DK2788349T3 - Kinasehæmmere - Google Patents

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DK2788349T3
DK2788349T3 DK12809140.2T DK12809140T DK2788349T3 DK 2788349 T3 DK2788349 T3 DK 2788349T3 DK 12809140 T DK12809140 T DK 12809140T DK 2788349 T3 DK2788349 T3 DK 2788349T3
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tert
yloxy
butyl
tetrahydro
urea
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Niel Monique Bodil Van
Nicholas Charles Ray
Lilian Alcaraz
Terry Aaron Panchal
Andrew Stephen Robert Jennings
Elisabetta Armani
Andrew Peter Cridland
Christopher Hurley
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Chiesi Farm Spa
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Claims (12)

1. Forbindelse med formel (I) eller et farmaceutisk acceptabelt salt deraf:
hvor; WerNH; Y er O; R1 er en gruppe udvalgt blandt (Ila) - (Ile):
R8 og R9 hver især uafhængigt er hydrogen eller CrC6-alkyl, eller R8 og R9 sammen med det nitrogenatom, som de er bundet til, kan danne et 5-11-leddet mættet monocyklisk eller et kondenseret eller spiro bicyklisk ringsystem eventuelt indeholdende et yderligere heteroatom, som er oxygen eller nitrogen, hvor nitrogenatomet eventuelt er substitueret med CrC6-alkyl; hvor sådanne CrC6-alkylgrupper kan være eventuelt substitueret med en gruppe C-i-Ce-alkyl, C3-Cs-cycloalkyl, hydroxyl eller halo; X1, X2, X3, X4 og X5 hver især uafhængigt er et carbonatom, et nitrogenatom, en -(CH)-gruppe eller en -NH-gruppe; således at hver kombination deraf danner et aromatisk ringsystem; R10 er udvalgt fra en gruppe bestående af: Hydrogen, -CN, -NRARB, -N(Rc)(C2-C6alkylen)-NRARB, -N(Rc)(C3-C7cycloalkylen)-NRARB, -(CrC6alky-len)-NRARB, -(C3-C7cycloalkylen)-NRARB, -0-(C2-C6alkylen)-NRARB, -0-(C3-C7cycloalkylen)-NRARB, -S-(C2-C6alkylen)-NRARB, -S-(C3-C7cycloalkylen)-NRaRb, -N(Rc)C(0)-(CrC6alkylen)-NRARB, -N(RG)C(0)-(C3-C7cycloalkylen)-NRaRb, -C(0)N(Rc)-(C2-C6alkylen)-NRARB, -C(0)N(RC)-(C3-C7cycloalkylen)-NRaRb, -C(0)N(Rc)-(C2-C6alkylen)-0RD, -C(0)N(Rc)-(C3-C7cycloalkylen)- 0Rd, -N(Rc)C(0)NRaRb, -C(0)NRaRb, -N(Rc)C(0)N(Rc)-(C2-C6alkylen)-NRaRb, -N(Rc)C(0)N(Rc)-(C3-C7cycloalkylen)-NRARB, -(C2-C6alkylen)-ORD, -(C3-C7cycloalkylen)-ORD, -0-(C2-C6alkylen)-0RD, -0-(C3-C7cycloalkylen)-0Rd, -S-(C2-C6alkylen)-ORD, -S-(C3-C7cycloalkylen)-ORD, -N(Rc)S(0)2-(Cr C6alkylen)-NRARB, -N(Rc)S(0)2-(C3-C7cycloalkylen)-NRARB, -S(0)2N(Rc)-(C2-C6alkylen)-NRARB, -S(0)2N(Rc)-(C3-C7cycloalkylen)-NRARB, -S(0)2N(Rc)-(C2-C6alkylen)-ORD, -S(0)2N(Rc)-(C3-C7cycloalkylen)-ORD, -N(Rc)S(0)2-(C2-C6alkylen)-ORD, -N(Rc)S(0)2-(C3-C7cycloalkylen)-ORD,-S(0)2N(RARB), -N(Rc)S(0)2Rd, -N(Rc)C(0)Rc, -0Rc, -SRc, -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(CrC6alkyl), (C5-C7heterocycloalkyl)(C3-C6cycloalkyl)-, og C3-C7heterocycloalkylcarbonyl; hvor en hvilken som helst af en sådan Cr C6alkyl, C3-C6cycloalkyl, -(CrC6alkylen)-, -(C2-C6alkylen)-, -(C3-C7cycloalky-len)-, -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(CrC6alkyl), (C5-C7. heterocycloalkyl)-(C3-C6cycloalkyl) og (C3-C7heterocycloalkyl)carbonyl-del i de ovenfor angivne grupper kan være eventuelt substitueret med en gruppe C-|-C6-alkyl, C3-C7-cycloalkyl, hydroxyl eller halo; R11 er bundet til X4 og er udvalgt fra en gruppe bestående af: Hydrogen; -CN; C-|-Cs-alkyl, som er substitueret med en gruppe udvalgt blandt -CN, -ORc, -SRC, halo; C3-C6cycloalkyl, som er substitueret med en gruppe udvalgt blandt CrC4-alkyl, -CN, -ORc, -SR°, halo; -NRARB, -N(Rc)(C2-C6alkylen)-NRARB, -N(RG)(C3-C7cycloalkylen)-NRARB, -(CrC6alky-len)-NRARB, -(C3-C7cycloalkylen)-NRARB, -0-(C2-C6alkylen)-NRARB, -0-(C3-C7cycloalkylen)-NRARB, -S-(C2-C6alkylen)-NRARB, -S-(C3-C7cycloalkylen)-NRARB, -N(Rc)C(0)-(CrC6alkylen)-NRARB, -N(Rc)C(0)-(C3-C7cycloalkylen)-NRaRb, -C(0)N(RG)-(C2-C6alkylen)-NRARB, -C(0)N(RG)-(C3-C7cycloalkylen)-NRaRb, -C(0)N(Rc)-(C2-C6alkylen)-0RD, -C(0)N(RG)-(C3-C7cycloalkylen)-ORd, -N(Rc)C(0)N(RaRb), -C(0)N(RaRb), -N(Rc)C(0)N(Rc)-(C2-C6alkylen)-NRaRb, -N(Rc)C(0)N(Rc)-(C3-C7cycloalkylen)-NRARB, -0-(C2-C6alkylen)-ORd, -0-(C3-C7cycloalkylen)-ORD, -S-(C2-C6alkylen)-ORD, -S-(C3-C7cyclo-alkylen)-OR°, -N(Rc)S(0)2-(CrC6alkylen)-NRARB, -N(Rc)S(0)2-(C3-C7cyclo-alkylen)-NRARB, -S(0)2N(Rc)-(C2-C6alkylen)-NRARB, -S(0)2N(Rc)-(C3-C7cy-cloalkylen)-NRARB, -S(0)2N(Rc)-(C2-C6alkylen)-0RD, -S(0)2N(Rc)-(C3-C7cy-cloalkylen)-ORD, -N(Rc)S(0)2-(C2-C6alkylen)-0RD, -N(Rc)S(0)2(C3-C7cyclo-alkylen)-OR°, -S(0)2N(RARB), -N(Rc)S(0)2RD, -N(Rc)C(0)Rc, ORc, SRC, -(C3-C7heterc>cycloalkyl), (C5-C7heterocycloalkyl)-(Ci-C6alkyl), (C5-C7hetero-cycloalkyl)(C3-C6cycloalkyl) og (C3-C7heterocycloalkyl)carbonyl, hvor en hvilken som helst af en sådan CrC6alkyl, C3-C6cycloalkyl, -(CrCealkylen)-, -(C2-C6alkylen)-, -(C3-C7cycloalkylen)-, -(C3-C7heterocycloalkyl), (C5-C7hete-rocycloalkyl)-(CrC6alkyl), (C5-C7heterocycloalkyl)-(C3-C6cycloalkyl) og (C3-C7heterocycloalkyl)carbonyl-del i de ovenfor angivne grupper kan være eventuelt substitueret med en, to eller tre R25-grupper, som er uafhængigt udvalgt i listen bestående af: CrC6-alkyl, (CrC3)-haloalkyl, (CrC4)hydroxyalkyl, C3-C7-cycloalkyl, hydroxyl og halo; eller R11 er bundet til X4 og er phenyl eller 5- eller 6-leddet monocyklisk heteroaryl, hvor en sådan phenyl eller 5- eller 6-leddet monocyklisk heteroaryl er substitueret med en gruppe udvalgt i listen bestående af: CrC6-alkyl, som er substitueret med en -CN-gruppe; C3-C6-cycloalkyl, som er substitueret med en gruppe udvalgt blandt: -CN, -ORc, -SRC eller halo; -N(Rc)(C2-C6alkylen)-NRaRb, -N(Rc)(C3-C7cycloalkylen)-NRARB, -(CrC6alkylen)-NRARB, -(C3-C7cy-cloalkylen)-NRARB, -0-(C3-C7cycloalkyien)-NRARB, -S-(C2-C6alkylen)-NRARB, -S-(C3-C7cycloalkylen)-NRARB, -N(Rc)C(0)-(CrC6alkylen)-NRARB, -N(Rc)C(0)-(C3-C7cycloaikylen)-NRARB, -C(0)N(Rc)-(C2-C6alkylen)-NRARB, -C(0)N(Rc)-(C3-C7cycloaikylen)-NRARB, -C(0)N(Rc)-(C2-C6alkylen)-0RD, -C(0)N(Rc)-(C3-C7cycloalkylen)-ORD, -N(Rc)C(0)N(Rc)-(C2-C6alkylen)-NRaRb, -N(Rc)C(0)N(Rc)-(C3-C7cycloalkylen)-NRARB, -0-(C3-C7cycloalky-len)-OR°, -S-(C3-C7cycloalkylen)-ORD,-N(Rc)S(0)2-(CrC6alkylen)-NRARB, -N(Rc)S(0)2-(C3-C7cycloalkylen)-NRARB, -S(0)2N(Rc)-(C2-C6alkylen)-NRARB, -S(0)2N(Rc)-(C3-C7cycloalkylen)-NRARB,-S(0)2N(Rc)-(C2-C6alkylen)-0RD, -S(0)2N(RC)-(C3-C7cycloalkylen)-ORD, -N(Rc)S(0)2-(C2-C6alkylen)-0RD, -N(Rc)S(0)2-(C3-C7cycloalkylen)-ORD, -N(Rc)S(0)2RD, -(C3-C7heterocyclo-alkyl), (C5-C7heterocycloalkyl)-(Ci-C6alkyl), (C5-C7heterocycloalkyl)(C3-C6cy-cloalkyl) og (C3-C7heterocycloalkyl)carbonyl, hvor en hvilken som helst af en sådan CrC6alkyl, C3-C6cycloalkyl, -(CrC6alkylen)-, -(C2-C6alkylen)-, -(C3-C7cycloalkylen)-, -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(Cr Ce-alkyl), (C5-07-heterocycloalkyl)-(C3-C6-cycloalkyl) og (C3-C7heterocyclo-alkyl)carbonyl-del i de ovenfor angivne grupper kan være eventuelt substitueret med en, to eller tre R25-grupper, som er uafhængigt udvalgt fra gruppen bestående af: CrC6-alkyl, (CrC3)-haloalkyl, (CrC4)hydroxyalkyl, C3-C7cyclo-alkyl, hydroxyl og halo; Ra og Rb ved hver forekomst uafhængigt er hydrogen, CrC6-alkyl eller C3-C7-cycloalkyl, hvor en sådan CrC6-alkyl og C3-C7-cycloalkyl eventuelt er substitueret med en gruppe CrC3-alkyl, C3-C7cycloalkyl, -ORD, -CN eller halo; alternativt, RA og RB, sammen med det nitrogenatom, som de er bundet til, kan danne et 5-11-leddet mættet heterocyklisk monocyklisk eller bicyklisk ringsystem, som eventuelt er substitueret med en eller flere grupper -OR°, -CN, halo, CrC6-alkyl eller C3-C7-cycloalkyl, hvor en sådan CrC6-alkyl og C3-C7-cycloalkyl eventuelt er substitueret med en gruppe Ci-C3-alkyl, C3-C7cycloalkyl, -OR°, -CN eller halo; og hvilken 5-11-leddet mættet heterocyklisk monocyklisk eller bicyklisk ring eventuelt indeholder et yderligere hetero-atom, som er oxygen eller nitrogen, hvor nitrogenatomet eventuelt er substitueret med CrC6-alkyl eller C3-C6-cycloalkyl, hvor en hvilken som helst af en sådan Ci-C6-alkyl eller C3-C6-cycloalkyl kan være eventuelt substitueret med en gruppe CrC6-alkyl, C3-C7-cycloalkyl, -OR°, -CN eller halo; og/eller RA og Rb kan være bundet til et carbonatom af -(CrC6alkylen)-, -(C2-C6alkylen)-eller -(C3-C7cycloalkylen)-delen af gruppen bundet til det nitrogen, som de er forbundet med, for at danne en mættet cyklus på op til 6 ringatomer; Rc ved hver forekomst uafhængigt er hydrogen, CrC6-alkyl eller C3-C6-cycloalkyl, hvor en sådan CrC6-alkyl og C3-C6-cycloalkyl eventuelt er substitueret med en gruppe C-i-C3-alkyl, -OR°, -CN eller halo; Rd ved hver forekomst uafhængigt er hydrogen, -CH3 eller -C2H5; R12 og R13 uafhængigt er hydrogen, CrC6-alkyl eller halogen; A er et divalent cycloalkylen-radikal med 5 eller 6 ringatomer; hvor cycloalky-lenringen er bundet til W og Y, og kondenseret til en phenylring, hvor en sådan phenylring er eventuelt substitueret med en eller to R24-grupper; og hvor det divalente cycloalkylen-radikal har formlen
R24 ved hver forekomst uafhængigt er udvalgt fra gruppen bestående af: Cr C6-alkyl, halogen og cyano; R2 er et radikal med formel (Illa), (IMb), (IIle) eller (llld):
hvor R14 er udvalgt fra gruppen bestående af: -F, -CH3, -C2H5, -CH2OH, -CH2OMe, -CF2CF3, -CH2SCH3j -SCH3 og -SC2H5; R15 og R16 uafhængigt er -CFI3 eller -C2Fl5; R17 er udvalgt fra gruppen bestående af: ionelektronpar, hydrogen, -CF3, -NReRf, -(C3-C7cycloalkyl), -(C3-C7heterocycloalkyl), aryl eller heteroaryl, hvor en hvilken som helst af en sådan -(C3-C7cycloalkyl), -(C3-C7heterocy-cloalkyl), aryl eller heteroaryl kan være eventuelt substitueret med en gruppe CrC6-alkyl, C3-C7-cycloalkyl eller halo; eller R17 er en
pruppe med den almene formel (IV) hvor R20 er udvalgt fra gruppen bestående af: -F, -CH3, -C2H5, -CFI2OH, -CH2OMe, -CF2CF3, -CH2SCH3, -SCH3 og -SC2H5; R21 er -CH3 eller -C2H5; eller R20 og R21 som defineret ovenfor sammen med det carbonatom, som de er bundet til, kan danne en mættet 3-7-leddet monocyklisk ring; Re og Rf hver især uafhængigt er CrC6-alkyl, eventuelt substitueret med en gruppe CrC3alkyl, -OR°, -CN eller halo; alternativt, RE og RF sammen med det nitrogenatom, som de er bundet til, kan danne et 5-11-leddet mættet monocyklisk eller bicyklisk heterocyklisk ringsystem, som eventuelt er substitueret med en eller flere grupper -ORG, -CN, halo, Ci-C6alkyl eller C3-C7cyclo-alkyl, hvor en sådan CrC6alkyl og C3-C7cycloalkyl eventuelt er substitueret med en gruppe CrC3alkyl, C3-C7cycloalkyl, -ORG, -CN eller halo; og hvilken 5-11-leddet mættet monocyklisk eller bicyklisk heterocyklisk ring eventuelt indeholder et yderligere heteroatom, som er oxygen eller nitrogen, hvor nitrogenatomet eventuelt er substitueret med CrC6alkyl eller C3-C6cycloalkyl, hvor en hvilken som helst af en sådan CrCealkyl eller C3-C6cycloalkyl kan være eventuelt substitueret med en gruppe CrC6alkyl eller C3-C7cycloalkyl; Rg er hydrogen, -CH3 eller -C2H5; R18 er udvalgt fra gruppen bestående af: ionelektronpar, hydrogen, aryl, hete-roaryl, -(CrC6alkyl), -(C3-C7cycloalkyl), -(C3-C7heterocycloalkyl), (C5-C7hete-rocycloalkyl)-(CrC6alkyl) og (C5-C7heterocycloalkyl)-(C3-C6-cycloalkyl), hvor en hvilken som helst af en sådan aryl, heteroaryl, -(CrC6alkyl), -(C3-C7cyclo-alkyl), -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(Ci-C6alkyl) og (C5-C7heterocycloalkyl)-(C3-C6cycloalkyl) kan være eventuelt substitueret med en gruppe -CN, -OH, halo, -COORM, CrCealkyl, C3-C6cycloalkyl, -0-(Cr C6alkyl), -0-(C3-C6cycloalkyl), -S-(Ci-C6alkyl), -S-(C3-C6cycloalkyl), -NRHRJ, -N(RL)(C2-C6alkylen)-NRHRJ, -N(RL)(C3-C7cycloalkylen)-NRHRJ, -(CrC6alky-len)-NRHRJ, -(C3-C7cycloalkylen)-NRHRJ, -0-(C2-C6alkylen)-NRHRJ, -0-(C3-C7cycloalkylen)-NRHRJ, -S-(C2-C6alkylen)-NRHRJ, -S-(C3-C7cycloalkylen)-NRhRj, -N(RL)C(0)-(CrC6alkylen)-NRHRJ, -N(RL)C(0)-(C3-C7cycloalkylen)-NRhRj, -C(0)N(RL)-(C2-C6alkylen)-NRHRJ, -C(0)N(RL)-(C3-C7cycloalkylen)-NRhRj, -C(0)N(RL)-(C2-C6alkylen)-0RM, -C(0)N(RL)-(C3-C7cycloalkylen)-ORm, -N(Rl)C(0)N(RhRj), -C(0)N(RhRj), -N(RL)C(0)N(RL)-(C2-C6alkylen)-NRhRj, -N(RL)C(0)N(RL)-(C3-C7cycloalkylen)-NRHRJ, -0-(C2-C6alkylen)-0RM, -0-(C3-C7cycloalkylen)-ORM, -S-(C2-C6alkylen)-ORM, -S-(C3-C7cycloalkylen)-ORm, -N(Rl) S(0)2-(C1-C6alkylen)-NRHRJ, -N(RL)S(0)2-(C3-C7cycloalkylen)-NRhRj, -S(0)2N(RL)-(C2-C6alkylen)-NRHRJ, -S(0)2N(RL)-(C3-C7cycloalkylen)-NRhRj, -S(0)2N(RL)-(C2-C6alkylen)-0RM, -S(0)2N(RL)-(C3-C7cycloalkylen)-ORm, -N(RL)S(0)2-(C2-C6alkylen)-0RM, -N(RL)S(0)2-(C3-C7cycloalkylen)-ORm, -S(0)2N(RhRj), -N(Rl)S(0)2Rl, -N(Rl)C(0)Rl, ORl, SRl, -(C3-C7hete-rocycloalkyl), (C5-C7heterocycloalkyl)-(CrC6-alkyl) og (C5-C7-heterocyclo-alkyl)-(C3-C6-cycloalkyl), hvor en hvilken som helst af en sådan CrC6alkyl, C3-C6cycloalkyl, -(CrCealkylen)-, -(C2-C6alkylen)-, -(C3-C7cycloalkylen)-, -(C3-C7heterocycloalkyl), (C5-C7heterocycloalkyl)-(CrC6alkyl) og (C5-C7hete-rocycloalkyl)-(C3-C6cycloalkyl)-del i de ovenfor angivne grupper kan være eventuelt substitueret med en gruppe CrC6alkyl, C3-C7cycloalkyl, -ORL eller halo; Rh og RJ, ved hver forekomst uafhængigt er hydrogen, CrCealkyl eller C3-Cecycloalkyl, hvor en sådan CrC6alkyl eller C3-C6cycloalkyl eventuelt er substitueret med en gruppe CrC3alkyl, -ORM, CN eller halo; alternativt, RH og RJ sammen med det nitrogenatom, som de er bundet til, også kan danne et 5-11-leddet mættet monocyklisk eller bicyklisk heterocyk-lisk ringsystem, som eventuelt er substitueret med en eller flere grupper -ORm, -CN, halo, CrC6alkyl eller C3-C7Cycloalkyl, hvor en sådan CrC6alkyl og C3-C7cycloalkyl eventuelt er substitueret med en gruppe CrC3alkyl, C3-C7cycloalkyl, -ORM, CN eller halo; og hvilken 5-11-leddet mættet monocyklisk eller bicyklisk heterocyklisk ring eventuelt indeholder et yderligere hetero-atom, som er oxygen eller nitrogen, hvor nitrogenatomet eventuelt er substitueret med CrC6alkyl eller C3-C6cycloalkyl, hvor en hvilken som helst af en sådan CrC6alkyl eller C3-C6cycloalkyl kan være eventuelt substitueret med en gruppe CrC6alkyl, C3-C7cycloalkyl, -ORM, CN eller halo; og/eller RH og RJ kan være bundet til et carbonatom af -(CrC6alkylen)-, -(C2-C6alkylen)- eller -(C3-C7cycloalkylen)-delen af gruppen bundet til det nitrogen, som de er forbundet med, for at danne en mættet cyklus på op til 6 ringatomer; Rl ved hver forekomst uafhængigt er hydrogen, CrC6alkyl eller C3-C6cyclo-alkyl, hvor en sådan CrC6alkyl eller C3-C6cycloalkyl eventuelt er substitueret med en gruppe CrC3alkyl, -ORM, -CN eller halo; Rm ved hver forekomst uafhængigt er hydrogen, CrC6alkyl eller C3-C6cyclo-alkyl, hvor en sådan CrC6alkyl eller C3-C6cycloalkyl eventuelt er substitueret med en gruppe hydroxyl, -CN eller halo; z1, z2, z3 og z4 uafhængigt er udvalgt fra gruppen bestående af: C, N, S, O, en gruppe -CH- og en gruppe -NH-, i en sådan kombination, at den resulterende dannede ring er et aromatisk system; R19 er udvalgt fra gruppen bestående af: hydrogen, -CF3, -NRERF, -(C3-C7cycloalkyl), -(C3-C7heterocycloalkyl), aryl eller heteroaryl, hvor en hvilken som helst af en sådan -(C3-C7cycloalkyl), -(C3-C7heterocycloalkyl), aryl eller heteroaryl kan være eventuelt substitueret med en gruppe CrC6alkyl, C3-C7cycloalkyl eller halo; eller R19 er en gruppe med den almene formel (V) hvor R20, R21, Re og RF er som defineret ovenfor;
T er -N= eller -CR23=; R23 er H, halo, -CH3, eller -CN; R22 er H, halo, -CH3, eller -CN; q er 0, 1,2 eller 3.
2. Forbindelse med formel (I) ifølge krav 1, som er en forbindelse med formel (la), hvor det stereogene carboncenter på cycloalkylen-delen af ring A, som er bundet til gruppe W og er identificeret med nummer (1) nedenfor, har den absolutte konfiguration repræsenteret nedenfor:
(la) eller et farmaceutisk acceptabelt salt deraf.
3. Forbindelse med formel (I), ifølge krav 1 eller 2, som er en forbindelse med formel (Ib), hvor de stereogene carboncentre på cycloalkylen-delen af ring A, som er bundet til gruppe W og Y og er identificeret, respektivt, med numrene (1) og (2) nedenfor, har den absolutte konfiguration repræsenteret nedenfor:
(Ib) eller et farmaceutisk acceptabelt salt deraf.
4. Forbindelse med formel (I) ifølge et af kravene 1 til 3, hvor R1 er en gruppe med formel (Ile): eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelse med formel (I) ifølge et af kravene 1 til 4, hvor R1 er en gruppe med formel (llca) som defineret ovenfor, som er forbundet med gruppen Y via carbonatomet grænsende op til X2
og hvor X4 er et carbonatom, X5 er et nitrogenatom, X3 er et nitrogenatom og X2 er en -CH-gruppe, og R13 er hydrogen; hvor R11 er en gruppe:
hvor R25 eventuelt er til stede og repræsenterer en, to eller tre substituenter uafhængigt udvalgt fra listen bestående af: CrC6alkyl, (CrC3)haloalkyl, (Cr C4)hydroxyalkyl, C3-C7cycloalkyl, hydroxyl og halo; og hvor stjernen betegner bindingspunktet for R11-gruppen til resten af molekylet via X4; hvor R2 er et radikal med formel (I I Ib): (Nib)
ί hvor z1 = -CH-, z2= C, z3 og z4 er N og R17 er en gruppe med den almene formel (IV)
(IV) og hvor R20 er -CH3 eller -CH2OH, R21 er -CH3 og R18 er som defineret i krav 1.
6. Forbindelse med formel (I) ifølge et af kravene 1 til 4, hvor R1 er en gruppe med formel (llca) som defineret ovenfor, som er forbundet med gruppen Y via carbonatomet grænsende op til X2
og hvor X4 er et carbonatom, X5 er et nitrogenatom, X3 er et nitrogenatom og X2 er en -CH-gruppe, og R13 er hydrogen; hvor R11 er en gruppe:
hvor R25 eventuelt er til stede og repræsenterer en, to eller tre substituenter uafhængigt udvalgt fra listen bestående af: CrCealkyl, (CrC3)haloalkyl, (Cr C4)hydroxyalkyl, C3-C7cycloalkyl, hydroxyl og halo; og hvor stjernen betegner bindingspunktet for R11-gruppen til resten af molekylet via X4; hvor R2 er et radikal med formel (lllb):
(Hib) . hvor z1 = -CH-, z2= C, z3 og z4 er N og R17 er en gruppe med den almene formel (IV)
og hvor R20 er -CH3 eller -CH2OH, R21 er -CH3 og R18 er som defineret krav 1.
7. Forbindelse ifølge krav 1 udvalgt blandt: 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(2-pyrrolidin-1 -yl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1 S,4R)-4-{3-[2-(4-methyl-piperazin-1 -yl)-ethyl]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-(3-piperidin-1 -yl)- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-piperidin-4-yl)- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-((S)-3-pyrrolidin-2-yl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-(3-piperazin-1 -ylmethyl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-isopropylamino- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-((R)-3-pyrrolidin-2-yl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-methyl-piperazin-1 -ylmethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-morpholin-4-ylmethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-(3-pyrrolidin-1 -ylmethyl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-morpholin-4-ylmethyl-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(3-morpholin-4-ylmethyl-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(2-morpholin-4-ylmethyl-phenyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-(1 -methyl-piperidin-4-ylmethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1 S,4R)-4-{3-[1 -(2,2-difluor-ethyl)-piperidin-4-ylmethyl]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-[3-(4-hydroxypiperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(IS,4R)-4-{3-[(2-hydroxy-ethyl)-methyl-amino]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; l-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-hydroxy-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-hydroxy-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((R)-2-hydroxymethyl-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-hydroxymethyl-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(3-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 3-[3-tert-Butyl-5-(3-{(1 S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}- ureido)-pyrazol-1-yl]-benzoesyreethylester; 1-[5-tert-Butyl-2-(3-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}urea; 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethylsulfanyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[5-(2-Hydroxy-1,1 -dimethyl-ethyl)-2-p-tolyl-2H-pyrazol-3-yl]-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,3S)-3-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-indan-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((R)-3-hydroxy-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1 S,4R)-4-(3-piperidin-1-yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-{5-tert-Butyl-2-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}- 3- [(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1S,4R)-4-{3-[(2-dimethylamino-ethyl)-methyl-amino]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4-tetrahydro-naphthalen-1 -yl)-urea; 1 -[5-tert-Butyl-2-(3-piperidi n-1 -ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-[(1 S,4R)- 4- (3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1S,4R)-4-{3-[methyl-(2- morpholin-4-yl-ethyl)-amino]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4- tetrahydro-naphthalen-1-yl)-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((R)-1 -morpholin-4-yl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1 -morpholin-4-yl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1,2-dimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethoxymethyl)-phenyl]-2H-pyrazol-3-yl}-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-(3-[1,4]oxazepan-4-yl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-{3-[4-(2-hydroxy-ethyl)-piperazin-1-ylmethyl]-phenyl}-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-{5-tert-Butyl-2-[3-(4-hydroxy-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-{5-tert-Butyl-2-[3-(2-hydroxy-ethylsulfanyl)-phenyl]-2H-pyrazol-3-yl}-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-hydroxymethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4S)-4-(3-piperidin-1 -yl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(3-hydroxymethyl-4-methyl-piperazin-1 -ylmethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-(4-hydroxy-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1 -isopropyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1S,4R)-4-(3-dimethylamino- [1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((R)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1 -ethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1 -methyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-hydroxy-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((R)-3-hydroxy-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(4-hydroxymethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-1 -methyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-hydroxyethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -[(1 S,4R)-4-(3-Azepan-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-methyl-piperazine-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-methyl- [1.4] diazepan-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}urea; 1-[5-tert-Butyl-2-(4-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1-[5-tert-Butyl-2-(4-cyano-phenyl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4S)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[5-tert-Butyl-2-(4-hydroxy-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1 S,4R)-4-{3-[4-(1 -hydroxy-1 -methyl-ethyl)-piperidin-1 -yl]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-[(1 S,4R)-4-(3-pyrrolidin-1 -yl- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-(1 -dimethylamino-1 -methyl-ethyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((R)-3-hydroxymethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-hydroxymethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-(4-hydroxy-4-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-(1 -methyl-1 -pyrrolidin-1 -yl-ethyl)-[l,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((R)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-4-methyl-morpholin-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1 S,4R)-4-{3-[(S)-1 -(3-hydroxy-propyl)-pyrrolidin-2-yl]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4-tetrahydro-naphthalen-1 -yl)-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-hydroxy-methyl-1 -methyl-pyrrolidi n-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-(1,4-dimethyl-piperazin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1,4,4-trimethyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-1 -methyl-piperidin-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((R)-1 -methyl-piperidin-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((R)-1 -methyl-pyrrolidin-3-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((2S,4R)-4-fluor-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-3-hydroxymethyl-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((R)-3-hydroxymethyl-pyrrolidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-((1S,4R)-4-{3-[4-(2-hydroxy-ethyl)-piperazin-1 -yl]-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy}-1,2,3,4-tetrahydro-naphthalen-1-yl)-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1 -yl]-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-(cis-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(3-rnorpholin-4-ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-{5-tert-Butyl-2-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-(1 -dimethylamino-cyclopentyl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -[(1 S,4R)-4-(3-Amino-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-3-(5-tert-butyl-2-p-tolyl-2H-pyrazol-3-yl)-urea; 1-[5-tert-Butyl-2-(6-methyl-pyridin-3-yl)-2H-pyrazol-3-yl]-3-[(1S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-[(1 S,4R)-4-(3-diisopropylamino-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; N-(5-tert-Butyl-2-methoxy-3-{3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3- a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-ureido}-phenyl)- methansulfonamid; 1 -(5-tert-Butyl-2-p-tolyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[8-methyl-3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-{5-tert-Butyl-2-[4-(4-methyl-piperazin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}- 3- [(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -(3-tert-Butyl-1 '-methyl-1 'H-[1,4']bipyrazolyl-5-yl)-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1 -yl]-urea; 1 -[3-tert-Butyl-1 '-(2-dimethylamino-ethyl)-1 'H-[1,4']bipyrazolyl-5-yl]-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; N-[5-tert-Butyl-2-methoxy-3-(3-{(1S,4R)-4-[3-((S)-1-methyl-pyrrolidin-2-yl)- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-ureido)-phenyl]-methansulfonamid; 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-isoxazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)- [1.2.4] triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[3-tert-Butyl-1 '-(2-morpholin-4-yl-ethyl)-1 Ή-[1,4']bipyrazolyl-5-yl]-3- [(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -[3-tert-Butyl-1 '-(3-dimethylamino-propyl)-1 Ή-[1,4']bipyrazolyl-5-yl]-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -[3-tert-Buty I-1 '-(3-morpholin-4-yl-propyl)-1 Ή-[1,4']bipyrazolyl-5-yl]-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -{(1 S,4R)-4-[3-((2S,6R)-2,6-Dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-(3-fluor-5-morpholin- 4- yl-phenyl)-urea; 1-[5-tert-Butyl-2-(2-morpholin-4-yl-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea;
1 -Cyclopropyl-3-{(1 S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-{5-tert-Butyl-2-[-(2-dimethylamino-ethyl)-1 H-imidazol-4-yl]-2H-pyrazol-3-yl}-3-[(1 S,4R)-4-(3-piperidin-1 -yl-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy)-1,2,3,4-tetrahydro-naphthalen-1-yl]-urea; 1 -[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-1 -methyl-piperidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(2-morpholin-4-yl-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]- 1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{(1S,4R)-4-[3-(8-Aza-bicyclo[3.2.1]oct-8-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((R)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[3-tert-Butyl-1 '-(2-morpholin-4-yl-ethyl)-1 Ή-[1,4']bipyrazolyl-5-yl]-3-{(1 S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[3-tert-Butyl-1 '-(2-dimethylamino-ethyl)-1 'H-[1,4']bipyrazolyl-5-yl]-3-{(1 S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-methyl-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1-yl]-urea; 1-[5-tert-Butyl-2-(2-dimethylamino-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -[5-tert-Butyl-2-(2-piperidin-1 -yl-ethyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)- 2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-{5-tert-Butyl-2-[2-(4-methyl-piperazin-1-yl)-ethyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(3-morpholin-4-ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]- 1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-morpholin-4-yl-ethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -{5-tert-Butyl-2-[3-(2-pyrrolidin-1 -yl-ethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(ethyl-methyl-amino)-ethyl]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-piperidin-1-yl-ethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l-yl}-urea; 1-{5-tert-Butyl-2-[3-(2-[1,4]oxazepan-4-yl-ethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -(5-tert-Butyl-2-{3-[2-(4-methyl-[1,4]diazepan-1 -yl)-ethyl]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(2-hydroxy-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-3-methyl-morpholin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-(5-tert-Butyl-2-{2-[(2-dimethylamino-ethyl)-methyl-amino]-pyrimidin-4-yl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-3-methyl-morpholin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(2-morpholin-4-yl-ethyl)-2H-pyrazol-3-yl]-3-{1S,4R)-4-[3-((S)- 3-methyl-morpholin-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-{5-tert-Butyl-2-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}- 3- {(1 S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[5-tert-Butyl-2-(3-pyrrolidin-1 -ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)- 4- [3-((2S,6R)-2,6-dimethyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]- 1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(ethyl-methyl-amino)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((2S,6R)-2,6-dimethyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -{(1 S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2J3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea; 1-[5-tert-Butyl-2-(3-morpholin-4-yl-methyl-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{3-[(2-dimethylamino-ethyl)-methyl-amino]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-((R)-2-dimethylamino-1-methyl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-((S)-2-dimethylamino-1-methyl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[2-[3-(2-Dimethylamino-ethoxy)-phenyl]-5-(2-hydroxy-1,1 -dimethyl-ethyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-diethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-morpholin-4-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-piperidin-1-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{(1 SJ4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(4-methyl-piperazin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-{5-tert-Butyl-2-{3-[2-(4-fluorpiperidin-1-yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl}-3-{1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1 -(5-tert-Butyl-2-{3-[2-(4-methyl-[1,4]-diazepan-1 -yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-[1,4]oxazepan-4-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-3-{1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1 -(2-{3-[2-(8-Aza-bicyclo[3.2.1 ]oct-8-yl)-ethoxy]-phenyl}-5-tert-butyl-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(ethyl-methyl-amino)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-{5-tert-Butyl-2-(3-{2-[(2-methoxy-ethyl)-methyl-amino]-ethoxy}-phenyl}-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(4-methoxy-piperidin-1-yl-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-(5-tert-Butyl-2-{3-[2-(3-oxa-8-aza-bicyclo[3.2.1]oct-8-yl)-ethoxy]-phenyl}-2H-pyrazol-3-yl)-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)- [1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l-yl}-urea; 1-{5-tert-Butyl-2-[3-(4-methoxy-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}- 3- {(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-[5-tert-Butyl-2-(3-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-{5-tert-Butyl-2-[3-(4-fluor-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1-[5-tert-Butyl-2-(3-dimethylaminomethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)- 4- [3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l-yl}-urea; 1 -[5-tert-Butyl-2-(3-pyrrolidin-1 -ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l -yl}-urea; 1 -{(1 S,4R)-4-[3-(4-Aza-spiro[2.5]oct-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-3-{5-tert-butyl-2-[3-(2-morpholin-4-yl-ethoxy)-phenyl]-2H-pyrazol-3-yl}-urea; 1 -[5-tert-Butyl-2-(3-piperidi n-1 -ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -{5-tert-Butyl-2-[3-(4-methyl-[1,4]diazepan-1 -ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -{5-tert-Butyl-2-[3-((1 S,4S)-5-methyl-2,5-diaza-bicyclo[2.2.1 ]hept-2-ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(4-morpholin-4-ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-[5-tert-Butyl-2-(4-dimethylaminomethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -15-tert-Butyl-2-[4-(4-methyl-piperazin-1 -ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -{5-tert-Butyl-2-[4-(4-methyl-[1,4]diazepan-1 -ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{1S,4R)-4-[3-((S)-2-methyl-piperidin-1-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[4-(4-methoxy-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}- 3- {1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1 -[5-tert-Butyl-2-(4-pyrrolidin-1 -ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)- 4- [3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1 -[5-tert-Butyl-2-(4-piperidin-1 -ylmethyl-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1-yl}-urea; 1-{5-tert-Butyl-2-[4-(4-fluor-piperidin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-(5-tert-Butyl-2-{4-[(ethyl-methyl-amino)-methyl]-phenyl}-2H-pyrazol-3-yl)-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -y|)-[l ,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-[5-tert-Butyl-2-(4-{[(2-methoxy-ethyl)-methyl-amino]-methyl}-phenyl)-2H-pyrazol-3-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(2-dimethylamino-ethoxy)-phenyl]-2H-pyrazol-3-yl-3-{(1 S,4S)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydronaphthalen-1 -yl]-urea; 1 -[3-tert-Butyl-1 '-(2-dimethylamino-ethyl)-1 'H-[1,4']bipyrazolyl-5-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 yl}-urea; 1 -[3-tert-Butyl-1 '-(2-morpholin-4-yl-ethyl)-1 Ή-[1,4']bipyrazolyl-5-yl]-3-{(1 S,4R)-4-[3-((S)-2-methyl-piperidin-1 -yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-1 -yl}-urea; 1-{5-tert-Butyl-2-[3-(4-methyl-piperazin-1-ylmethyl)-phenyl]-2H-pyrazol-3-yl}-3-{(1 S,4R)-4-[3-((S)-1 -methyl-pyrrolidin-2-yl)-[1,2,4]triazolo[4,3-a]pyridin-6-yloxy]-1,2,3,4-tetrahydro-naphthalen-l-yl}-urea; og farmaceutisk acceptable salte deraf.
8. Farmaceutisk sammensætning omfattende en forbindelse ifølge et af de foregående krav 1 til 7, sammen med en eller flere farmaceutisk acceptable bærere.
9. Forbindelse ifølge et af kravene 1 til 7 til anvendelse ved behandling af sygdomme eller tilstande, som drager fordel af hæmning af p38-MAP-kinase-aktivitet.
10. Forbindelser ifølge et af kravene 1 til 7 til anvendelse ved behandling af sygdomme eller tilstande, som drager fordel af hæmning af p38-MAP-kinase-aktivitet ifølge krav 9, hvor sygdommene eller tilstandene er kronisk eosinofil pneumoni, asthma, COPD, respiratorisk distress-syndrom hos voksne (ARDS), exacerbation af luftvejs-hyperreaktivitet som en følge af en anden behandling med lægemidler eller luftvejssygdom, som er associeret med pulmonal hypertension.
11. Anvendelse af en forbindelse ifølge et af kravene 1 til 7 ved fremstilling af et medikament til behandling af sygdomme eller tilstande, som drager fordel af hæmning af p38-MAP-kinaseaktivitet.
12. Anvendelse ifølge krav 11, hvor sygdommen eller tilstanden er kronisk eosinofil pneumoni, asthma, COPD, respiratorisk distress-syndrom hos voksne (ARDS), exacerbation af luftvejs-hyperreaktivitet som en følge af en anden behandling med lægemidler eller luftvejssygdom, som er associeret med pulmonal hypertension.
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