DK2763982T3 - Substituerede benzylindazoler til anvendelse som bub1-kinasehæmmere til behandling af hyperproliferative sygdomme - Google Patents

Substituerede benzylindazoler til anvendelse som bub1-kinasehæmmere til behandling af hyperproliferative sygdomme Download PDF

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DK2763982T3
DK2763982T3 DK12766997.6T DK12766997T DK2763982T3 DK 2763982 T3 DK2763982 T3 DK 2763982T3 DK 12766997 T DK12766997 T DK 12766997T DK 2763982 T3 DK2763982 T3 DK 2763982T3
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indazol
pyridin
pyrimidin
methoxy
alkyl
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Marion Hitchcock
Anne Mengel
Vera Pütter
Gerhard Siemeister
Antje Margret Wengner
Hans Briem
Knut Eis
Volker Schulze
Amaury Ernesto Fernandez-Montalvan
Stefan Prechtl
Simon Holton
Philip Lienau
Cornelia Preusse
Mark Jean Gnoth
Jörg Fanghänel
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Bayer Pharma AG
Bayer Ip Gmbh
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Claims (34)

1. Forbindelse med formel (I)
hvor R1 er hydrogen, halogen, l-3C-alkyl, R2/R3 uafhængigt af hinanden er hydrogen, halogen, cyano, hydroxy l-6C-halogenalkyl, l-6C-halogenalkoxy, l-6C-alkoxy, R4 uafhængigt er hydrogen, hydroxy, halogen, cyano, NO2, 1-6C-alkyl, 2-6C-alkenyl, 2-6C-alkynyl, l-6C-halogenalkyl, 1-6C-hydroxyalkyl, l-6C-alkoxy, -0-(2-6C-alkylen)-0-C(0)-(1-6C-alkyl) , l-6C-halogenalkoxy, -C(0)0R9, - (l-6C-alkylen) -C (0) OR9, -C (0) - (l-6C-alkyl) , -C (0) NR10Rn, 3-7C-cycloalkyl, -S-(1-6C- halogenalkyl) , SF5, -SO2NH- (3-7C-cycloalkyl) , -SChNR^R11, NR10R41, heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-4C-alkyl, l-6C-halogenalkyl, 1-6C-halogenalkoxy, C(0)0R9, C(O)NR10R41, hvor to af R2, R3 (R4)n, når de er i ortho-positionen i forhold til hinanden, sammen med de to carbonatomer, hvortil de er bundet, kan danne en heterocyklisk 5-, 6- eller 7-leddet ring, der indeholder 1 eller 2 heteroatomer valgt blandt 0 eller N og eventuelt indeholder en yderligere dobbeltbinding og/eller eventuelt er substitueret med en oxo (=0)-gruppe og/eller en l-4C-alkylgruppe, n er 0-3, R6 er (a) hydrogen; (b) hydroxy; (c) cyano; (d) l-6C-alkoxy eventuelt substitueret uafhængigt en eller flere gange med (dl) OH, (d2) -O-(l-6C-alkyl), (d3) C (O) OR9, (d4 ) C (O) NR10R11, (d5) NR10Rn, (d 6) -S-(l-6C-alkyl), (d7) -S (O)-(l-6C-alkyl), (d8) -SO2-(l-6C-alkyl), (d 9) SO2NR10R11, (dlO) heterocyclyl, der eventuelt er substitueret med C(O)OR9, eller oxo (=0) , (dll) heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-4C-alkyl, l-6C-halogenalkyl, 1-6C-halogenalkoxy, C(0)0R9, C(O)NR10R11, (l-6C-alkylen)-0-(1-6C- alkyl), (e) SO2NR10R11, (f) 3-7C-cycloalkoxy, (g) l-6C-halogenalkoxy, (h) COOR9, (i) -C (0) NR10Rn,
(j) -O-heteroaryl eventuelt substitueret med CN, * i (k) > hvor * er bindingspunktet, (l) -0-(2-6C-alkylen)-0-(l-6C-alkyl), der eventuelt er substitueret med hydroxy, NH(C0)0R9, R7 er (a) hydrogen, (b) l-6C-alkyl, der eventuelt er substitueret med heteroaryl, (c) l-6C-halogenalkyl, (d) l-6C-hydroxyalkyl,
H (e) hvor * er bindingspunktet, (f) -C (0)-(l-6C-alkyl), (g) -C (0)- (l-6C-alkylen)-0-(l-6C-alkyl), (h) -C (0)-(l-6C-alkylen)-0-(2-6C-alkylen)-0-(1 -6C-alkyl), (i) -C(0)-heterocyclyl, (j) benzyl, hvor phenylringen eventuelt er substitueret med 1- 5 substituenter, der er valgt uafhængigt fra gruppen, der består af hydrogen, halogen, l-4C-alkyl, l-4C-halogenalkyl, l-4C-alkoxy, 1-4C-halogenalkoxy, cyano, C(0)0R9, (k) heteroaryl eller eventuelt R6 og R7 sammen med nitrogenatomet, hvortil R7 er bundet, danner en 6-leddet ring, der kan indeholde ét yderligere heteroatom valgt fra gruppen, der består af 0, S, N, og som eventuelt er substitueret med (l-6C-alkyl)-OH, (1-6C-alkyl) -NR10R11, R8 er hydrogen, halogen, hydroxy, cyano, l-6C-alkyl, 1-6C-hydroxyalkyl, l-6C-halogenalkyl, l-6C-halogenalkoxy, C(0)0R9, C (0) NR10Rn, m er 0-4, R9 er (a) hydrogen, (b) l-6C-alkyl, der eventuelt er substitueret med hydroxy, R10, R11 uafhængigt af hinanden er hydrogen, l-4C-alkyl, 1-4C- hydroxyalkyl, l-4C-alkoxy, -(CO)-(l-6C-alkyl), CHO, COOR9 eller sammen med nitrogenatomet, hvortil de er bundet, danner en 4- 6-leddet heterocyklisk ring, der eventuelt indeholder ét yderligere heteroatom valgt fra gruppen, der består af 0, S eller N, og eventuelt er substitueret med 1-2 fluoratomer eller COOR9, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
2. Forbindelse med formel (I) ifølge krav 1, hvor R1 er hydrogen, halogen, l-3C-alkyl, R2/R3 uafhængigt af hinanden er hydrogen, halogen, cyano, 1-6C-halogenalkyl, l-6C-halogenalkoxy, R4 uafhængigt er hydrogen, halogen, cyano, l-6C-alkyl, 2-6C-alkenyl, l-6C-halogenalkyl, l-6C-hydroxyalkyl, l-6C-alkoxy, 1-6C-halogenalkoxy, -C(0)0R9, - (l-6C-alkylen) -C (0) OR9, —C (0) — (1 — 6C-alkyl), -C (0) NR10Rn, 3-7C-cycloalkyl, - S-(1-6C- halogenalkyl) , SF5, -SO2NH- (3-7-cycloalkyl) , -SO2NR10R11, heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-4C-alkyl, l-6C-halogenalkyl, 1-6C-halogenalkoxy, C(0)0R9, C(O)NR10R11, hvor to af R2, R3 (R4)n, når de er i ortho-positionen i forhold til hinanden, sammen med de to carbonatomer, hvortil de er bundet, kan danne en heterocyklisk 5-, 6- eller 7-leddet ring, der indeholder 1 eller 2 heteroatomer valgt blandt 0 eller N, og eventuelt en yderligere dobbeltbinding og/eller en carbonylgruppe og/eller en l-4C-alkylgruppe, n er 0-3, R6 er (a) hydrogen; (b) hydroxy; (c) cyano; (d) l-6C-alkoxy eventuelt substitueret med (dl) 1-2 OH, (d2) NR10Rn, (d3) SO2NR10R11, (d4) heterocyclyl, (d5) heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-4C-alkyl, l-6C-halogenalkyl, 1-6C-halogenalkoxy, C (O) OR9, C(O)NR10R11, (e) SO2NR10R11, (f) 3-7C-cycloalkoxy, (g) l-6C-halogenalkoxy, (h) -C (O) NR10Rn, (i) -O-heteroaryl eventuelt substitueret med CN, (j)
> hvor * er bindingspunktet, R7 er (a) hydrogen, (b) l-6C-alkyl, der eventuelt er substitueret med heteroaryl, (c) l-6C-halogenalkyl, (d) l-6C-hydroxyalkyl, (e)
' hvor * er bindingspunktet, (f) -C (O)-(l-6C-alkyl), (g) -C (O)-(l-6C-alkylen)-O-(l-6C-alkyl), (h) -C(O)-(l-6C-alkylen)-O-(l-6C-alkylen)-O-(l-6C-alkyl) , (i) -C (O)-heterocyclyl, (j) benzyl, hvor phenylringen eventuelt er substitueret med 1-5 substituenter, der er valgt uafhængigt fra gruppen, der består af hydrogen, halogen, l-4C-alkyl, l-4C-halogenalkyl, 1-4C-alkoxy, l-4C-halogenalkoxy, cyano, C(0)0R9, (k) heteroaryl, eller eventuelt R6 og R7 sammen med nitrogenatomet, hvortil de er bundet, danner en 6-leddet ring, der kan indeholde ét yderligere heteroatom valgt fra gruppen, der består af 0, S, N, og eventuelt er substitueret med hydroxy-(l-6alkyl), R8 er hydrogen, halogen, cyano, l-6C-halogenalkyl, 1-6C-halogenalkoxy, C(0)0R9, C(O)NR10R11, m er 0-4, R9 er (a) hydrogen, (b) l-6C-alkyl, der eventuelt kan være substitueret med hydroxy, R10, R11 uafhængigt af hinanden er hydrogen, l-4C-alkyl, 1-4C- hydroxyalkyl, l-4C-alkoxy eller sammen med nitrogenatomet, hvortil de er bundet, danner en 5-6-leddet heterocyklisk ring, der eventuelt indeholder ét yderligere heteroatom valgt fra gruppen, der består af 0, S eller N, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
3. Forbindelse med formel (I) ifølge krav 1, hvor R1 er hydrogen, halogen, l-3C-alkyl, R2/R3 uafhængigt af hinanden er hydrogen, halogen, cyano, hydroxy, l-3C-halogenalkyl, l-3C-halogenalkoxy, l-3C-alkoxy, R4 uafhængigt er hydrogen, hydroxy, halogen, cyano, NO2, 1-3C-alkyl, 2-3C-alkenyl, 2-3C-alkynyl, l-3C-halogenalkyl, 1-3C-hydroxyalkyl, l-3C-alkoxy, -0-(2-3C-alkylen)-0-C(0)-(1-3C-alkyl) , l-3C-halogenalkoxy, -C(0)0R9, - (l-3C-alkylen) -C (0) OR9, -C (0) - (1-3C-alkyl) , -C (0) NR10Rn, 3-7C-cycloalkyl, -S-(1-3C- halogenalkyl) , SF5, -SO2NH- (3-7C-cycloalkyl) , -SCgNR^R11, NR10R11, heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-3C-alkyl, l-3C-halogenalkyl, 1-3C-halogenalkoxy, C(0)0R9, C(O)NR10R11, hvor to af R2, R3 (R4)n, når de er i ortho-positionen i forhold til hinanden, sammen med de to carbonatomer, hvortil de er bundet, kan danne en heterocyklisk 5-, 6- eller 7-leddet ring, der indeholder 1 eller 2 heteroatomer valgt blandt 0 eller N, og eventuelt indeholder en yderligere dobbeltbinding og/eller eventuelt er substitueret med en oxo (=0)-gruppe og/eller en l-3C-alkylgruppe, n er 0-3, R6 er (a) hydrogen; (b) hydroxy; (c) cyano; (d) l-6C-alkoxy, der eventuelt er substitueret uafhængigt en eller flere gange med (dl) OH, (d2) -0-(l-3C-alkyl), (d3) C (0) OR9, (d4 ) C (0) NR10R11, (d5) NR10Rn, (d 6) -S-(l-3C-alkyl), (d7) -S (0)-(l-3C-alkyl), (d8) -SO2-(l-3C-alkyl), (d 9) SO2NR10R11, (dlO) heterocyclyl, der eventuelt er substitueret med C(0)0R9, eller oxo (=0) , (dll) heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-3C-alkyl, l-3C-halogenalkyl, 1-3C-halogenalkoxy, C(0)0R9, C(0)NR1°R11, (l-3C-alkylen)-0-(1-3C- alkyl), (e) SO2NR10R11, (f) 3-7C-cycloalkoxy, (g) l-6C-halogenalkoxy, (h) C00R9, (i) -C (0) NR10Rn, (j) -0-heteroaryl, der eventuelt er substitueret med CN, (k)
' hvor * er bindingspunktet, (l) -0-(2-3C-alkylen)-0-(1—3C—alkyl), der eventuelt er substitueret med hydroxy, NH(C0)0R9, R7 er (a) hydrogen, (b) l-3C-alkyl, der eventuelt er substitueret med heteroaryl (c) l-3C-halogenalkyl, (d) l-3C-hydroxyalkyl, (e)
' hvor * er bindingspunktet, (f) -C (0)-(1-3C-alkyl), (g) -C (0)-(l-3C-alkylen)-0-(l-3C-alkyl), (h) -C (0)-(l-3C-alkylen)-0-(2-3C-alkylen)-0-(l-3C-alkyl) , (i) -C (0)-heterocyclyl, (j) benzyl, hvor phenylringen eventuelt er substitueret med 1-5 substituenter, der er valgt uafhængigt fra gruppen, der består af hydrogen, halogen, l-4C-alkyl, l-4C-alkoxy, l-4C-halogenalkoxy, cyano, C (0) OR9, (k) heteroaryl, eller eventuelt R6 og R7 sammen med nitrogenatomet, hvortil R7 er bundet, danner en 6-leddet ring, der kan indeholde ét yderligere heteroatom valgt fra gruppen, der består af 0, S, N, og der eventuelt er substitueret med (l-3C-alkyl)-OH, (1-3C-alkyl) -NR10Rn, R8 er hydrogen, halogen, hydroxy, cyano, l-3C-alkyl, 1-3C-hydroxyalkyl, l-3C-halogenalkyl, l-3C-halogenalkoxy, C(0)0R9, C (0) NR10Rn, m er 0-4, R9 er (a) hydrogen, (b) l-3C-alkyl, der eventuelt er substitueret med hydroxy, R10, R11 uafhængigt af hinanden er hydrogen, l-3C-alkyl, 1-3C- hydroxyalkyl, l-3C-alkoxy, -(CO)-(l-3C-alkyl), CHO, COOR9 eller sammen med nitrogenatomet, hvortil de er bundet, danner en 4- 6-leddet heterocyklisk ring, der eventuelt indeholder ét yderligere heteroatom valgt fra gruppen, der består af 0, S eller N, der eventuelt er substitueret med 1-2 fluoratomer eller COOR9, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
4. Forbindelse med formel (I) ifølge krav 1, hvor R1 er hydrogen, l-3C-alkyl, R2/R3 uafhængigt af hinanden er hydrogen, halogen, cyano, hydroxy, l-4C-halogenalkyl, l-4C-alkoxy, R4 uafhængigt er hydrogen, hydroxy, halogen, cyano, l-4C-alkyl, 2-4C-alkenyl, 2-4C-alkynyl, l-4C-halogenalkyl, 1-4C- hydroxyalkyl, l-4C-alkoxy, -0-(2-4C-alkylen)-0-C(0)-(1-4C-alkyl) , l-4C-halogenalkoxy, -C(0)0R9, - (l-4C-alkylen) -C (0) OR9, -C (0) - (l-4C-alkyl) , -C (0) NR10Rn, 3-7C-cycloalkyl, -S-(1-4C- halogenalkyl) , SFs, -SO2NH- (3-7C-cycloalkyl) , -SO2NR10R41, NR10R41, heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-4C-alkyl, l-4C-halogenalkyl, 1-4C-halogenalkoxy, C(0)0R9, C(O)NR10R41, hvor to af R2, R3 (R4)n, når de er i ortho-positionen i forhold til hinanden, sammen med de to carbonatomer, hvortil de er bundet, kan danne en heterocyklisk 5-, 6- eller 7-leddet ring, der indeholder 1 eller 2 heteroatomer valgt blandt 0 eller N, og eventuelt indeholder en yderligere dobbeltbinding og/eller eventuelt er substitueret med en oxo (=0)-gruppe og/eller en l-4C-alkylgruppe, n er 0-3, R6 er (a) hydrogen; (b) hydroxy; (d) l-4C-alkoxy, der eventuelt er substitueret uafhængigt en eller flere gange med (dl) OH, (d2) -0-(l-4C-alkyl), (d3) C (0) OR9, (d4 ) C (0) NR10R41, (d5) NR10Rn, (d6) -S-(l-4C-alkyl) , (d7) -S (O)- (l-4C-alkyl), (d8) -SO2-(l-4C-alkyl) , (d 9) SO2NR10R11, (dlO) heterocyclyl, der eventuelt er substitueret med C(O)OR9, eller oxo (=0) , (dll) heteroaryl, der eventuelt er substitueret uafhængigt en eller flere gange med cyano, l-4C-alkyl, l-4C-halogenalkyl, 1-4C-halogenalkoxy, C(0)0R9, C(O)NR10R11, (l-4C-alkylen)-0-(1-4C- alkyl), (e) SO2NR10R11, (f) 3-7C-cycloalkoxy, (g) l-6C-halogenalkoxy, (h) COOR9, (i) -C (O) NR10Rn, (j) -O-heteroaryl, der eventuelt er substitueret med CN, (k)
> hvor * er bindingspunktet, (l) -O-(2-4C-alkylen)-O-(l-4C-alkyl), der eventuelt er substitueret med hydroxy, NH(CO)OR9, R7 er (a) hydrogen, (b) (l-4C-alkyl)-heteroaryl, (c) l-4C-halogenalkyl, (d) l-4C-hydroxyalkyl, (e)
> hvor * er bindingspunktet, (f) -C (0)-(l-4C-alkyl), (g) -C (0)-(l-4C-alkylen)-0-(l-4C-alkyl), (h) -C(0)-(l-4C-alkylen)-0-(2-4C-alkylen)-0-(l-4C-alkyl), (i) -C(0)-heterocyclyl, (j) benzyl, hvor phenylringen eventuelt er substitueret med 1-5 substituenter, der er valgt uafhængigt fra gruppen, der består af hydrogen, halogen, l-4C-alkyl, l-4C-alkoxy, 1-4C-halogenalkoxy, cyano, C(0)0R9, (k) heteroaryl, eller eventuelt R6 og R7 sammen med nitrogenatomet, hvortil R7 er bundet, danner en 6-leddet ring, der kan indeholde ét yderligere heteroatom valgt fra gruppen, der består af 0, S, N, og der eventuelt er substitueret med (l-4C-alkyl)-OH, (1-4C-alkyl) -NR10R41, R8 er hydrogen, halogen, hydroxy, cyano, C(O)NR10R11, 1-4C- alkyl, l-4C-hydroxyalkyl, l-4C-halogenalkyl, 1-4C- halogenalkoxy, m er 0-2, R9 er hydrogen, l-4C-alkyl, der eventuelt er substitueret med hydroxy, R10, R11 uafhængigt af hinanden er hydrogen, l-4C-alkyl, 1-4C- hydroxyalkyl, l-4C-alkoxy, -C(0)-(l-4C-alkyl) eller COOR9 eller sammen med nitrogenatomet, hvortil de er bundet, danner en 4- 6-leddet heterocyklisk ring, der eventuelt indeholder ét yderligere heteroatom valgt fra gruppen, der består af 0, S eller N, der eventuelt er substitueret med 1-2 fluoratomer eller COOR9, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
5. Forbindelse med formel (I) ifølge krav 1, hvor R1 er hydrogen, R2/R3 uafhængigt er hydrogen, fluor, chlor, brom, cyano, hydroxy, CF3, -O-CH3 eller -O-CH2-CF3, R4 uafhængigt af hinanden er hydrogen, fluor, chlor, brom eller rod, cyano, NO2, hydroxy, -CH3, -C3H7, cyclopropyl, 1-propenyl, - C=CH, -CF3, -CH2-OH, -CH2-CH2-OH, -C(CH3)2-OH, -ch2-c (CH3) 2-OH, -C (CH3) 2-CH2-OH, -OCH3, -O-CH2-CH3, -OCF3, -OCF2H, -OCH2CF3, -0-(CH2)-0-C (0)-CHs, -C(0)CH3, -C00H, -C(0)0CH3, -C(0)0C2Hs, C (0) 0C (CH3) 3, -CH2-COOH, -CH2-COOC2H5, -c (CH3) 2-COOC2H5, -C(0)NH2, -C (0)NH (CH3) , -C(0)N(CH3)2, -c (0)NH-(CH2) 2-OH, -C (0) - (N- morpholinyl), -S02-NH-cyclopropyl, -SO2-(N-morpholino), NH2, NH-C(0) (CH3) , 5-methyloxadiazol-3-yl, N-pyrrolyl, N-pyrazolyl, -S-CF3, SFs, hvor to af R2, R3 (R4)n, når de er i ortho-positionen i forhold til hinanden, sammen danner -O-CH2-CH2-CH2-0-, -O-CH2-CH2-, - (CH3) C=CH- (C=0) -o-, -CH2- (C=0) -o-, -(ch2)2-(C=0)-NH-, der sammen med de to carbonatomer, hvortil de er bundet, danner en 5-, 6- eller 7-leddet ring, n er 0, 1, 2, 3, R6 er hydrogen, hydroxy, cyano, -O-cyclopropyl, -OCH3, -OCF3, -OCF2H, -OCH2CF3, -0- (CH2) 2-OH, -0-(CH2) 2-NH2, -0 (CH2) 2-N (CH3) 2, - 0-(CH2) 2-O-CH3, -0- (CH2) 2-0- (CH2) 2-OH, -O-CH2-CH (OH)-CH2OH, -0- CH2-CH (OH)-CH2-NH-C (0) OC (CH3) 3, -O-CH2-COOH, -O-CH2-COOC2H5, C(0)NH2, -O-CH2-C (0) - (3-fluor-N-azetidin) , -0-CH2-C (0) - (3,3- dif luor-N-azetidin) , -0-CH2-CH (OH)-CH2-N-piperidinyl, -0- (CH2)2(morpholin-4-yl), -0-CH2-(morpholin-2-yl), -0-CH2- (morpholin-2-yl-4-tert-butoxycarboxylat), -0-CH2-(pyrrolidin-2-on-5-yl) , -0-(CH2) 2-S-CH3, -0-(CH2) 2-SO-CH3, -0-(CH2) 2-SO2-CH2, - O-CH2-SO2NH2, -SO2-CH (CH3) 2,
hvor * er bindingspunktet, -0-(CH2)2-tetrazolyl, -0-CH2-tetrazolyl, -0- pyridin-4-yl, -0-(3-cyanopyridin-4-yl) eller -0-CH2- (oxadiazol) -CH2-O-CH3, R7 er hydrogen, methyl, difluormethyl, hydroxyethyl,
hvor * er bindingspunktet, -(CH2)2~ tetrazolyl, pyridin-4-yl, -C(0)-tetrahydropyran-4-yl, -C(0)-CH2-O-CH3, -C (0) -CH3, -C (0) CH2-O-(CH2) 2-O-CH3, C (0) och2-ch=ch2 eller benzyl, der eventuelt er substitueret en eller flere gange med fluor, chlor, brom, cyano, methyl, difluormethyl, methoxy, ethoxy, difluormethoxy, trifluormethoxy, -O-CH2-CF3, -C(0)0CH3, eller eventuelt R6 og R7 sammen med nitrogenatomet, hvortil R7 er bundet, danner en 6-leddet ring, der kan indeholde ét yderligere heteroatom valgt fra gruppen, der består af 0, S, N, og som yderligere eventuelt er substitueret med -CH2-OH eller -CH2-NH-CH0, R8 er hydrogen, fluor, hydroxy, cyano, CH3, CF3, CH2-OH, OCH3, C (0) OH, C(0)0CH3, C(0)0C2H5, C (0) 0 (CH2) 2-OH, C(0)NH2, C(0)NHCH3, m er 0, 1 eller 2, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
6. Forbindelse med formel (I)
hvor R1, R2, R3, n, R6, R7, R8 og m har betydningerne ifølge krav 5, og R4 uafhængigt af hinanden er hydrogen, fluor, chlor, brom eller rod, cyano, NO2, hydroxy, -CH3, -C3H7, cyclopropyl, 1-propenyl, - C=CH, -CF3, -CH2-OH, -CH2-CH2-OH, -C(CH3)2-OH, -ch2-c (CH3) 2-oh, -C (CH3) 2-CH2-OH, -OCH3, -0-CH2-CH3, -OCF3, -OCF2H, -OCH2CF3, -0-(CH2)-0-C (0)-CH3, -C(0)CH3, -C00H, -C(0)0CH3, -C(0)0C2H5, C (0) OC (CH3) 3, -CH2-COOH, -CH2-COOC2H5, -c (CH3) 2-COOC2H5, -C(0)NH2, -C (0)NH (CH3) , -C(0)N(CH3)2, -c (0)NH-(CH2) 2-oh, -C (0) - (N- morpholinyl), -S02-NH-cyclopropyl, -SO2-(N-morpholino), NH2, NH-C(0) (CH3) , 5-methyloxadiazol-3-yl, N-pyrrolyl, N-pyrazolyl og -S-CF3, SF5, hvilken gruppe eventuelt er substitueret en eller flere gange identisk eller forskelligt med en substituent valgt blandt: hydroxy, halogen, cyano, l-6C-alkyl, l-4C-halogenalkyl og 1-6C-alkoxy, hvor to af R2, R3 (R4)n, når de er i ortho-positionen i forhold til hinanden, sammen danner -O-CH2-CH2-CH2-O-, -O-CH2-CH2-, (CH3) C=CH-(C=0)-0-, —CH2— (C=0) -0-, - (CH2) 2- (C=0) -NH-, der sammen med de to carbonatomer, hvortil de er bundet, danner en 5-, 6- eller 7-leddet ring, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
7. Forbindelse med formel (I)
hvor R1, R2, R3, n, R6, R7, R8 og m har betydningerne ifølge krav 5, og R4 er valgt fra gruppen, der består af hydrogen, halogen, cyano, l-3C-alkyl, 3-6C-cycloalkyl, 2-3C-alkenyl, 1-3C- halogenalkyl, 1-3C-hydroxyalkyl, l-3C-alkoxy, 1-3C- halogenalkoxy, -C(0)-(l-3C-alkyl), COOH, (l-3C-alkylen)-C00H, -(l-3C-alkylen)-C00-(l-3C-alkyl), -C00-(l-4C-alkyl), -C(0)NH2, -C(0)NH(1-3C-alkyl), -C(0)N(1-3C-alkyl)2, -C(0)NH-(l-3C-alkyl)-OH, -C(0)-(N-heterocyclyl), -SO2-NH-(3-6C-cycloalkyl), -SO2-(N- heterocyclyl), hvilken gruppe eventuelt er substitueret en eller flere gange identisk eller forskelligt med en substituent valgt blandt: hydroxy, halogen, cyano, l-6C-alkyl, l-4C-halogenalkyl og 1-6C-alkoxy, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
8. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor, R1 er hydrogen.
9. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5, hvor, R2 og R3 er halogen, især fluor, chlor eller brom, fortrinsvis fluor eller chlor.
10. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor R4 uafhængigt er l-6C-alkyl, l-6C-hydroxyalkyl, l-6C-alkoxy, -O-(2-6C-alkylen)-O-C(O)-(l-6C-alkyl) , l-6C-halogenalkoxy eller 3-7C-cycloalkyl.
11. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor R4 uafhængigt er l-4C-alkyl, l-4C-hydroxyalkyl, l-4C-alkoxy, -O-(2-4C-alkylen)-O-C(O)-(l-4C-alkyl), l-4C-halogenalkoxy eller 3-7C-cycloalkyl.
12. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor R4 er valgt fra gruppen, der består af l-3C-alkyl, 3-6C-cycloalkyl, 1-3C-hydroxyalkyl, l-3C-alkoxy, 1-3C- halogenalkoxy.
13. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5, hvor n er 1.
14. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor R6 er (d) l-6C-alkoxy, der eventuelt er substitueret uafhængigt en eller flere gange med (dl) OH, (d5) NR10R41.
15. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor R6 er -0(1 — 3C —alkyl) , -0-(l-3C-halogenalkyl), -0-(l-3C-alkylen eventuelt substitueret med en hydroxygruppe)-OH eller -0(1-3C-alkylen eventuelt substitueret med en hydroxygruppe) -NR10R11, fortrinsvis l-3C-alkoxy, -0-(l-3C-alkylen)-OH, -0-(1-30-alkylen)-NH2, -0-(l-3C-alkylen)-NH(l-3C-alkyl) eller -0-(1-30- alkylen)-N(1-30-alkyl)2.
16. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5, hvor R7 er hydrogen.
17. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 4, hvor R8 er halogen, l-6C-alkyl eller l-6C-halogenalkyl.
18. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5, hvor R8 er fluor, l-3C-alkyl, l-3C-halogenalkyl.
19. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5, hvor m er 0, 1 eller 2.
20. Forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 5, hvor R10, R11 uafhængigt af hinanden er hydrogen, l-4C-alkyl eller sammen med nitrogenatomet, hvortil de er bundet, danner en 4-6-leddet heterocyklisk ring, der eventuelt indeholder ét yderligere heteroatom valgt fra gruppen, der består af 0 eller N, og eventuelt er substitueret med 1-2 halogenatomer, især fluoratomer.
21. Forbindelser med formel (I) ifølge et hvilket som helst af kravene 1 til 5, der er valgt fra gruppen, der består af: 2-[1-(6-chlor-2-fluor-3-methylbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(6-chlor-2-fluor-3-methoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-2-{1-[3-(5-methyl-l,2,4-oxadiazol-3-yl)benzyl]-1H-indazol-3-yl}-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2-chlor-4,5-dimethylbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-2-{1-[4 - (pentafluor-λ6-sulfanyl)benzyl]-lH-indazol-3-yl}-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2,6-difluor-3-methoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(2, 6-difluor-3-methoxybenzyl)-2-[1-(2,6-difluor-3-methoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-{1-[ (6-brom-l,3-benzodioxol-5-yl) methyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(4-ethoxy-2,6-difluorbenzyl)-2-[1-(4-ethoxy-2, 6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzonitril, 2-[1-(2-chlor-4-methoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2- [1-(3,4-dihydro-2H-l,5-benzodioxepin-6-ylmethyl)-lH-indazol- 3- yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2, 6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(2,6-difluorbenzyl)-2-[1-(2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-N-(pyridin-4-yl)-2-(1 — {3 — [(trifluormethyl)sulfanyl]benzyl}-lH-indazol-3-yl)pyrimidin-4-amin, 2-[1-(2,3-difluor-4-methylbenzyl)-lH-indazol-3-yl]-5-methoxy- N-(pyridin-4-yl)pyrimidin-4-amin, N-(2,3-difluor-4-methylbenzyl)-2-[1-(2,3-difluor-4-methylbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-2-{1-[4-(lH-pyrazol-l-yl)benzyl]-lH-indazol-3-yl}-N-(pyridin-4-yl)pyrimidin-4-amin 2-[1-(2,6-dichlorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(2,6-dichlorbenzyl)-2-[1-(2,6-dichlorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-N-(pyridin-4-yl)-2-(1 — {4 — [(trifluormethyl)sulfany1]benzyl}-lH-indazol-3-yl)pyrimidin-4-amin, 2-[1- (2-chlorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(2-chlorbenzyl)-2-[1-(2-chlorbenzyl)-lH-indazol-3-yl]-5- methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, methyl-3-chlor-4-({3-[5-methoxy-4-(pyridin-4- ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzoat, methyl-3-chlor-4-{ [ (2 — {1—[2-chlor-4-(methoxycarbonyl) benzyl]- lH-indazol-3-yl}-5-methoxypyrimidin-4-yl)(pyridin-4- yl)amino]methyl}benzoat, 2-[1-(4-brom-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2-chlor-4-fluor-3-methoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,3-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(4-ethoxy-2,3-difluorbenzyl)-2-[1-(4-ethoxy-2,3-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-N-(pyridin-4-yl)-2-{1-[2,3,5,6-tetrafluor-4 - (2,2,2-trifluorethoxy)benzyl]-lH-indazol-3-yl}pyrimidin-4-amin, 5-methoxy-N-(pyridin-4-yl)-N-[2,3,5,6-tetrafluor-4-(2,2,2-trifluorethoxy)benzyl]— 2 —{1—[2,3,5,6-tetrafluor-4 - (2,2,2-trifluorethoxy)benzyl]-lH-indazol-3-yl}pyrimidin-4-amin, methyl-2,4-dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzoat, 5-methoxy-N-(pyridin-4-yl)-2-[1-(2,4,6-trifluorbenzyl)-1H-indazol-3-yl]pyrimidin-4-amin, 5-methoxy-N-(pyridin-4-yl)-N-(2,4,6-trifluorbenzyl)-2-[1-(2,4, 6-trifluorbenzyl)-lH-indazol-3-yl]pyrimidin-4-amin, 2- [1- (2 — fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2,4-dichlorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2 — fluor-4-iodbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2-brombenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-(2-brombenzyl)-2-[1-(2-brombenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, [3-fluor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl] -lH-indazol-l-yl}methyl)phenyl]eddikesyre, 5-methoxy-N-(pyridin-4-yl)-2-[1-(2,3,5,6-tetrafluor-4-methoxybenzyl)-lH-indazol-3-yl]pyrimidin-4-amin, 5-methoxy-2-[1-(4-propylbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2 —{1—[2,6-dichlor-4-(trifluormethoxy)benzyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-[2,6-dichlor-4-(trifluormethoxy)benzyl]— 2 —{1—[2,6-dichlor-4-(trifluormethoxy)benzyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 7-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)-3,4-dihydroquinolin-2(IH)-on, 2-[1-(2-chlor-4-iodbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(3,5-dimethoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2 —{1—[2-chlor-6-(trifluormethyl)benzyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2- [1-(2-chlor-5-fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 7-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)-4-methyl-2H-chromen-2-on, 3- fluor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]- lH-indazol-l-yl}methyl)benzonitril, 4- {[{2-[1-(4-cyano-2-fluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}(pyridin-4-yl)amino]methyl}-3-fluorbenzonitril, 2 —{1—[2,6-dichlor-3-(trifluormethyl)benzyl]-lH-indazol-3-yl}- 5- methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, ethyl-[3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)phenyl]acetat, 2-[1- (4 — fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-cyclopropyl-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzensulfonamid, 6- ({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-1H-indazol-l-yljmethyl)-l-benzofuran-2(3H)-on, 2- {1-[4-(difluormethoxy)-2,6-difluorbenzyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, tert-butyl-3-chlor-4-({3-[5-methoxy-4-(pyridin-4- ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzoat, ethyl-2-[3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yljmethyl)phenyl]-2-methylpropanoat, 4- ({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzonitril, 5- methoxy-2-{1-[4-(morpholin-4-ylsulfonyl)benzyl]-lH-indazol- 3- yl}-N-(pyridin-4-yl)pyrimidin-4-amin, 2- [1-(2, 6-dichlor-3-nitrobenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 3- ({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzonitril, N-[4-(difluormethoxy)-2,6-difluorbenzyl]-2-{1-[4-(difluormethoxy)-2,6-difluorbenzyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 5-methoxy-N-(pyridin-4-yl)— 2 —{1—[3-(lH-pyrrol-l-yl)benzyl]-1H-indazol-3-yl}pyrimidin-4-amin, 3,5-difluor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzonitril, 5-methoxy-2-{1-[2-methoxy-4-(trifluormethyl)benzyl]-1H-indazol-3-yl}-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2,6-difluor-3-methylbenzyl)-lH-indazol-3-yl]-5-methoxy- N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2 — fluor-6-methoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 3,5-difluor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzamid, 2-[3,5-difluor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-1-yl}methyl)phenoxy]ethylacetat, 2-[1-(2,6-difluor-4-propoxybenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2-fluor-6-methoxybenzyl)-lH-indazol-3-yl] -5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-4-(pyridin- 4- ylamino)pyrimidin-5-ol, 2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol, 2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol, 2-[1-(4 — fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-ol, {3-[({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl] - 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)methyl]oxetan-3-yl}methanol, {3 - [ ({2-[1- (2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)methyl]oxetan-3-yl}methanol, (3-{[(2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-{[3-(hydroxymethyl)oxetan-3-yl]methoxy}pyrimidin-4-yl)(pyridin-4-yl) amino]methyl}oxetan-3-yl) methanol, 1- ({2-[1- (2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)methansulfonamid, 5- [2-(dimethylamino)ethoxy]-2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2- [1- (2 — fluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)-5-[2-(lH-tetrazol-5-yl)ethoxy]pyrimidin-4-amin, 2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)-5-[2-(lH-tetrazol-5-yl)ethoxy]-N-[2 - (lH-tetrazol-5-yl)ethyl]pyrimidin-4-amin, 5-[2-(dimethylamino)ethoxy]-2-[1-(4-fluorbenzyl)-lH-indazol-3- yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)-5-(1H-tetrazol-5-ylmethoxy)pyrimidin-4-amin, 5-[2-(dimethylamino)ethoxy]-2-[1-(4-ethoxy-2,6-difluorbenzyl) -lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 1- ({2 - [1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)-3-(piperidin-1-yl)propan-2-ol, 2- [1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-(2-methoxyethoxy)-N-(pyridin-4-yl)pyrimidin-4-amin, tert-butyl-2-[ ({2-[1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol- 3- yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)methyl]morpholin-4-carboxylat, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-[2-(morpholin-4-yl)ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amin, 2- [1- (2-fluorbenzyl)-lH-indazol-3-yl]-5-{ [3-(methoxymethyl) - 1,2,4-oxadiazol-5-yl]methoxy]-N-(pyridin-4-yl)pyrimidin-4-amin, ethyl-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl] - 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)acetat, 1- (3,3-difluorazetidin-l-yl)-2-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethanon, 2- [1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-[2-(methylsulfanyl) ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amin, 2 - [2 - ({2 - [1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl] - 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethoxy]ethanol, myresyre-(5 S)-5-[ ({2-[1-(4-ethoxy-2,6-difluorbenzyl)-1H-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)methyl]pyrrolidin-2-on (1:1), (5R)-5-[ ({2-[1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]- 4- (pyridin-4-ylamino)pyrimidin-5-yl}oxy)methyl]pyrrolidin-2-on, tert-butyl-{2-[2-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl] - 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethoxy]ethyl}carbamat, 2 - ({2 - [1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)-1-(3 — fluorazetidin-1-yl)ethanon, (5 S)-5-[ ({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]- 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)methyl]-pyrrolidin-2-on, tert-butyl-[2-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol- 3- yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethyl]carbamat, N-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-8-(pyridin-4-yl)-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-7-yl}methyl)formamid, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-N-(pyridin- 4- yl)pyrimidin-4-amin, 2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-cyclopropyl-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2-(1 — {2,6-difluor-4- [ (IE)-prop-l-en-l-yl]benzyl}-lH-indazol-3-yl)-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 1- [3,5-difluor-4-({3-[5-methoxy-4-(pyridin-4- ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)phenyl]ethanon, [2,4-dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin- 2- yl]-lH-indazol-l-yl}methyl)phenyl]methanol, 2-[3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-1Η-indazol-l-yl}methyl)phenyl]ethanol, 2-[3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-1Η-indazol-l-yl}methyl)phenyl]-2-methylpropan-l-ol, [4-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-ylJamino)pyridin-3-yl]methanol, 2-[3-chlor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)phenyl]propan-2-ol, 1- [3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-1Η-indazol-l-yl}methyl)phenyl]-2-methylpropan-2-ol, 2- [2,4-dichlor-3-({3-[5-methoxy-4-(pyridin-4- ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)phenyl]propan-2-ol, 5- (difluormethoxy)-2-[1-(4-ethoxy-2,6-difluorbenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 5-(difluormethoxy)-N-(difluormethyl)-2-[1-(4-ethoxy-2,6- difluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 4-[(difluormethyl)(pyridin-4-yl)amino]-2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]pyrimidin-5-ol, 2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)-5-(2,2,2-trifluorethoxy)pyrimidin-4-amin, 2- [1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)-5-(2,2,2-trifluorethoxy)pyrimidin-4-amin, 3- ({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)propan-l,2-diol, (2S)-3 - ({2 - [1- (2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)propan-l,2-diol, (2R)—3—({2—[1—(2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)propan-l,2-diol, 2 - ({2 - [1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl] - 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethanol, 2-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethanol, ethyl-4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-(2-hydroxyethoxy)pyrimidin-4-yl}amino)pyridin-3-carboxylat, 4 - ({2 - [ 1- (2-fluorbenzyl)-lH-indazol-3-yl]-5-(2-hydroxyethoxy)pyrimidin-4-yl}amino)-N-methylpyridin-3-carboxamid, 4- ({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-(2-hydroxyethoxy)pyrimidin-4-yl}amino)pyridin-3-carboxamid, 2-hydroxyethyl-4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-(2-hydroxyethoxy)pyrimidin-4-yl}amino)pyridin-3-carboxylat, 5- (cyclopropyloxy)-2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-aminhydrochlorid (1:1) , (2 S)-3-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)propan-l,2-diolhydrochlorid (1:1), 2 - ({2 - [1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)ethanolhydrochlorid (1:1) , 2-[1-(2, 6-dichlorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-aminhydrochlorid (1:1), [2,4-dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)phenyl]methanolhydrochlorid (1:1) , (2R)—3—({2—[1—(2 — fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)propan-l,2-diolhydrochlorid (1:1) , N-{2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl}-N-(pyridin-4-yl)acetamid, N-{2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl}-2-methoxy-N-(pyridin-4-yl)acetamid, N-{2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3- yl]pyrimidin-4-yl}-N-(pyridin-4-yl)tetrahydro-2H-pyran-4- carboxamid, N-{2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl}-2-(2-methoxyethoxy)-N-(pyridin-4-yl)acetamid, 2-[{2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl} (pyridin-4-yl) amino]ethanol, (3-{[{2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl} (pyridin-4-yl) amino]methyl}oxetan-3-yl) methanol, 2-{1-[4-brom-2-fluor-6-(2,2,2-trifluorethoxy)benzyl]-lH-indazol-3-yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2- {1-[4-brom-2,6-bis(2,2,2-trifluorethoxy)benzyl]-lH-indazol- 3- yl}-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 2.4- dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzoesyre, ({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl] - 4-(pyridin-4-ylamino)pyrimidin-5-yl}oxy)eddikesyre, 2.4- dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yljmethyl)-N-methylbenzamid, 2.4- dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzamid, 2.4- dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yljmethyl)-N,N-dimethylbenzamid, 2.4- dichlor-N-(2-hydroxyethyl)-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)benzamid, [2,4-dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yljmethyl)phenyl](morpholin-4-yl)methanon, 3,5-difluor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yljmethyl)-N-methylbenzamid, 2-[1-(4-ethynyl-2-fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, {2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-8-(pyridin-4-yl)-7,8-dihydro-6H-pyrimido[5,4-b][1,4]oxazin-7-yl}methanol, 2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-methyl-N-(pyridin-4-yl)pyrimidin-4-amin, 4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-3-carbonitril, 2-[1- (2 — fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N,N-di(pyridin-4-yl)pyrimidin-4-amin, methyl-4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-3-carboxylat, 2-[1- (2 — fluorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, 4-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-3-carbonitril, 2-[ (3 —{4 —[ (2,6-dimethylpyridin-4-yl)amino]-5-methoxypyrimidin-2-yl}-lH-indazol-l-yl) methyl]-5-ethoxy-3-fluorphenol, 4-({5-methoxy-2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]pyrimidin-4-yl}amino)pyridin-2(IH)-on, 4-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-2(IH)-on, 4-({5-methoxy-2-[1-(4-propylbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl}amino)nicotinonitril, 4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-3-carboxamid, 4-({5-methoxy-2-[1-(4-propylbenzyl)-lH-indazol-3-yl]pyrimidin-4-yl}amino)pyridin-3-carboxamid, 4 - ({2 - [1- (4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-3-carboxamid, 4—({2—[1—(2, 6-difluor-4-hydroxybenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-yl}amino)pyridin-3-carboxamid, 4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-hydroxypyrimidin-4-yl}amino)pyridin-3-carbonitril, 4-({4-[(3-cyanopyridin-4-yl)amino]-2-[1-(2-fluorbenzyl)-1H-indazol-3-yl]pyrimidin-5-yl}oxy)pyridin-3-carbonitril, 5-methoxy-2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]-N-[3-(trifluormethyl)pyridin-4-yl]pyrimidin-4-amin, 3-chlor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]- lH-indazol-l-yl}methyl)benzoesyre, myresyre-3-chlor-4-({3-[5-methoxy-4-(pyridin-4- ylamino)pyrimidin-2-yl]-lH-indazol-l-yljmethyl)-N- methylbenzamid (1:1), 3- chlor-4-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-l-yl}methyl)-N-methylbenzamid, 4- ({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-hydroxypyrimidin- 4-yl}amino)pyridin-3-carboxamid, 4-({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5-hydroxypyrimidin-4-yl}amino)pyridin-3-carboxylsyre, ethyl-4-({2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-5-hydroxypyrimidin-4-yl}amino)pyridin-3-carboxylat, 2- [1- (2 — fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-carbonitril, 2-[1-(2 — fluorbenzyl)-lH-indazol-3-yl]-4-(pyridin-4-ylamino)pyrimidin-5-carboxamid, 4- ({2-[1-(2-fluorbenzyl)-lH-indazol-3-yl]-5 - (2-hydroxyethoxy)pyrimidin-4-yl}amino)pyridin-3-carboxylsyrehydrochlorid (1:1), N-(2-fluorpyridin-4-yl)-5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amin, N-(2,6-difluorpyridin-4-yl)-5-methoxy-2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]pyrimidin-4-amin, N-(3-fluorpyridin-4-yl)-5-methoxy-2-[1-(4-methoxybenzyl)-1H-indazol-3-yl]pyrimidin-4-amin, 5- methoxy-2-[1-(4-methoxybenzyl)-lH-indazol-3-yl]-N-(2-methylpyridin-4-yl)pyrimidin-4-amin, N-(difluormethyl)-2-[1-(4-ethoxy-2,6-difluorbenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-[2-(methylsulfinyl) ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-[2-(methylsulfinyl) ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amin (enantiomer 1), 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl] -5-[2- (methylsulfinyl) ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amin (enantiomer 2), 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-[2-(methylsulfonyl) ethoxy]-N-(pyridin-4-yl)pyrimidin-4-amin, 5-(2-aminoethoxy)-2-[1-(4-ethoxy-2,6-difluorbenzyl)-1H-indazol-3-yl]-N-(pyridin-4-yl)pyrimidin-4-amin, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-(morpholin-2-ylmethoxy)-N-(pyridin-4-yl)pyrimidin-4-amin, ethyl-4-({2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]- 5-methoxypyrimidin-4-yl}amino)pyridin-3-carboxylat, N-(3,5-difluorpyridin-4-yl)-2-[1-(4-ethoxy-2,6-difluorbenzyl)-lH-indazol-3-yl]-5-methoxypyrimidin-4-amin, 2-[1-(3-amino-2,6-dichlorbenzyl)-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, N-[2,4-dichlor-3-({3-[5-methoxy-4-(pyridin-4-ylamino)pyrimidin-2-yl]-lH-indazol-1-yl}methyl)phenyl]acetamid, 2-[1-(4-ethoxy-2,6-difluorbenzyl)-4-methyl-lH-indazol-3-yl]-5-methoxy-N-(pyridin-4-yl)pyrimidin-4-amin, eller en N-oxid, et salt, en tautomer eller en stereoisomer af forbindelsen eller et salt af N-oxiden, tautomeren eller stereoisomeren.
22. Fremgangsmåde til fremstilling af forbindelser med generel formel (I) ifølge kravene 1 til 21, hvor R7 er hydrogen som afspejlet i formel (la), der er kendetegnet ved, at en forbindelse med formel (1-4)
hvor R1, R2, R3, R4, R6 og n har betydningen ifølge et hvilket som helst af kravene 1 til 21, reageres med en forbindelse med formel (C)
hvor R8 og m har betydningen ifølge et hvilket som helst af kravene 1 til 20, og X' er F, Cl, Br, I, boronsyre eller en boronsyreester, i nærvær af en egnet base og en egnet palladiumkatalysator, eventuelt i nærvær af en egnet ligand til frembrinaelse af en forbindelse med formel (la)
der eventuelt efterfølgende afbeskyttes til frembringelse af en forbindelse med generel formel (I), hvor R7 er hydrogen, og R1, R2, R3, R4, R6, R8 og n og m har betydningen ifølge et hvilket som helst af kravene 1 til 21.
23. Fremgangsmåde til fremstilling af forbindelser med generel formel (I) ifølge kravene 1 til 21, hvor en forbindelse med formel (Ib)
hvor R1, R2, R3, R6, R7, R8 og m har betydningen ifølge et hvilket som helst af kravene 1 til 20, og R' er l-6C-alkyl eller benzyl, behandles med et egnet syresystem til spaltning af benzylgruppen til opnåelse af en forbindelse med formel 1-5
efterfulgt af reaktion af forbindelsen med formel 1-5 med en forbindelse med generel formel (B)
hvor R2, R3, R4 og n har betydningen ifølge et hvilket som helst af kravene 1 til 21, og X er Cl, Br, I, en arylsulfonat, såsom p-toluensulfonat, eller en alkylsulfonat, såsom methansulfonat eller en trifluormethansulfonatgruppe, i et egnet opløsningsmiddelsystem i nærvær af en egnet base i et temperaturinterval fra stuetemperatur til kogepunktet for det respektive opløsningsmiddel til tilvejebringelse af forbindelser med generel formel (I).
24. Mellemforbindelse med generel formel (1-5) ifølge krav 2 3
hvor R1, R6, R7 R8 og m har betydningen ifølge et hvilket som helst af kravene 1 til 21.
25. Anvendelse af en forbindelse med formel 1-5 ifølge krav 24 til fremstilling af en forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 21.
26. Forbindelse med generel formel (I) ifølge et hvilket som helst af kravene 1 til 21 til anvendelse til behandling eller profylakse af sygdomme.
27. Forbindelse med generel formel (I) ifølge krav 26, hvor sygdommene er hyperproliferative sygdomme og/eller forstyrrelser, der responderer på induktion af apoptose.
28. Forbindelse med generel formel (I) ifølge krav 27, hvor de hyperproliferative sygdomme og/eller forstyrrelser, der responderer på induktion af apoptose, er hæmotologiske tumorer, faste tumorer og/eller metastaser deraf.
29. Forbindelse med formel (I) ifølge krav 28, hvor tumorerne er cervix-, bryst-, ikke-småcellet lunge-, prostata-, colon-eller melanomtumorer og/eller metastaser deraf.
30. Farmaceutisk sammensætning, der omfatter mindst én forbindelse med generel formel (I) ifølge et hvilket som helst af kravene 1 til 21 sammen med mindst ét farmaceutisk acceptabelt hjælpestof.
31. Sammensætning ifølge krav 30 til behandling af hæmotologiske tumorer, faste tumorer og/eller metastaser deraf.
32. Kombination, der omfatter en eller flere første aktive bestanddele valgt blandt en forbindelse med generel formel (I) ifølge et hvilket som helst af kravene 1 til 21 og en eller flere anden aktive bestanddele valgt blandt kemoterapeutiske anticancermidler og målspecifikke anticancermidler.
33. Mellemforbindelse med generel formel (1-4)
hvor R1, R2, R3, R4, R6 og n har betydningen ifølge krav 9.
34. Anvendelse af en forbindelse med formel 1-4
hvor R1, R2, R3, R4, R6 og n har betydningen ifølge et hvilket som helst af kravene 1 til 21, til fremstilling af en forbindelse med formel (I) ifølge et hvilket som helst af kravene 1 til 21.
DK12766997.6T 2011-10-06 2012-10-04 Substituerede benzylindazoler til anvendelse som bub1-kinasehæmmere til behandling af hyperproliferative sygdomme DK2763982T3 (da)

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