DK2552930T3 - Krystallinsk (s)-isopropyl 2-(((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4-dihydropyrimidin- 1-(2h)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)amino)propanoat - Google Patents
Krystallinsk (s)-isopropyl 2-(((s)-(((2r,3r,4r,5r)-5-(2,4-dioxo-3,4-dihydropyrimidin- 1-(2h)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)amino)propanoat Download PDFInfo
- Publication number
- DK2552930T3 DK2552930T3 DK11714465.9T DK11714465T DK2552930T3 DK 2552930 T3 DK2552930 T3 DK 2552930T3 DK 11714465 T DK11714465 T DK 11714465T DK 2552930 T3 DK2552930 T3 DK 2552930T3
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- Prior art keywords
- phenoxy
- mixture
- crystalline
- isopropyl
- fluoro
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Classifications
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- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
- C07H19/02—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing nitrogen
- C07H19/04—Heterocyclic radicals containing only nitrogen atoms as ring hetero atom
- C07H19/16—Purine radicals
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- A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
- A61K31/706—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom
- A61K31/7064—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines
- A61K31/7068—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
- A61K31/7072—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing six-membered rings with nitrogen as a ring hetero atom containing condensed or non-condensed pyrimidines having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid having two oxo groups directly attached to the pyrimidine ring, e.g. uridine, uridylic acid, thymidine, zidovudine
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- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
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- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/2404—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic
- C07F9/242—Esteramides the ester moiety containing a substituent or a structure which is considered as characteristic of hydroxyaryl compounds
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- C07F9/2458—Esteramides the amide moiety containing a substituent or a structure which is considered as characteristic of aliphatic amines
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65515—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring
- C07F9/65517—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a five-membered ring condensed with carbocyclic rings or carbocyclic ring systems
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
- C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
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- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
- C07F9/65616—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings containing the ring system having three or more than three double bonds between ring members or between ring members and non-ring members, e.g. purine or analogs
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Claims (19)
- KRYSTALLINSK (S)-ISOPROPYL 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-DIOXO-3,4-DIHYDROPYRIMIDIN-1 -(2H)-YL)-4-FLUOR-3-HYDROXY -4-METHYLTETRAHYDROFURAN-2-YL)METHOXY)(PHENOXY)PHOSPHORYL)AMINO)PROPANOAT1. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat repræsenteret af formlen SP-4:Sp-4 der har XRPD 20-reflektioner (°) ved omkring: 6,1, 8,2, 10,4, 12,7, 17,2, 17,7, 18,0, 18,8, 19,4, 19,8,20,1,20,8,21,8 og 23,3.
- 2. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1, der har XRPD 20-reflektioner (°) ved omkring: 6,08, 8,2, 10,38, 10,85, 12,17, 12,7, 13,73, 14,1, 15,91, 16,83, 17,17, 17,66, 17,95, 18,79, 19,1, 19,41, 19,8, 20,11, 20,82, 21,81, 22,03, 23,03, 23,26, 23,64, 23,89 og 24,73 med intensiteter (%) på henholdsvis 66,7, 62,1, 29,8, 10,4, 12,0, 66,4, 14,9, 13,8, 3,1, 8,7, 19,7, 56,2, 37,7, 59,0, 14,3, 37,2, 46,0, 68,8, 100,0, 36,8, 7,4, 14,2, 21,6, 6,3, 7,0 og 3,3.
- 3. Farmaceutisk sammensætning, der omfatter krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1 eller 2 og et farmaceutisk acceptabelt medium.
- 4. Farmaceutisk sammensætning ifølge krav 3, hvilken sammensætning endvidere omfatter et andet antiviralt middel.
- 5. Farmaceutisk sammensætning ifølge krav 4, hvor det andet antivirale middel er en HCV NS3-proteaseinhibitor.
- 6. Farmaceutisk sammensætning ifølge krav 4, hvor det andet antivirale middel er en HCV NS5A-inhibitor.
- 7. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofiiran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1 eller 2 til anvendelse som et medikament.
- 8. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofiiran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1 eller 2 til anvendelse i behandling af en hepatitis C-virusinfektion.
- 9. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)- 4-fluor-3-hydroxy-4-methyltetrahydrofiiran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat til anvendelse ifølge krav 8 til anvendelse i kombination med et andet antiviralt middel.
- 10. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)- 4-fluor-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(pbenoxy)pbospboryl)amino)propanoat til anvendelse ifølge krav 9, hvor det andet antivirale middel er en HCV NS3-proteaseinhibitor.
- 11. Krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)- 4-fluor-3-hydroxy-4-methyltetrahydrofuran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat til anvendelse ifølge krav 9, hvor det andet antivirale middel er en HCV NS5A-inhibitor.
- 12. Medikament, der omfatter krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4-dihydropyrimidin-l(2H)-yl)-4-fLuor-3-hydroxy-4-methyltetrahydrofiiran-2-yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1 eller 2.
- 13. Medikament ifølge krav 12, hvilket medikament endvidere omfatter et andet antiviralt middel.
- 14. Medikament ifølge krav 13, hvor det andet antivirale middel er en HCV NS3-proteaseinhibitor.
- 15. Medikament ifølge krav 13, hvor det andet antivirale middel er en HCV NS5A-inhibitor.
- 16. Anvendelse af en krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4- dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1 eller 2 i fremstillingen af et medikament til behandling af en hepatitis C-virusinfektion.
- 17. Anvendelse af en krystallinsk (S)-isopropyl 2-(((S)-(((2R,3R,4R,5R)-5-(2,4-dioxo-3,4- dihydropyrimidin-l(2H)-yl)-4-fluor-3-hydroxy-4-methyltetrahydrofuran-2- yl)methoxy)(phenoxy)phosphoryl)amino)propanoat ifølge krav 1 eller 2 og et andet antiviralt middel til fremstilling af et medikament til behandling af en hepatitis C virusinfection.
- 18. Anvendelse ifølge krav 17, hvor det andet antivirale middel er en HCV NS3-proteaseinhibitor.
- 19. Anvendelse ifølge krav 17, hvor det andet antivirale middel er en HCV NS5A-inhibitor.
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US12/783,680 US8642756B2 (en) | 2009-05-20 | 2010-05-20 | Nucleoside phosphoramidates |
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DK13159791.6T DK2609923T3 (da) | 2010-03-31 | 2011-03-31 | Fremgangsmåde til krystallisering af (s)-isopropyl 2- (((s)(perfluorphenoxy)(phenoxy)phosphoryl)amino)propanoat |
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