DK2495307T5 - Fremstilling af koagulationsfaktor IX med forbedret glycosyleringsmønster - Google Patents
Fremstilling af koagulationsfaktor IX med forbedret glycosyleringsmønster Download PDFInfo
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Claims (21)
1. Forbindelse med formlen I:
hvor: n er valgt blandt 0, 1 og 2; m er valgt blandt 0, 1 og 2; X er valgt blandt O og NR6; hvor R6 er Ci^alkyl; Yi er valgt blandt N og CR7; hvor R7 er valgt blandt hydrogen og Ci^alkyl; Ri er hydrogen; R2 er valgt blandt hydrogen og halogen; R3 er valgt blandt -CH2CH2R8b og -CR8a=CR8aR8b; hvor R8a uafhængigt er valgt blandt hydrogen, fluor og Ci-4alkyl; og Reb er valgt blandt -C(0)0R9a, - C(0)NR9aR9b, -C(0)NH0R9a, -C(0)X2R9a og en 5-6 leddet heteroaryl valgt blandt:
hvor den punkterede linie indikerer forbindelsespunktet med -CH2CH2 eller -CR8a=CR8a i R3; hvor X2 er Ci^alkylen; R9a og Rgb er uafhængigt valgt blandt hydrogen, Ci-4alkyl, hydroxy-substitueret-Ci-4alkyl, halogen-substitueret- Ci-4alkyl og -X4R10; hvor X4 er valgt blandt en binding og Ci-3alkylen; og R10 er en 4-6 leddet mættet ring indeholdende 1 til 3 atomer uafhængigt valgt blandt O, N og S; hvor heteroaryl i Reb er usubstitueret eller substitueret med 1 til 3 grupper uafhængigt valgt blandt Ci-4alkyl og Cs-ecycloalkyl; R4 er valgt blandt hydrogen, Ci^alkyl, halogen og Ci-3alkoxy; R5 er valgt blandt Ce-ioaryl og en 5-6 leddet heteroaryl valgt blandt:
hvor den punkterede linie indikerer forbindelsespunktet med benzothiophenkernen; hvor den nævnte C6-ioaryl eller heteroaryl i R5 er substitueret med 1 til 3 grupper valgt blandt -X3-Rsa og Rsa; hvor X3 er methylen; R5a er valgt blandt hydroxy, amino, Ci-4alkyl, halogen, nitro, cyano, halogen-substitueret-Ci^alkyl, cyano-substitueret-Ci-4alkyl, hydroxy-substitueret-Ci-4alkyl, halogen-substitueret-Ci-4alkoxy, Ci-4alkoxy, -SF5, -NRnaRub, -C(0)Rna, C3-8cycloalkyl og en 4-7 leddet mættet, umættet eller delvis mættet ring indeholdende ét til 4 heteroatomer eller grupper valgt blandt O, NH, C(O) og S(0)o-2; hvor Rna og Rub uafhængigt er valgt blandt hydrogen og Ci-4alkyl; eller Rna og Rub danner sammen med det nitrogenatom hvortil de begge er forbundet en 4 til 7 leddet mættet ring indeholdende et yderligere heteroatom eller en gruppe valgt blandt O, NH, og S(0)o-2; hvor den 4-7 leddede ring i Rsa kan være usubstitueret eller substitueret med Ci^alkyl; eller et farmaceutisk acceptabelt salt deraf.
2. Forbindelse ifølge krav 1 med formlen la:
hvor: n er valgt blandt 0, 1 og 2; m er valgt blandt 0, 1 og 2; Yi er valgt blandt N og CR7; hvor R7 er valgt blandt hydrogen og Ci^alkyl; Ri er hydrogen; R2 er valgt blandt hydrogen og halogen; R3 er valgt blandt -CH2CH2R8b og -CR8a=CR8aR8b; hvor hver R8a er uafhængigt valgt blandt hydrogen og C^alkyl; og Reb er valgt blandt -C(0)0R9a, -C(0)NR9aR9b, - C(0)NH0R9a! -C(0)X2R9a, 1,3,4-oxadiazolyl, 4H-1,2,4-triazolyl, 5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl, 2-oxo-pyrimidinyl og imidazolyl; hvor X2 er Ci-»alky-len; R9a og R9b er uafhængigt valgt blandt hydrogen, C^alkyl, hydroxy-substitueret-Ci-4alkyl, halogen-substitueret-Ci-4alkyl og -X4R10; hvorX4 er valgt blandt en binding og Ci-3alkylen; og R10 er en 4-6 leddet mættet ring indeholdende 1 til 3 atomer uafhængigt valgt blandt O, N og S; hvor den nævnte 1,3,4-oxadiazolyl, 4H-1,2,4-triazolyl, 2-oxo-pyrimidinyl eller imidazolyl af R8b er usubstitueret eller substitueret med 1 til 3 grupper uafhængigt valgt blandt C^alkyl og C3-8cycloalkyl; R4 er valgt blandt hydrogen og Ci-4alkyl; og hver Rsa er uafhængigt valgt blandt hydroxy, Ci-4alkyl, halogen, nitro, cyano, halogen-substitueret-Ci-4alkyl, halogen-substitueret-Ci-4alkoxy, hydroxy-substitueret-Ci-4alkyl, Ci-4alkoxy, C3-8cycloalkyl, -NRnaRub, -C(0)Rna og en 4-7 leddet mættet, umættet eller delvis mættet ring indeholdende ét til 4 heteroatomer eller grupper valgt blandt O, NH, C(O) og S(O)0-2; hvor Rna og Rub uafhængigt er valgt blandt hydrogen og C^alkyl; hvor den 4-7 leddede ring i R5a kan være usubstitueret eller substitueret med C^alkyl; X3 er valgt blandt en binding og methylen; eller et farmaceutisk acceptabelt salt deraf.
3. Forbindelse ifølge krav 2, hvor R3 er valgt blandt -CH2CH2R8b og -CR8a=CR8aR8b; hvor hver R8a er uafhængigt valgt blandt hydrogen og C^alkyl; og R8b er valgt blandt -C(0)0R9a, -C(0)NR9aR9b, -C(0)NH0R9a og -C(0)X2R9a; hvor X2 er Ci-4alkylen; Rga og Rgb er uafhængigt valgt blandt hydrogen, Ci^alkyl, hydroxy-substitueret-Ci-4alkyl, halogen-substitueret-Ci.4alkyl og morpholino-ethyl.
4. Forbindelse ifølge krav 3, hvor R3 er valgt blandt -CFbCFbReb og -CRea=CR8aR8b; hvor hver R8a er uafhængigt valgt blandt hydrogen og Ci-4alkyl; og Reb er uafhængigt valgt blandt -C(0)0H and-C(0)0CH3.
5. Forbindelse ifølge krav 1 eller det farmaceutisk acceptable salt deraf, valgt blandt:
6. Forbindelse ifølge krav 1 eller det farmaceutisk acceptable salt deraf, valgt blandt:
7. Forbindelse ifølge krav 2, hvor R3 er valgt blandt -CFbCFbReb og -CR8a=CR8aR8b; hvor hver R8a er uafhængigt valgt blandt hydrogen og Ci-4alkyl; og R8b er valgt blandt 1,3,4-oxadiazolyl, 4H-1,2,4-triazolyl, 5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl, 2-oxo-pyrimidinyl og imidazolyl; hvor de nævnte 1,3,4-oxadiazolyl, 4H-1,2,4-triazolyl, 2-oxo-pyrimidinyl eller imidazolyl i Reb er usubstitueret eller substitueret med 1 til 3 grupper uafhængigt valgt blandt Ci-4alkyl og C3-8cycloalkyl.
8. Forbindelse ifølge krav 1 eller det farmaceutisk acceptable salt deraf, valgt blandt:
9. Forbindelse ifølge krav 1 med formlen Ib:
hvor: n er valgt blandt 0, 1 og 2; m er valgt blandt 0, 1 og 2; Yi er valgt blandt N og CR7; hvor R7 er valgt blandt hydrogen og Ci^alkyl; Ri er hydrogen; R2 er valgt blandt hydrogen og halogen; R3 er valgt blandt -CH2CH2R8b og -CR8a=CR8aR8b; hvor hver R8a uafhængigt er valgt blandt hydrogen og Ci-4alkyl; og Reb er valgt blandt -C(0)0R9a, -C(0)NR9aR9b, - C(0)NH0R9a, -C(0)X2R9a, 1,3,4-oxadiazolyl, 4H-1,2,4-triazolyl, 5-oxo-4,5-dihydro-1,3,4-oxadiazol-2-yl, 2-oxo-pyrimidinyl og imidazolyl; hvor X2 er Ci-talky-len; R9a og R9b er uafhængigt valgt blandt hydrogen, Ci-4alkyl, hydroxy-substitueret-Ci-4alkyl og halogen-substitueret-Ci^alkyl; hvor den nævnte 1,3,4-oxadiazolyl, 4H-1,2,4-triazolyl, 2-oxo-pyrimidinyl eller imidazolyl i Reb er usubstitueret eller substitueret med en gruppe valgt blandt Ci-*alkyl og C3-8cycloalkyl; R4 er valgt blandt hydrogen og Ci-4alkyl; hver R5a er uafhængigt valgt blandt hydroxy, Ci^alkyl, halogen, nitro, cyano, halogen-substitueret-Ci-4alkyl, halogen-substitueret-Ci.4alkoxy, hydroxy-substitueret-Ci^alkyl, Ci-4alkoxy og -C(0)Rna; hvor Rna er valgt blandt hydrogen og Ci^alkyl; og R6 er Ci^alkyl; eller et farmaceutisk acceptabelt salt deraf.
10. Forbindelse ifølge krav 9, hvor R3 er valgt blandt -CFhCFhReb og -CR8a=CR8aR8b; hvor hver Rsa er uafhængigt valgt blandt hydrogen og Ci-»alkyl; og Reb er valgt blandt - C(0)0Rga, -C(0)NR9aR9b, -C(0)NH0R9a og -C(0)X2R9a; hvor X2 er Ci-4alkylen; R9a og Rgb er uafhængigt valgt blandt hydrogen, Ci^alkyl, hydroxy-substitueret-Ci-4alkyl og halogen-sub stituted-C i-»alkyl.
11. Forbindelse ifølge krav 10 eller det farmaceutisk acceptable salt deraf valgt blandt:
12. Forbindelse eller de farmaceutisk acceptable salte deraf, valgt blandt:
13. Forbindelse ifølge krav 1 eller et farmacedutisk acceptabelt salt deraf, som har strukturen:
14. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf, som har strukturen:
15. Farmaceutisk sammensætning omfattende en forbindelse ifølge krav 1 blandet med i det mindste et farmaceutisk acceptabelt excipiens.
16. Farmaceutisk sammensætning ifølge krav 15, som yderligere omfatter et yderligere terapeutisk middel.
17. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf, i kombination med en anden farmakologisk aktiv forbindelse, eller med to eller flere andre farmakologisk aktive forbindelser.
18. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf, i kombinationer som angivet i krav 17, hvor de farmakologisk aktive forbindelser er ét eller flere kemoterapimidler.
19. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf, til anvendelse som et medikament.
20. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf til anvendelse ifølge krav 19, hvor af medikamentet til behandlingen af cancer.
21. Forbindelse ifølge krav 1 eller et farmaceutisk acceptabelt salt deraf til anvendelse ved behandlingen af cancer som angivet i krav 20, hvor canceren er blandt brystcancer, æggestokcancer, endometrial cancer, prostatacancer, livmodercancer, livmoderhalscancer og lungecancer.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US83065806P | 2006-07-13 | 2006-07-13 | |
| EP20070796784 EP2041270B1 (en) | 2006-07-13 | 2007-07-11 | Production of glycoproteins |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| DK2495307T3 DK2495307T3 (da) | 2018-05-07 |
| DK2495307T5 true DK2495307T5 (da) | 2018-07-16 |
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Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK17179340.9T DK3255141T3 (da) | 2006-07-13 | 2007-07-11 | Fremstilling af antistoffer med forbedret glycosyleringsmønster |
| DK12164058.5T DK2495307T5 (da) | 2006-07-13 | 2007-07-11 | Fremstilling af koagulationsfaktor IX med forbedret glycosyleringsmønster |
| DK07796784T DK2041270T3 (da) | 2006-07-13 | 2007-07-11 | Fremstilling af glycoproteiner |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK17179340.9T DK3255141T3 (da) | 2006-07-13 | 2007-07-11 | Fremstilling af antistoffer med forbedret glycosyleringsmønster |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DK07796784T DK2041270T3 (da) | 2006-07-13 | 2007-07-11 | Fremstilling af glycoproteiner |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US8129145B2 (da) |
| EP (3) | EP2041270B1 (da) |
| JP (1) | JP5401310B2 (da) |
| KR (1) | KR101495549B1 (da) |
| CN (2) | CN101541950A (da) |
| AR (1) | AR061976A1 (da) |
| AU (1) | AU2007272957B2 (da) |
| BR (1) | BRPI0714212B8 (da) |
| CA (1) | CA2657248C (da) |
| DK (3) | DK3255141T3 (da) |
| ES (2) | ES2668212T3 (da) |
| HK (1) | HK1214307A1 (da) |
| HU (1) | HUE039128T2 (da) |
| IL (1) | IL196252A (da) |
| MX (1) | MX2009000349A (da) |
| PE (1) | PE20081194A1 (da) |
| PL (2) | PL2041270T3 (da) |
| PT (2) | PT2041270E (da) |
| RU (1) | RU2463345C2 (da) |
| SI (1) | SI2495307T1 (da) |
| TR (1) | TR201807021T4 (da) |
| TW (1) | TW200812577A (da) |
| WO (1) | WO2008008360A1 (da) |
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| CA2679941C (en) * | 2007-03-02 | 2016-09-20 | Wyeth | Use of copper and glutamate in cell culture for production of polypeptides |
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| TW201028433A (en) | 2008-10-20 | 2010-08-01 | Abbott Lab | Viral inactivation during purification of antibodies |
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