DK3030561T3 - N-cyanomethylamider som inhibitorer af janus kinase - Google Patents

N-cyanomethylamider som inhibitorer af janus kinase Download PDF

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DK3030561T3
DK3030561T3 DK14793899.7T DK14793899T DK3030561T3 DK 3030561 T3 DK3030561 T3 DK 3030561T3 DK 14793899 T DK14793899 T DK 14793899T DK 3030561 T3 DK3030561 T3 DK 3030561T3
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phenyl
amino
cyanomethyl
benzamide
pyrimidin
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Ranjit C Desai
Jigar Desai
Pankaj Patel
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Cadila Healthcare Ltd
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Claims (11)

1. Forbindelse med strukturen af generel formel (I)
eller farmaceutisk acceptable salte deraf hvor X ved hver forekomst er uafhængigt valgt fra N eller CH; Z ved hver forekomst er uafhængigt valgt fra N eller CH; n er valgt fra 0,1. A er uafhængigt valgt fra hydrogen, halogen, Ci-4 alkyl, CF3, CN, CON(Ri)2, OC1-4 alkyl Ring B er valgt fra følgende ringsystemer, hver af hvilke kan blive substitueret
2. Forbindelserne ifølge krav 1, hvor substituenter på ring B, hvor det er relevant, er uafhængigt valgt fra H, OH, CN, NH2, halogen, oxo, OCF3, CF3, C1-C6 alkyl, OC1-C6 alkyl, (CHzh-eOCi-Ce alkyl, 0-(CH2)o-40Ci-C6 alkyl, C(0)NHCi-Ce alkyl, NHC(0)Ci-Ce alkyl, S(0)o-2Ci-Ce alkyl, (CH2)i-6N(Ri)2, (CH2)i-6NHC(=0)0Ri, (CH2)i-6NHC(=0)Ri, C(=0)0Ri, C(=0)Ri, (CH2)i-4C(=0) NHRi, (CH2)o-40(CH2)o-4An, (CH2)o-4NH(CH2)o-4Ari, (CH2)o-4 An, (CH2)o-4C(0)(CH2)o-4Ari, (CH2)o-4 C(=0) 0(CH2)o-4An, (CH2)o-4C(=0)NRi(CH2)o-4An.
3. Forbindelsen ifølge krav 1 og 2, hvor Ri ved hver forekomst er uafhængigt valgt fra hydrogen, Ci-C4 alkyl, C1-C4 haloalkyl, C3-C7 cykloalkylgrupper.
4. Forbindelsen ifølge krav 2, hvor An ved hver gentagelse er uafhængigt valgt fra usubstitueret eller substitueret aryl eller heterocyklisk ring substitueret med en, to, tre eller fire substituenter.
5. Forbindelserne ifølge krav 4, hvor substituenter på An er uafhængigt valgt fra gruppen omfattende OH, CN, NH2, halogen, OCF3, CF3, C1-C6 alkyl, OCi-C6alkyl, (CH2)i-60Ci-C6 alkyl, 0-(CH2)o-4OCi-C6 alkyl, C(0)NHCi-C6 alkyl, NHC(0)Ci-Ce alkyl, S(0)o-2Ci-C6 alkyl, (CH2)i-6N(Ri)2, (CH2)i-6NHC(=0)0Ri, (CH2)i-6NHC(=0)Ri, C(=0)0Ri eller -C(=0)Ri, CH2(CH2)o-4C(=0)NHRi.
6. Forbindelsen ifølge krav 1, valgt fra gruppen bestående af: N-(Cyanomethyl)-4-(2-((4-(4-(2-oxopyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(l,l-dioxidoisothiazolidin-2-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-morpholinopiperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( IH-1,2,4-Triazol-l-yl) piperid in-l-yl)phenyl)amino)pynm id in-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-( 1 H-Pyrazol-l-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-([l,3'-Bipyrrolidin]-l'-yl)phenyl)amino)pynmidin-4-yl)-N-(cyanomethyl) benzamid; N-(cyanomethyl)-4-(2-((4-(4-(l,l-dioxidotetrahydro-2H-thiopyran-4- yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(furan-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(l,l-dioxidotetrahydrothiophen-3- yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2,5-dioxopyrrolidin-l-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(thiophen-2-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2-oxooxazolidin-3-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzannid; N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydrofuran-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methylfuran-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyltetrahydrofuran-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2-oxoimidazolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-(1,3,4-Oxadiazol-2-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(2H-l,2,3-Triazol-2-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyano methyl) benzamid; 4-(2-((4-(4-( 1H-1,2,3-Triazol-l-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyano methyl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-lH-l,2,4-triazol-4(SH)-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-lH-l,2,4-triazol-l- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( l-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-l,3,4-oxadiazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-l,3,4-thiadiazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-[l,4]dioxino[2,3-c]pyrrol- 6(3H)-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2-oxo-l-oxa-8-azaspiro[4.5]decan-8- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-l,3,4-oxadiazol-2- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(4-cyclopropyl-5-methyl-4H-l,2,4-triazol-3-yl)piperidin-l-yl) phenyl) amino)pyrimidin-4-yl)benzannid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methoxy-l,3,4-oxadiazol-2-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( 1,4-Dioxepan-6-yl)pipe razin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl) benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-lH-imidazol-2-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-lH-imidazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(3-(tetrahydro-2H-[l,4]dioxino[2,3-c]pyrrol- 6(3H)-yl)pyrrolidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-l,3,4-oxadiazol-2-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(3,4-dihydroxypyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzannid; 4-(2-((4-(4-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl)benzannid; 4-(2-((4-(4-(6-Acetyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-morpholinopiperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(2-oxopyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( l-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-l-yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-morpholinopiperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(5-Chloro-2-((4-(4-morpholinopiperidin-l-yl)phenyl)amino)pyrimidin-4- yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(2-oxopyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(5-Chloro-2-((4-(4-(2-oxopyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)-5-fluoropyrimidin-4-yl)-N-(cyanomethyl)benzamid; -(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)-5-chloropyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(tetrahydro-2H-[l,4]dioxino(2,3- c]pyrrol-6(3H)-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(tetrahydro-2H-[l,4]dioxino[2,3- c]pyrrol-6(3H)-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(5-Chloro-2-((4-(4-(tetrahydro-2H-[l,4]dioxino[2,3-c]pyrrol-6(3H)- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-l\l-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(5-Chloro-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2- yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2- yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(5-Chloro-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-l- yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-l- yl)phenyl)amino)-5-fluoropyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(3-Thia-6-azabicyclo[3.1.1]heptan-6-yl)piperidin-l- yl)phenyl)amino)-5-chloropyrimidin-4-yl)-N-(cyanomethyl)benzamid;
7. Forbindelsen ifølge et hvilket som helst af de foregående krav valgt fra gruppen bestående af: N-(Cyanomethyl)-4-(2-((4-(4-(2-oxopyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(l,l-dioxidoisothiazolidin-2-yl)piperidin-l-yl) phenyl)amino) pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-morpholinopiperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( 1H-1,2,4-Triazol-l-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-(4-((4-( lH-Pyrazol-l-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-([l,3,-Bipyrrolidin]-l'-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl) benzamid; N-(cyanomethyl)-4-(2-((4-(4-(l,l-dioxidotetrahydro-2H-thiopyran-4- yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(furan-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(l,l-dioxidotetrahydrothiophen-3- yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2,5-dioxopyrrolidin-l-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(thiophen-2-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2-oxooxazolidin-3-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydrofuran-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methylfuran-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-pyran-4-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyltetrahydrofuran-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-(6-Oxa-3-azabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2-oxoimidazolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-(1,3,4-Oxadiazol-2-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(2H-l,2,3-Triazol-2-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyano methyl) benzamid; 4-(2-((4-(4-(lH-l,2,3-Triazol-l-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyano methyl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-lH-l,2,4-triazol-4(SH)-yl)piperidin-l-yl)phenyl) amino) pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-lH-l,2,4-triazol-l- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( l-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-l,3,4-oxadiazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-l,3,4-thiadiazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(tetrahydro-2H-[l,4]dioxino[2,3-c]pyrrol- 6(3H)-yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(2-oxo-l-oxa-8-azaspiro[4.5]decan-8- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-oxo-4,5-dihydro-l,3,4-oxadiazol-2- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(4-cyclopropyl-5-methyl-4H-l,2,4-triazol-3-yl)piperidin-l-yl) phenyl) amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methoxy-l,3,4-oxadiazol-2-yl)piperidin-l-yl)phenyl) amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( l,4-Dioxepan-6-yl)piperazin-l-yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl) benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-lH-imidazol-2-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(4,5-dihydro-lH-imidazol-2-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(3-(tetrahydro-2H-[l,4]dioxino[2,3-c]pyrrol- 6(3H)-yl)pyrrolidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(5-methyl-l,3,4-oxadiazol-2-yl)piperazin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(2-((4-(4-(3,4-dihydroxypyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-(8-Oxa-3-azabicyclo[3.2.1]octan-3-yl)piperidin-l-yl)phenyl)amino) pyrimidin-4-yl)-N-(cyanomethyl)benzamid; 4-(2-((4-(4-(6-Acetyl-3,6-diazabicyclo[3.1.1]heptan-3-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-morpholinopiperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(2-oxopyrrolidin-l-yl)piperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(2-((4-(4-( l-Oxa-8-azaspiro[4.5]decan-8-yl)piperidin-l-yl)phenyl)amino)-5-methylpyrimidin-4-yl)-N-(cyanomethyl)benzamid; N-(Cyanomethyl)-4-(5-methyl-2-((4-(4-(5-methyl-l,3,4-oxadiazol-2- yl)piperidin-l-yl)phenyl)amino)pyrimidin-4-yl)benzamid; N-(Cyanomethyl)-4-(5-fluoro-2-((4-(4-morpholinopiperidin-l- yl)phenyl)amino)pyrimidin-4-yl)benzamid; 4-(5-Chloro-2-((4-(4-morpholinopiperidin-l-yl)phenyl)amino)pyrimidin-4- yl)-N-(cyanomethyl)benzamid;
8. Farmaceutisk sammensætning omfattende en terapeutisk effektiv mængde af en forbindelse af formel (I) ifølge et hvilket som helst af de foregående krav og eventuelt en eller flere farmaceutisk acceptable bærere, diluenter eller excipienser.
9. Forbindelserne ifølge et hvilket som helst af de foregående krav til anvendelse i behandlingen af inflammatoriske tilstande, autoimmune sygdomme, proliferative sygdomme, allergi og transplantatafstødning, sygdomme involverende forringelse af brusk omsætning, medfødte brusk deformiteter, og/eller sygdomme forbundet med hypersekretion af IL6 eller interferoner, hvor JAK kinasen har en patofysiologisk funktion.
10. Den farmaceutiske sammensætning omfattende forbindelser af formel 1 ifølge krav 1 sammen med egnede excipienser egnet til behandlingen af inflammatoriske tilstande, autoimmune sygdomme, proliferative sygdomme, allergi og transplantatafstødning, sygdomme involverende forringelse af brusk omsætning, medfødte brusk deformiteter, og/eller sygdomme forbundet med hypersekretion af IL6 eller interferoner.
11. Intermediat af formel 4
hvor B, Z, X, n og A er defineret som i krav 1.
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AR097282A1 (es) 2016-03-02
KR101665301B1 (ko) 2016-10-11
HRP20170277T1 (hr) 2017-05-19
EP3030561B1 (en) 2017-01-11
JP2016525071A (ja) 2016-08-22
HUE033448T2 (en) 2017-11-28

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