DK3087070T3 - Pyrazolo[1,5-a]pyridinderivater og fremgangsmåder til deres anvendelse - Google Patents

Pyrazolo[1,5-a]pyridinderivater og fremgangsmåder til deres anvendelse Download PDF

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DK3087070T3
DK3087070T3 DK14824711.7T DK14824711T DK3087070T3 DK 3087070 T3 DK3087070 T3 DK 3087070T3 DK 14824711 T DK14824711 T DK 14824711T DK 3087070 T3 DK3087070 T3 DK 3087070T3
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fluoro
phenyl
pyrazolo
pyridin
carboxylic acid
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Robert L Hudkins
Allison L Zulli
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Ignyta Inc
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/415—1,2-Diazoles
    • A61K31/4162—1,2-Diazoles condensed with heterocyclic ring systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)

Claims (15)

1. Forbindelse med formel I: hvor
Ri er H; halo; -Ci-6alkyl; -Ci ealkoxy; eventuelt substitueret pyridyl; eventuelt substitueret pyrimidinyl; eventuelt substitueret pyrazinyl; eventuelt substitueret pyrazolyl; eventuelt substitueret imidazolyl; eventuelt substitueret isoxazolyl; eventuelt substitueret oxazolyl; eventuelt substitueret thiazolyl; eventuelt substitueret isothiazolyl; eventuelt substitueret morpholinyl; eventuelt substitueret piperazinyl, eventuelt substitueret piperidinyl; eventuelt substitueret tetrahydropyranyl; eventuelt substitueret pyrrolidinyl; tetrahydrothiopyranyl 1,1-dioxid; thiomorpholinyl 1,1-dioxid; pyrrolidinyl- on; piperidinyl-on; eventuelt substitueret -NH-aryl; eventuelt substitueret -NH-pyridyl; eventuelt substitueret -NH-pyrimidinyl; -C(0)NHCi-6alkyl; - C(0)N(Ci-6alkyl)2; -NHS(0)2Ci-6alkyl; -N(Ci-6alkyl)-S(0)2Ci-ealkyl; -NHC(0)Ci-6alkyl; -NCi-6alkylC(0)Ci-6alkyl; -NHC(0)OCi-6alkyl; -NCi-6alkylC(0)0Ci-6alkyl; -NHC(0)NHCi-6alkyl; -NCi-6alkylC(0)N(Ci-6alkyl)2; eventuelt substitueret -NHC(0)-piperazinyl; eller eventuelt substitueret -NCi-6alkylC(0)-piperazinyl; hver R2 er uafhængigt H, halo, -Ci-ealkyl, -Ci-ealkoxy, -OH, -O-alkaryl, eller trihaloalkyl; R3 er H eller halo; A er CR2 eller N; B er CR2 eller N; Q er -S(0)2aryl eventuelt substitueret med halo eller Ci-ealkyl; pyridyl eventuelt substitueret med halo eller -C(0)NHphenyl; pyrimidinyl; pyrazinyl; -C(0)-NHC(0)-alkaryl eventuelt substitueret med halo eller Ci-ealkyl; -C(S)-NHC(0)-alkaryl eventuelt substitueret med halo eller Ci-6alkyl; -C(0)-alkaryl eventuelt substitueret med halo eller Ci-ealkyl; -C(0)NH-aryl eventuelt substitueret med halo, Ci-6alkyl eller Ci-6alkoxy; -C(0)-0-aryl eventuelt substitueret med halo, Ci-6alkyl eller Ci-6alkoxy; eller
hvor X er CR.6, hvor Re er H eller Ci-ealkyl; eller N; R4 er H; Ci-ealkoxy; halo; -OCi-ealkylen-O-Ci-ealkyl; -NHCi-ealkyl; eller -N(Ci-6alkyl)2; R5 er aryl eventuelt substitueret med halo eller Ci-ealkyl; eller alkaryl eventuelt substitueret med halo eller Ci-ealkyl; eller
hvor Y er C eller N; R7 er H eller Ci-ealkyl; Rs er H; Ci-ealkylen-O-Ci-ealkyl; Ci-ealkyl; Ci-ealkylen-O-Ci-ealkaryl; eller Ci-ealkylen-OH; Rg er H, Ci-ealkyl; eller halo; eller
hvor Rio er H; halo; eller Ci-ealkyl; eller hvor
Ru er H eller Ci-ealkyl; R12 er H; Ci-6alkyl; eller aryl eventuelt substitueret med halo; R13 er H; Ci-6alkyl; eller trihaloCi-6alkyl; eller hvor
R14 er H; Ci-ealkyl; eller halo; eller et farmaceutisk acceptabelt salt deraf.
2. Forbindelsen ifølge krav 1, hvor A er CR2, eller et farmaceutisk acceptabelt salt deraf.
3. Forbindelsen ifølge et hvilket som helst af de foregående krav, hvor B er CR2, eller et farmaceutisk acceptabelt salt deraf.
4. Forbindelsen ifølge et hvilket som helst af kravene 2 eller 3, hvor hver R2 uafhængigt er H eller halo, eller et farmaceutisk acceptabelt salt deraf.
5. Forbindelsen ifølge krav 4, hvor halo er F, eller et farmaceutisk acceptabelt salt deraf.
6. Forbindelsen ifølge et hvilket som helst af de foregående krav, hvor R3 er H, eller et farmaceutisk acceptabelt salt deraf.
7. Forbindelsen ifølge et hvilket som helst af de foregående krav, hvor Q er
eller et farmaceutisk acceptabelt salt deraf.
8. Forbindelsen ifølge krav 7, hvor Y er C; R7 er H; er H, Ci-ealkylen-O-Ci ealkyl, eller Ci ealkyl; og R9 er Halo, eller et farmaceutisk acceptabelt salt deraf.
9. Forbindelsen ifølge et hvilket som helst af de foregående krav, hvor Ri er eventuelt substitueret imidazolyl, eller et farmaceutisk acceptabelt salt deraf.
10. Forbindelsen ifølge krav 1, hvor forbindelsen er valgt fra 3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3- fluor-4-(pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-pyridin-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-pyrazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-(2-ethoxy-ethyl)-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-pyrazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-pyrazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(lH-pyrazol-3-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-oxazol-5-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-isothiazol-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5- carboxylsyre [3-fluor-4-(6-isothiazol-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)- phenyl]-amid; l-(2-ethoxy-ethyl)-3-(4-fluor-phenyl)-2,4-dioxo-1,2,3,4-tetrahyd ro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-morpholin-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-morpholin-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-d ioxo-1,2,3,4-tetrahyd ro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-morpholin-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-methyl-4-(6-morpholin-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-methyl-4-(6-morpholin-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5- carboxylsyre {4-[6-(4,4-difluor-piperidin-l-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluor-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(3,3-difluor-pyrrolidin-l-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluorphenyl>- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(3,3-difluor-pyrrolidin-l-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluor-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l,l-dioxo-thiomorpholin-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3- fluorphenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l,l-dioxo-thiomorpholin-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluor-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(2-oxo-pyrrolidin-l-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(2-oxo-pyrrolidin-l-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(pyrimidin-2-ylamino)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(pyrimidin-2-ylamino)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(pyridin-2-ylamino)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(pyridin-2-ylamino)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5- carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-l-methyl-2,4-dioxo-1,2,3,4-tetrahyd ro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-(2-benzyloxy-ethyl)-3-(4-fluor-phenyl-)-2,4-dioxo-1,2,3,4-tetrahyd ro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-l-(2-hydroxy-ethyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-oxazol-2-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(3-methyl-3H-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-thiazol-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-thiazol-5-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-thiazol-5-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-thiazol-4-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3- fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>- amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-methyl-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-methyl-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin- 4-yloxy]-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {6-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-pyridin-3-yl}- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {6-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-pyridin-3-yl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-methoxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-hydroxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-benzyloxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-hydroxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-2,4-dioxo-l-pentyl-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {5-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-pyridin-2-yl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3- trifluormethyl-phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5- carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-trifluormethyl-phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- 2- trifluormethyl-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-pyrimidin-2-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3- (4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-pyrimidin-2-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-pyrazin-2-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-pyrazin-2-yl-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(6-methyl-pyridin-2-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>- amid; 3- (4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(6-methyl-pyridin-2-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 4- (2-fluor-4-{[3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydropyrimidin-5-carbonyl]-amino>-phenoxy)-pyrazolo[l,5-a]pyridin-6-carboxylsyre-dimethylamid; 4-(4-{[l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5- carbonyl]-amino>-2-fluor-phenoxy)-pyrazolo[l,5-a]pyridin-6-carboxylsyre- dimethylamid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-methanesulfonylamino-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [3-fluor-4-(6-methanesulfonylamino-pyrazolo[l,5-a]pyridin-4-yloxy)-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [4-(6-acetylamino-pyrazolo[l,5-a]pyridin-4-yloxy)-3-fluor-phenyl]-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre [4-(6-acetylamino-pyrazolo[l,5-a]pyridin-4-yloxy)-3-fluor-phenyl]-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(acetyl-methyl-amino)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluor-phenyl>- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(acetyl-methyl-amino)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluor-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(3,3-dimethyl-urea)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluor-phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(3,3-dimethyl-ureido)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-fluorphenyl}-amid; [4-(4-{[ l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5- carbonyl]-amino}-2-fluor-phenoxy)-pyrazolo[l,5-a]pyridin-6-yl]- carbaminsyremethylester; [4-(2-fluor-4-{[3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydropyrimidin-5-carbonyl]-amino}-phenoxy)-pyrazolo[l,5-a]pyridin-6-yl]-carbaminsyremethylester; og 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre (3-fluor-4-{6-[(4-methyl-piperazine-l-carbonyl)-amino]-pyrazolo[l,5-a]pyridin-4-yloxy>-phenyl)-amid; eller et farmaceutisk acceptabelt salt deraf.
11. Forbindelsen ifølge krav 1, hvor forbindelsen er valgt fra l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-l-methyl-2,4-dioxo-l, 2,3,4-tetrahyd ro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-(2-benzyloxy-ethyl)-3-(4-fluor-phenyl-)-2,4-dioxo-l,2,3,4-tetrahydro- pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; 3-(4-fluor-phenyl)-l-(2-hydroxy-ethyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(3-methyl-3H-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-methyl-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl>-amid; 3- (4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-methyl-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyndin- 4- yloxy]-phenyl}-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}- amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-methoxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid; l-ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-hydroxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-benzyloxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-hydroxy-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 3-(4-fluor-phenyl)-2,4-dioxo-l-pentyl-1,2,3,4-tetrahyd ro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl}-amid; 1- ethyl-3-(4-fluor-phenyl)-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-trifluormethyl-phenyl>-amid; 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-3-trifluormethyl-phenyl>-amid; og 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]- 2- trifluormethyl-phenyl>-amid; eller et farmaceutisk acceptabelt salt deraf.
12. Forbindelsen ifølge krav 1, der er 3-(4-fluor-phenyl)-l-isopropyl-2,4-dioxo-l,2,3,4-tetrahydro-pyrimidin-5-carboxylsyre {3-fluor-4-[6-(l-methyl-lH-imidazol-4-yl)-pyrazolo[l,5-a]pyridin-4-yloxy]-phenyl>-amid, eller et farmaceutisk acceptabelt salt deraf.
13. Farmaceutisk sammensætning, omfattende forbindelsen ifølge et hvilket som helst af de foregående krav, og ét eller flere farmaceutisk acceptable bærere.
14. Forbindelsen ifølge et hvilket som helst af kravene 1-12, eller farmaceutisk sammensætning ifølge krav 13, til anvendelse i en fremgangsmåde til behandling af cancer hos en patient.
15. Forbindelsen eller farmaceutisk sammensætning til anvendelse ifølge krav 14, hvor canceren er leukæmi, koloncancer, melanom, nyrecancer, levercancer, mavecancer, brystcancer, eller hjernecancer.
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