DK2061765T3 - Serin-threonin-proteinkinase- og parp-modulatorer - Google Patents

Serin-threonin-proteinkinase- og parp-modulatorer Download PDF

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DK2061765T3
DK2061765T3 DK07841767.2T DK07841767T DK2061765T3 DK 2061765 T3 DK2061765 T3 DK 2061765T3 DK 07841767 T DK07841767 T DK 07841767T DK 2061765 T3 DK2061765 T3 DK 2061765T3
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compound
alkyl
group
optionally substituted
protein
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DK07841767.2T
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Peter C Chua
Fabrice Pierre
Jeffrey P Whitten
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Senhwa Biosciences Inc
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Claims (14)

1. Forbindelse med en struktur med formlerne XIII, XIV, XV eller XVI:
Formel XIII Formel XIV
Formel XV Formel XVI eller et farmaceutisk acceptabelt salt deraf; hvor: Z5 er N eller CR6A; hver R6A, R6b, R6d og R8 uafhængigt er H eller en eventuelt substitueret C1-C8 alkyl-, C3-C8 cycloalkyl-, C2-C8 heteroalkyl-, C3-C8 heterocycloalkyl-, C2-C8 alkenyl-, C3-C8 cycloalkenyl-, C2-C8 heteroalkenyl-, C3-C8 heterocycloalkenyl-, C2-C8 alkynyl-, C2-C8 heteroalkynyl-, C1-C8 acyl-, C6-C10 aryl-, C5-C12 heteroaryl-, C7-C12 arylalkyl- eller C6-C12 heteroarylalkylgruppe, eller hver R6A, R6B, R6D og R8 uafhængigt er halo, CF3, OR, NR2, NROR, NRNR2, SR, SOR, S02R, S02NR2, NRS02R, NRCONR2, NRCOOR, NRCOR, CN, COOR, carboxy-bioisoster, CONR2, OOCR, COR, eller N02, R9 er uafhængigt en eventuelt substitueret C1-C8 alkyl-, C3-C8 cycloalkyl-, C2-C8 heteroalkyl-, C3-C8 heterocycloalkyl-, C2-C8 alkenyl-, C3-C8 cycloalkenyl-, C2-C8 heteroalkenyl-, C3-C8 heterocycloalkenyl-, C2-C8 alkynyl-, C2-C8 heteroalkynyl-, C1-C8 acyl-, C6-C10 aryl-, C5-C12 heteroaryl-, C7-C12 arylalkyl- eller C6-C12 heteroarylalkylgruppe, eller R9 er uafhængigt halo, OR, NR2, NROR, NRNR2, SR, SOR, S02R, S02NR2, NRS02R, NRCONR2, NRCOOR, NRCOR, CN, COOR, CONR2, OOCR, COR eller N02, hvor hver R uafhængigt er H eller C1-C8 alkyl, C3-C8 cycloalkyl, C2-C8 heteroalkyl, C3-C8 heterocycloalkyl, C2-C8 alkenyl, C3-C8 cycloalkenyl, C2-C8 heteroalkenyl, C3-C8 heterocycloalkenyl, C2-C8 alkynyl, C2-C8 heteroalkynyl, C1-C8 acyl, C6-C10 aryl, C5-C10 heteroaryl, C7-C12 arylalkyl eller C6-C12 heteroarylalkyl, og hvor to R det samme atom eller på tilstødende atomer kan forbindes for at danne en 3-8-leddet ring, der eventuelt indeholder én eller flere N, O eller S; og hver R-gruppe, og hver ring dannet med forbindelse af to R-grupper med hinanden eventuelt er substitueret med én eller flere substituenter udvalgt blandt halo, = O, =N-CN, =N-OR', =NR', OR’, NR'2, SR', S02R', S02NR'2, NR’S02R', NR'CONR'2, NR'COOR', NR'COR', CN, COOR', CONR'2, OOCR', COR' og N02, hvor hver R’ uafhængigt er H, C1-C6 alkyl, C3-C6 cycloalkyl, C2-C6 heteroalkyl, C3-C6 heterocycloalkyl, C1-C6 acyl, C6-C10 aryl, C5-C10 heteroaryl, C7-12 arylalkyl, eller C6-12 heteroarylalkyl, der hver eventuelt er substitueret med én eller flere grupper udvalgt blandt halo, C1-C4 alkyl, C3-C4 cycloalkyl, C1-C4 heteroalkyl, C3-C4 heterocycloalkyl, C1-C6 acyl, hydroxy, amino og =0; og hvor to R' kan forbindes for at danne en 3-7-leddet ring, der eventuelt indeholder op til tre heteroatomer udvalgt blandt N, O og S; n er O til 4; og p er O til 4; og ovennævnte eventuelle substituent er udvalgt fra gruppen bestående af halo, =0, =N-CN, N-OR, =NR, OR, NR2, SR, S02R, S02NR2, NRS02R, NRCONR2, NRCOOR, NRCOR, CN, CECR, COOR, CONR2, OOCR, COR og N02, hvor hver R uafhængigt er H, C1-C8 alkyl, C3-C8 cycloalkyl, C2-C8 heteroalkyl, C3-C8 heterocycloalkyl, C1-C8 acyl, C2-C8 alkenyl, C3-C8 cycloalkenyl, C2-C8 heteroalkenyl, C3-C8 heterocycloalkenyl, C2-C8 alkynyl, C2-C8 heteroalkynyl, C6-C10 aryl, eller C5-C10 heteroaryl, og hver R eventuelt er substitueret med halo, = O, =N-CN, N-OR’, =NR', OR’, NR’2, SR’, S02R’, S02NR’2, NR’S02R’, NR'CONR’2, NR'COOR', NR'COR', CN, OCR', COOR’, CONR’2, OOCR’, COR’ og N02, hvor hver R' uafhængigt er H, C1-C8 alkyl, C3-C8 cycloalkyl, C2-C8 heteroalkyl, C3-C8 heterocycloalkyl, C1-C8 acyl, C6-C10 aryl eller C5-C10 heteroaryl; og hvor en heteroalkylgruppe er en alkylgruppe med 1-3 O, S eller N heteroatomer eller kombinationer deraf i hovedkæderesten, en heteroalkenylgruppe er en alkenylgruppe med 1-3 O, S eller N heteroatomer eller kombinationer deraf i hovedkæderesten og en heteroalkynylgruppe er en alkynylgruppe med 1-3 O, S eller N heteroatomer eller kombinationer deraf i hovedkæderesten.
2. Forbindelse ifølge krav 1, hvor Z5 er N.
3. Forbindelse ifølge krav 1, hvor R8 er et carboxylat eller en carboxylsyre.
4. Forbindelse ifølge krav 1, hvor R9 er udvalgt blandt -C=CR, -C=CH, -CH3,-CH2CH3, -CF3, -C=N, -OR og halogen.
5. Forbindelse ifølge krav 4, hvor R9 er udvalgt blandt halogen eller -C^CH.
6. Forbindelse ifølge krav 5, der har følgende struktur
7. Forbindelse ifølge krav 5, der har følgende struktur
8. Forbindelse ifølge krav 5, hvor p er en eller to.
9. Forbindelse ifølge krav 5, hvor n er en eller to.
10. Forbindelse med formlen XIII, XIV, XV eller XVI, som defineret i et hvilket som helst af de foregående krav, til anvendelse i behandling af en tilstand relateret til afvigende celledeling, hvor celledelingstilstanden er udvalgt blandt en tumorassocieret cancer, en ikke-tumorassocieret cancer og maculadegeneration.
11. Forbindelse til anvendelse ifølge krav 10, hvor canceren er bryst-, prostata-, pancreas-, lunge, colorektal, hud- eller ovariecancer.
12. Forbindelse til anvendelse ifølge krav 10, hvor ikke-tumorcanceren er en hæmopoietisk cancer.
13. Forbindelse med formlen XIII, XIV, XV eller XVI, som defineret i et hvilket som helst af kravene 1 til 9, til anvendelse ved behandling af smerte eller inflammation.
14. Forbindelse med formlen XIII, XIV, XV eller XVI, som defineret i et hvilket som helst af kravene 1 til 9, til anvendelse ved hæmning af angiogenese.
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PT2061765E (pt) 2015-02-06
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