DK2809670T3 - 1h-pyrrolo[2,3-b]pyridin-derivater og deres anvendelse som kinaseinhibitorer - Google Patents

1h-pyrrolo[2,3-b]pyridin-derivater og deres anvendelse som kinaseinhibitorer Download PDF

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DK2809670T3
DK2809670T3 DK13703121.7T DK13703121T DK2809670T3 DK 2809670 T3 DK2809670 T3 DK 2809670T3 DK 13703121 T DK13703121 T DK 13703121T DK 2809670 T3 DK2809670 T3 DK 2809670T3
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pyrrolo
pyrazole
pyridin
amide
carboxylic acid
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Stephen Stokes
Christoper John Graham
Stuart Christopher Ray
Emma Jayne Stefaniak
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Vernalis R&D Ltd
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Claims (15)

1. Forbindelse af formel I:
(I) eller et farmaceutisk acceptabelt salt deraf, hvor: hvert Z er uafhængigt (Alk)n-Rn-(Alk)n-X, hvor hvert Alk er uafhængigt (Ci til C12) alkylen eller (C2 til C12) alkenylen, hver af hvilke kan eventuelt substitueres; hvert n er uafhængigt 0 eller 1; hvert R er uafhængigt eventuelt substitueret arylen eller heteroarylen, eller eventuelt substitueret cykloalkylen eller heterocykel, -O-, -S-, -(C=0)-, - (OS)-, -SO2-, -C( = 0)0-, -C(=0)NRA-, -C(=S)NRA-, -S02NRA-, -NRAC(=0)-, -NRaS02- eller -NRA- hvor RA er hydrogen, C1-C6 alkyl, -Ci-Ce alkyl(cykloalkyl), Ci-Ce alkyl(Ci-Ce alkoxy) eller CiCe alkoxy; hvert X er uafhængigt halogen, -H, -ORA, NRARA, eventuelt substitueret aryl eller heteroaryl, eller eventuelt substitueret cykloalkyl eller heterocykel, CN eller C(halogen)aHb, hvor a er 1, 2, eller 3, og b er (3-a); Y er eventuelt substitueret aryl eller heteroaryl, eller eventuelt substitueret cykloalkyl eller heterocykel; og R1 er H eller C1-C6 alkyl, med det forbehold at forbindelsen ikke er N-(5-brom-4-fluor-lH-pyrrolo[2,3-b]pyridin-3-yl)-l-(4-methoxybenzyl)-lH-pyrazol-4-carboxamid eller (R)-tert-butyl l-(5-brom-3-(l-(4-methoxybenzyl)-lHpyrazol-4-carboxamido)-lH-pyrrolo[2,3-b]pyridin-4-yl)piperidin-3-ylcarbamat.
2. Forbindelse ifølge krav 1, hvor de eventuelle substituenter for gruppen Y er valgt fra (Ci-Ce)alkyl, hydroxy, hydroxy(Ci-C6)alkyl, mercapto, mercapto(Ci-C6)alkyl, (Ci-C6)alkylthio, halo, trifluormethyl, trifluormethoxy, nitro, nitril (-CN), oxo, phenyl, -COOH, -COORA, -CORa, -S02Ra, -CONHz, -SO2NH2, -CONHRA, -so2nhra, -conrarb, -so2nrarb, -nh2, -nhra, -nrarb, -oconh2, -oconhra, - OCONRARB, -NHCORA, -NHbCOORa, -NRbCOORa, -NHS020Ra, -NRbS020Ra, -NHC0NH2, -NRaCONH2, -NHCONHR6, -NRaCONHR, -NHCONRaRb eller -NRACONRARB hvor RA og RB er uafhængigt en (CiC6)alkylgruppe, eller RA og RB når forbundet til det samme nitrogen kan danne en cyklisk amino-ring valgt fra en morpholinyl-, piperidinyl- eller piperazinyl-ring.
3. Forbindelse ifølge krav 1 eller krav 2, hvor RA er hydrogen eller C1-C6 alkyl.
4. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor mindst et Z er H, halogen, eventuelt substitueret aryl, eventuelt substitueret heteroaryl, eventuelt substitueret nitrogen-indeholdende heterocykel, Ci til C6 alkyl eller 0RA.
5. Forbindelse ifølge et hvilket som helst af kravene 1 til 3, hvor mindst et Z er (Alk)n-eventuelt substitueret arylen-(Alk)n-eventuelt substitueret heterocykel.
6. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor Ri er H og hvor Y er phenyl.
7. Forbindelse ifølge et hvilket som helst af de foregående krav, hvilken har formlen la:
eller et farmaceutisk acceptabelt salt deraf, hvor: Zi og Z2 er uafhængigt (Alk)n-Rn-(Alk)n-X; og Alk, n, R, X, Y, RA og R1 er som defineret i krav 1.
8. Forbindelse ifølge krav 7, hvor Zi er halogen, phenyl, ORA eller Ci til Ce alkyl, og Z2 er eventuelt substitueret aryl eller eventuelt substitueret heterocykel, eller hvor Z2 er halogen, CF3, cyklopropyl, phenyl, ORA eller Ci til C6 alkyl, og Zi er eventuelt substitueret aryl eller eventuelt substitueret heterocykel.
9. Forbindelse ifølge et hvilket som helst af de foregående krav, hvor heterocyklen eller den nitrogen-indeholdende heterocykel er en eventuelt substitueret piperidin, piperazin eller morpholin.
10. Forbindelse ifølge et hvilket som helst af de foregående krav, hvilken er en af forbindelserne anført nedenfor, eller et farmaceutisk acceptabelt salt deraf: l-Benzyl-lH-pyrazol-4-carboxylsyre (5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid; l-Benzyl-lH-pyrazol-4-carboxylsyre (lH-pyrrolo[2,3-b]pyridin-3-yl)-amid; l-Benzyl-lH-pyrazol-4-carboxylsyre (4-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid; l-Benzyl-lH-pyrazol-4-carboxylsyre (5-phenyl-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid; eller l-Benzyl-lH-pyrazol-4-carboxylsyre (5-piperidin-l-yl-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid. N-{4-[(3R)-3-Aminopiperidin-l-yl]-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl>- l-benzyl-lH-pyrazol-4-carboxamid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-pyrrolidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-brom-4-((R)-3-methylamino-piperidin-l-yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-brom-4-((R)-3-ethylamino-piperidin-l-yl)-lH-pyrrolo[2(3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-brom-4-((R)-3-hydroxy-pyrrolidin-l-yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-brom-4-((R)-3-hydroxy-piperidin-l-yl)-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-brom-4-(3-dimethylamino-piperidin-l-yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-brom-4-[(R)-3-(cyclopentylmethyl-amino)-piperidin-l-yl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-brom-4-((R)-3-isobutylamino-piperidin-l-yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-brom-4-[(R)-3-(2,2-dimethyl-propylamino)-piperidin-l-yl]-lH-pyrrolo[2,3-b]pyridin-3-yl}-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-brom-4-[(R)-3-(cyclopropylmethyl-amino)-pipendin-l-yl]-lH-pyrrolo[2,3-b]pyridin-3-yl}-amid l-(4-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Chlor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Methyl-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Methoxy-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-2-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-3-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-4-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid N-{4-[(3R)-3-aminopiperidin-l-yl]-5-chlor-lH-pyrrolo[2,3-b]pyridin-3-yl}- l-benzyl-lH-pyrazol-4-carboxamid l-(4-Methyl-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Chlor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Methoxy-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-pyrrolidin-l-yl)-5-chlor-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid N-{4-[(3R)-3-aminopiperidin-l-yl]-5-cyklopropyl-lH-pyrrolo[2,3-b]pyridin- 3-yl>-l-benzyl-lH-pyrazol-4-carboxamid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-hydroxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methyl-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(4-piperidin-l-ylmethyl-phenyl)-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid
1-Benzyl-lH-pyrazol-4-carboxylsyre [5-(4-{[(2-methoxy-ethyl)-methyl-amino]-methyl>-phenyl)-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(4-pyrrolidin-l-ylmethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[4-(4-fluor-piperidin-l-ylmethyl)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(4-dimethylaminomethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[4-(3-fluor-piperidin-l-ylmethyl)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(4-methylaminomethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(4-morpholin-4-ylmethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[4-(3,3-difluor-pyrrolidin-l-ylmethyl)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(3-dimethylaminomethyl-phenyl)-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(3-fluor-piperidin-l-ylmethyl)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(3,3-difluor-piperidin-l-ylmethyl)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(3-azetidin-l-ylmethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(3,3-difluor-azetidin-l-ylmethyl)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid
1- Benzyl-lH-pyrazol-4-carboxylsyre [5-(5-pyrrolidin-l-ylmethyl-thiophen- 2- yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(5-pyrrolidin-l-ylmethyl-thiophen- 3- yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[5-(3,3-difluor-azetidin-l-ylmethyl)-thiophen-3-yl]-lH-pyrrolo[2,3-b]pyridin-3-yl}-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(3-pyrrolidin-l-ylmethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-fluor-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-phenyl-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-cyano-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(2-morpholin-4-yl-ethoxy)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl}-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(3-dimethylamino-2,2-dimethyl-propoxy)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl}-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(3-morpholin-4-yl-propoxy)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(l-methyl-piperidin-3-ylmethoxy)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(oxetan-3-yloxy)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[3-(2-pyrrolidin-l-yl-ethoxy)-phenyl]-lH-pyrrolo[2,3-b]pyridin-3-yl>-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [4-((3R,4R)-3-amino-4-cyklopropyl-piperidin-l-yl)-5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(2-fluor-4-pyrrolidin-l-ylmethyl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(3-pyrrolidin-l-yl-phenyl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre [5-(l-methyl-lH-pyrazol-4-yl)-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Benzyl-lH-pyrazol-4-carboxylsyre (5-pyridin-4-yl-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-Benzyl-lH-pyrazol-4-carboxylsyre (5-pyridin-3-yl-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(3-Methoxy-benzyl)-lH-pyrazol-4-carboxylsyre (5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(2-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre (5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(2-Cyano-benzyl)-lH-pyrazol-4-carboxylsyre (5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(lH-Pyrrol-2-ylmethyl)-lH-pyrazol-4-carboxylsyre (5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(4-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre (5-brom-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-Benzyl-lH-pyrazol-4-carboxylsyre (5-methyl-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-Benzyl-lH-pyrazol-4-carboxylsyre (5-chlor-lH-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(4-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre (5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl)-amid l-(3-Methoxy-benzyl)-lH-pyrazol-4-carboxylsyre (5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl)-amid
1-Benzyl-l H-pyrazol-4-carboxylsyre {5-[3-((S)-l-methyl-pyrrolidin-2-ylmethoxy)-phenyl]-l H-pyrrolo[2,3-b]pyridin-3-yl}-amid
1-Benzyl-l H-pyrazol-4-carboxylsyre {5-[3-(l-methyl-piperidin-3-yloxy)-phenyl]-l H-pyrrolo[2,3-b]pyridin-3-yl}-amid
1-Benzyl-l H-pyrazol-4-carboxylsyre {5-[4-(3-dimethylamino-propoxy)-phenyl]-l H-pyrrolo[2,3-b]pyridin-3-yl}-amid l-Benzyl-lH-pyrazol-4-carboxylsyre {5-[l-(2-diethylamino-ethyl)-lH-pyrazol-4-yl]-l H-pyrrolo[2,3-b]pyridin-3-yl}-amid
1-Benzyl-l H-pyrazol-4-carboxylsyre {5-[l-(2-pyrrolidin-l-yl-ethyl)-lH-pyrazol-4-yl]-lH-pyrrolo[2,3-b]pyridin-3-yl}-amid l-Pyridin-4-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-3-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-2-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-3-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-4-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-2-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-chlor-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-4-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methyl-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-3-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methyl-l H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(3-Methyl-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(3-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(2-Chlor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(2-Methyl-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-methoxy-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-(4-Fluor-benzyl)-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-trifluormethyl-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid
1-Benzyl-l H-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-trifluormethyl-1 H-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-3-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-trifluormethyl-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid l-Pyridin-2-ylmethyl-lH-pyrazol-4-carboxylsyre [4-((R)-3-amino-piperidin-l-yl)-5-trifluormethyl-lH-pyrrolo[2,3-b]pyridin-3-yl]-amid
11. Farmaceutisk sammensætning omfattende en forbindelse af formel I:
(l) eller et farmaceutisk acceptabelt salt deraf, hvor: hvert Z er uafhængigt (Alk)n-Rn-(Alk)n-X, hvor hvert Alk er uafhængigt (Ci til C12) alkylen eller (C2 til C12) alkenylen, hver af hvilke kan eventuelt substitueres; hvert n er uafhængigt 0 eller 1; hvert R er uafhængigt eventuelt substitueret arylen eller heteroarylen, eller eventuelt substitueret cykloalkylen eller heterocykel, -O-, -S-, -(C=0)-, - (C=S)-, -SO2-, -C( = 0)0-, -C(=0)NRA-, -C(=S)NRA-, -S02NRA-, -NRAC(=0)-, -NRAS02- eller -NRA- hvor RA er hydrogen, C1-C6 alkyl, -C1-C6 alkyl(cykloalkyl), C1-C6 alkyl(Ci-Ce alkoxy) eller Ci-Ce alkoxy; hvert X er uafhængigt halogen, -H, -ORA, NRARA, eventuelt substitueret aryl eller heteroaryl, eller eventuelt substitueret cykloalkyl eller heterocykel, CN eller C(halogen)aHb, hvor a er 1, 2, eller 3, og b er (3-a); Y er eventuelt substitueret aryl eller heteroaryl, eller eventuelt substitueret cykloalkyl eller heterocykel; og R1 er H eller C1-C6 alkyl, og en eller flere farmaceutisk acceptable bærere og/eller excipienser.
12. Farmaceutisk sammensætning ifølge krav 11, hvor forbindelsen haret hvilket som helst yderligere kendetegn ifølge et hvilket som helst af kravene 2 til 10.
13. Forbindelse eller sammensætning ifølge et hvilket som helst af de foregående krav, til anvendelse i terapi.
14. Forbindelse til anvendelse ifølge krav 13, til behandlingen afen tilstand, der reagerer på inhibering af proteinkinase-aktivitet, hvor proteinkinasen er CHK1, og hvor tilstanden er valgt fra cancer og autoimmune lidelser.
15. Forbindelse til anvendelse ifølge krav 13, til behandlingen af cancer ved administration i kombination med radioterapi eller kemoterapi.
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