pyrrolidinyl; 
         one of R 3  and R 4  is hydrogen and the other one is —(CR 5 R 6 ) m (CR 7 R 8 )—R 9 ; 
         or R 3  and R 4  together with the nitrogen atom to which they are attached form piperidinyl, 1,1-dioxidotetrahydro-2H-thiopyranyl, thiomorpholinyl, 2-oxa-6-aza-spiro[3.3]heptyl or 1-hydroxyalkylpyrrolidinyl; 
         R 5  and R 6  are each independently selected from the group consisting of: hydrogen, alkyl, haloalkyl, cycloalkyl, cycloalkylalkyl, phenyl, pyridazinyl, halophenyl, pyrimidinyl, alkylsulfanylalkyl and alkylsulfonylalkyl; 
         R 7  and R 8  are each independently selected from the group consisting of: hydrogen, alkyl and cycloalkyl; 
         R 9  is selected from the group consisting of: alkyl, hydroxyl, cyano, carboxyl, alkoxycarbonyl, alkyl[1,2,4]oxadiazolyl, oxazolyl, thiazolyl, [1,3,4]oxadiazolyl, cycloalkyl, phenyl, pyridinyl, tetrahydropyranyl, alkyl[1,2,4]thiadiazolyl, [1,2,4]thiadiazolyl, alkylaminocarbonyl, alkyltetrahydropyranyl, alkylisoxazolyl, aminocarbonyl, morpholinyl, dihydro-oxazolyl, [1,2,4]oxadiazolyl, hydroxycycloalkyl, alkoxycarbonylcycloalkyl, alkoxyalkoxy, hydroxyalkylcycloalkyl, alkoxypyridinyl, piperidinyl, hydroxypiperidinyl, hydroxyalkylpiperidinyl, isoxazolyl, azetidine-carbonyl, alkoxyalkylaminocarbonyl, cycloalkyl-alkylaminocarbonyl, haloazetidinylcarbonyl, alkyloxopyrrolidinyl, 1,1-dioxo-tetrahydro-1λ6-thiophenyl, 1,1-dioxo-tetrahydro-1λ6-thiophenylamino, amino[1,2,4]oxadiazolyl, 4-alkyl-5-oxo-4,5-dihydro-[1,2,4]oxadiazolyl, nitro-benzo[1,2,5]oxadiazolyl, alkylsulfonyl, alkyl[1,2,4]thiazolyl, hydroxyalkylaminocarbonyl, oxotetrahydrofuranyl, (cycloalkylalkyl)(alkoxycarbonyl)amino, 2-oxo-[1,3]oxazinanyl, haloalkyl and hydroxypyrrolidinylaminocarbonyl; 
         m is 0 or 1; and 
         n is 0, 1 or 2; 
         and when R 1  is selected from the group consisting of cycloalkyl, haloalkoxy, alkoxyalkoxy, haloalkylphenyl, phenylalkyl, halophenylalkyl, phenylhydroxyalkyl, phenyloxyalkyl, phenylalkoxy, fluorophenyloxy, piperidinylsulfonyl, tetrahydropyranyl, 3-alkoxyazetidinyl, tetrahydropyranylalkyl, tetrahydropyranylalkoxy, tetrahydrothiopyranyl 1,1 dioxide, 1,1-dioxo-[1,2]thianzinan-4-yl, piperidin-2-onyl, tetrahydrofuranylalkoxy, pyridinylalkoxy, alkyloxetanylalkoxy, hydroxyhaloalkyloxy, halophenylhydroxyalkyl, alkylsufonyl, alkylsulfanyl and (halo) (haloakyl)phenyl; 
         R 2  is selected from the group consisting of hydrogen, halogen, alkyl, haloalkyl, hydroxyalkyl, alkoxy, haloalkoxy, alkylamino, haloalkylamino and alkylsufonyl; 
         with the provise that if R 1  is alkylsulfanyl and m and n are each 0 then R 9  cannot be alkyl; 
         and R 3 , R 4 , R 5 , R 6  R 7 , R 8 , R 9 , m and n are as above; 
         or a pharmaceutically acceptable salt or ester thereof. 
       
     
     
         22 . A compound selected from the group consisting of:
 7,7-Dimethyl-5,6,7,8-tetrahydro-quinoline-2-carboxylic acid ((R)-2-cyclopropyl-2-hydroxypropyl)-amide;   5-(3,3-Difluoro-azetidin-1-yl)-6-(2-methoxy-ethoxy)-pyridine-2-carboxylic acid ((S)-1-carbamoyl-3-methyl-butyl)-amide;   5-(3,3-Difluoroazetidin-1-yl)-N-((S)-3,3-dimethyl-1-(methylamino)-1-oxobutan-2-yl)-6-((tetrahydrofuran-2-yl)methoxy)picolinamide;   5-(3,3-Difluoro-azetidin-1-yl)-6-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide; and   5-(3,3-Difluoro-azetidin-1-yl)-6-(3-methyl-oxetan-3-ylmethoxy)-pyridine-2-carboxylic acid (1-methyl-1-thiazol-2-yl-ethyl)-amide.