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1. WO2015019365 - N-CYANOMÉTHYLAMIDES COMME INHIBITEURS DE LA JANUS KINASE

Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

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We claim:

1. Compound having the structure of general formula (I)


or pharmaceutically acceptable salts thereof

Wherein

X at each occurrence is independently selected from N or CH;

Z at each occurrence is independently selected from N or CH;

n is selected from 0, 1.

A is independently selected from hydrogen, halogen, C1-4 alkyl, CF3, CN, CON(R1)2, O C1-4alkyl

Ring B is selected from following ring systems, each of which can be substituted

The compounds according to claim 1 wherein substituents on the ring B wherever applicable is independently selected from H, OH, CN, NH2, halogen, oxo, OCF3, CF3, C1-C6 alkyl, OC1-C6 alkyl, (CH2)1-6OC1-C6 alkyl, O-(CH2)0-4OC1-C6 alkyl, C(O)NHC1-C6 alkyl, NHC(O)C1-C6 alkyl, S(O)0.2C1-C6 alkyl, (CH2)1-6N(R1)2, (CH2)1.6NHC(=O)OR1, (CH2)1-6NHC(=O)R1, C(=O)OR1, C(=O)R1, (CH2)1-4C(=O) NHR1, (CH2)0-4O(CH2)0-4Ar1, (CH2)0- 4NH(CH2)0-4Ar,, (CH2)0-4 An, (CH2)0-4C(O)(CH2)0-4Ar1, (CH2)0-4 C(=O) O(CH2)0-4Ar1, (CH2)0-4C(=O)NR1(CH2)0-4Ar1.

The compound according to claim 1 and 2 wherein R1 at each occurrence is independently selected from hydrogen, C1-C4 alkyl, C1 -C4 haloalkyl, C3-C7 cycloalkyl groups.

4. The compound according to claim 2 wherein Ar1 at each iteration is independently selected from unsubstituted or substituted aryl or heterocyclic ring substituted with one, two, three or four substituents.

5. The compounds according to claim 4 wherein substituents on Ar1 are independently selected from the group comprising of OH, CN, NH2, halogen,

OCF3, CF3, C1-C6 alkyl, OC1-C6alkyl, (CH2)1-6OC1-C6 alkyl, O-(CH2)0-4OC1- C6 alkyl, C(O)NHC1-C6 alkyl, NHC(O)C1-C6 alkyl, S(O)0-2C1-C6 alkyl, (CH2)1- 6N(R1)2, (CH2)1-6NHC(=O)OR1, (CH2)1-6NHC(=O)R1, C(=O)OR1 or - C(=O)R1, CH2(CH2)0-4C(=O) NHR1.

6. The compound as claimed in claim 1 selected from the group consisting of:

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxopyrrolidin-1-yl)piperidin-1- yl)phenyl)amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(1,1-dioxidoisothiazolidin-2-yl) piperidin-1-yl) phenyl)amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-morpholinopiperidin-1-yl)phenyl)

amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1H-1,2,4-Triazol-1-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4- yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(1H-Pyrazol-1-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)- N-(cyanomethyl)benzamide;

4-(2-((4-([1 ,3'-Bipyrrolidin]- 1-'yl)phenyl)amino)pyrimidin-4-yl)-N- (cyanomethyl) benzamide;

N-(cyanomethyl)-4-(2-((4-(4-(1,1-dioxidotetrahydro-2H-thiopyran-4- yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(furan-2-yl)piperidin-1-yl)phenyl)

amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(1,1-dioxidotetrahydrothiophen-3-yl)piperazin- 1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2,5-dioxopyrrolidin-1-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(thiophen-2-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxooxazolidin-3-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydrofuran-2-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methylfuran-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyltetrahydrofuran-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxoimidazolidin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(l ,3,4-Oxadiazol-2-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4 yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(2H-1,2,3-Triazol-2-yl)piperidin-1-yl)phenyl)amino) pyrimidin-4 yl)-N-(cyano methyl) benzamide;

4-(2-((4-(4-(1H-1 ,2,3-Triazol-1-yl)piperidin-1-yl)phenyl)amino) pyrimidin-4 yl)-N-(cyano methyl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-1H-1,2,4-triazol-4(5H)-yl) piperidin-1-yl) phenyl) amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-1-yl) phenyl) amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxo-1-oxa-8-azaspiro[4.5]decan-8-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(4-cyclopropyl-5-methyl-4H-1,2,4-triazol-3-yl) piperidin-1-yl) phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methoxy-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1,4-Dioxepan-6-yl)piperazin-1-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl) benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-1H-imidazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-1H-imidazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl)pyrrolidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(3,4-dihydroxypyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(6-Acetyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-morpholinopiperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(2-oxopyrrolidin-1 -yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-1-yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-morpholinopiperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(5-Chloro-2-((4-(4-morpholinopiperidin-1-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(2-oxopyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(5-Chioro-2-((4-(4-(2-oxopyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)phenyl)amino)-5-fluoropyrimidin-4-yl)-N-(cyanomethyl)benzamide;

-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)phenyl)amino)-5-chloropyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyn:ol-6(3H)-yl)pipendin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(5-Chloro-2-((4-(4-(tetrahydro-2H-[1,4]dioxino[2,3.-c]pyrrol-6(3H)-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(5-Chloro-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(5-Chloro-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-1-yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-1-yl)phenyl)amino)-5-fluoropyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-1-yl)phenyl)amino)-5-chloropyrimidin-4-yl)-N-(cyanomethyl)benzamide;

7. The compound as claimed in any preceding claim preferably selected from the group consisting of:

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxopyrrolidin-1-yl)piperidin-1-yl)phenyl)amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(1, l -dioxidoisothiazolidin-2-yl) piperidin-1-yl) phenyl)amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-morpholinopiperidin-1-yl)phenyl)

amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1H-1,2,4-Triazol-1-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(1H-Pyrazol-1-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-([1,3'-Bipyrrolidin]- 1'-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl) benzamide;

N-(cyanomethyl)-4-(2-((4-(4-(1,1 -dioxidotetrahydro-2H-thiopyran-4-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(furan-2-yl)piperidin-1-yl)phenyl)

amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(l ,1-dioxidotetrahydrothiophen-3-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2,5-dioxopyrrolidin-1-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(thiophen-2-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxooxazolidin-3-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydrofuran-2-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methylfuran-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyltetrahydrofuran-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxoimidazolidin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(l ,3,4-Oxadiazol-2-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(2H-1,2,3-Triazol-2-yl)piperidin-1-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyano methyl) benzamide;

4-(2-((4-(4-(1H-1,2,3-Triazol-1-yl)piperidin-1-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyano methyl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-1H-1,2,4-triazol-4(5H)-yl) piperidin-1-yl) phenyl) amino) pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-1-yl) phenyl) amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-1,3,4-thiadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(2-oxo-1-oxa-8-azaspiro[4.5]decan-8-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(4-cyclopropyl-5-methyl-4H-1,2,4-triazol-3-yl) piperidin-1-yl) phenyl) amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methoxy-1,3,4-oxadiazol-2-yl)piperidin-1-yl)phenyl) amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1,4-Dioxepan-6-yl)piperazin-1-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl) benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-1H-imidazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-1H-imidazol-2-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(3-(tetrahydro-2H-[1,4]dioxino[2,3-c]pyrrol-6(3H)-yl)pyrrolidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-1,3,4-oxadiazol-2-yl)piperazin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(2-((4-(4-(3,4-dihydroxypyrrolidin-1-yl)piperidin-1-yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)piperidin-1-yl)phenyl) amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

4-(2-((4-(4-(6-Acetyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)piperidin-ί- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-morpholinopiperidin-1- yl)phenyl)amino)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(2-oxopyrrolidin-1-yl)piperidin-1- yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(2-((4-(4-(1-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-1-yl)phenyl)amino)-5- methylpyrimidin-4-yl)-N-(cyanomethyl)benzamide;

N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(5-methyl-1,3,4-oxadiazol-2- yl)piperidin-1-yl)phenyl)amin0)pyrimidin-4-yl)benzamide;

N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-morpholinopiperidin-1- yl)phenyl)amino)pyrimidin-4-yl)benzamide;

4-(5-Chloro-2-((4-(4-morpholinopiperidin-1-yl)phenyl)amino) pyrimidin-4- yl)-N-(cyanomethyl)benzamide;

8. A pharmaceutical composition comprising a therapeutically effective amount of a compound of Formula (I) as claimed in any of the preceding claims and optionally one or more pharmaceutically acceptable carriers, diluents or excipients.

9. The compounds as claimed in any preceding claims suitable as JAK inhibitors.

10. A method of treating diseases medicated by the JAK protein which comprising administering to a patient in need thereof an effective amount of a compound of Formula (I) as claimed in any of the preceding claims or its suitable pharmaceutical composition.

11. The use of compounds of formula (1) or its pharmaceutical compositions as claimed in any of the preceding claim suitable for treatment of diseases wherein the JAK kinase has a pathophysiological function.

12. The pharmaceutical composition comprising compounds of formula 1 along with suitable excipients suitable for the treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy and transplant rejection, diseases involving impairment of cartilage turnover, congenital cartilage malformations, and/or diseases associated with hypersecretion of IL6 or interferons.

13. An intermediate of formula 4 and their isomers.