HRP20150962T2 - Postupak za pripremu atazanavir bisulfata i novih oblika - Google Patents
Postupak za pripremu atazanavir bisulfata i novih oblika Download PDFInfo
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- HRP20150962T2 HRP20150962T2 HRP20150962TT HRP20150962T HRP20150962T2 HR P20150962 T2 HRP20150962 T2 HR P20150962T2 HR P20150962T T HRP20150962T T HR P20150962TT HR P20150962 T HRP20150962 T HR P20150962T HR P20150962 T2 HRP20150962 T2 HR P20150962T2
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- Prior art keywords
- atazanavir
- free base
- bisulfate
- sulfuric acid
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- AXRYRYVKAWYZBR-UHFFFAOYSA-N Atazanavir Natural products C=1C=C(C=2N=CC=CC=2)C=CC=1CN(NC(=O)C(NC(=O)OC)C(C)(C)C)CC(O)C(NC(=O)C(NC(=O)OC)C(C)(C)C)CC1=CC=CC=C1 AXRYRYVKAWYZBR-UHFFFAOYSA-N 0.000 title claims 32
- 108010019625 Atazanavir Sulfate Proteins 0.000 title claims 32
- 229960003277 atazanavir Drugs 0.000 title claims 32
- AXRYRYVKAWYZBR-GASGPIRDSA-N atazanavir Chemical compound C([C@H](NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)[C@@H](O)CN(CC=1C=CC(=CC=1)C=1N=CC=CC=1)NC(=O)[C@@H](NC(=O)OC)C(C)(C)C)C1=CC=CC=C1 AXRYRYVKAWYZBR-GASGPIRDSA-N 0.000 title claims 28
- QAOWNCQODCNURD-UHFFFAOYSA-M hydrogensulfate Chemical compound OS([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 title claims 19
- 238000004519 manufacturing process Methods 0.000 title claims 2
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 26
- 238000000034 method Methods 0.000 claims 19
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 18
- 239000012458 free base Substances 0.000 claims 18
- 239000013078 crystal Substances 0.000 claims 17
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 14
- 239000002253 acid Substances 0.000 claims 11
- 238000002425 crystallisation Methods 0.000 claims 9
- 230000008025 crystallization Effects 0.000 claims 9
- 238000011049 filling Methods 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 8
- 150000001875 compounds Chemical class 0.000 claims 7
- 238000002360 preparation method Methods 0.000 claims 6
- 150000003839 salts Chemical group 0.000 claims 6
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims 5
- 150000002148 esters Chemical class 0.000 claims 5
- 239000000463 material Substances 0.000 claims 5
- 239000003960 organic solvent Substances 0.000 claims 5
- 239000002585 base Substances 0.000 claims 4
- 238000001035 drying Methods 0.000 claims 4
- 239000011541 reaction mixture Substances 0.000 claims 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical group N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims 3
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical group [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
- ZPWVASYFFYYZEW-UHFFFAOYSA-L dipotassium hydrogen phosphate Chemical compound [K+].[K+].OP([O-])([O-])=O ZPWVASYFFYYZEW-UHFFFAOYSA-L 0.000 claims 3
- 229910000396 dipotassium phosphate Inorganic materials 0.000 claims 3
- 235000019797 dipotassium phosphate Nutrition 0.000 claims 3
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 2
- 230000015572 biosynthetic process Effects 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims 2
- 238000001757 thermogravimetry curve Methods 0.000 claims 2
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 229910000288 alkali metal carbonate Inorganic materials 0.000 claims 1
- 150000008041 alkali metal carbonates Chemical class 0.000 claims 1
- 150000008044 alkali metal hydroxides Chemical group 0.000 claims 1
- 229910000318 alkali metal phosphate Inorganic materials 0.000 claims 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 claims 1
- -1 alkaline earth metal carbonate Chemical class 0.000 claims 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 claims 1
- 229910000316 alkaline earth metal phosphate Inorganic materials 0.000 claims 1
- 238000002447 crystallographic data Methods 0.000 claims 1
- 238000000113 differential scanning calorimetry Methods 0.000 claims 1
- 238000009472 formulation Methods 0.000 claims 1
- 238000010438 heat treatment Methods 0.000 claims 1
- 239000001095 magnesium carbonate Substances 0.000 claims 1
- ZLNQQNXFFQJAID-UHFFFAOYSA-L magnesium carbonate Chemical compound [Mg+2].[O-]C([O-])=O ZLNQQNXFFQJAID-UHFFFAOYSA-L 0.000 claims 1
- 235000014380 magnesium carbonate Nutrition 0.000 claims 1
- 229910000021 magnesium carbonate Inorganic materials 0.000 claims 1
- VTHJTEIRLNZDEV-UHFFFAOYSA-L magnesium dihydroxide Chemical compound [OH-].[OH-].[Mg+2] VTHJTEIRLNZDEV-UHFFFAOYSA-L 0.000 claims 1
- 239000000347 magnesium hydroxide Substances 0.000 claims 1
- 235000012254 magnesium hydroxide Nutrition 0.000 claims 1
- 229910001862 magnesium hydroxide Inorganic materials 0.000 claims 1
- 238000002156 mixing Methods 0.000 claims 1
- 238000010899 nucleation Methods 0.000 claims 1
- 150000007530 organic bases Chemical class 0.000 claims 1
- 229910000027 potassium carbonate Inorganic materials 0.000 claims 1
- 235000015320 potassium carbonate Nutrition 0.000 claims 1
- 235000011118 potassium hydroxide Nutrition 0.000 claims 1
- 238000000634 powder X-ray diffraction Methods 0.000 claims 1
- 229910000029 sodium carbonate Inorganic materials 0.000 claims 1
- 235000017550 sodium carbonate Nutrition 0.000 claims 1
- 235000011121 sodium hydroxide Nutrition 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 239000002904 solvent Substances 0.000 claims 1
- 229910052717 sulfur Inorganic materials 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- 239000000725 suspension Substances 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/06—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom containing only hydrogen and carbon atoms in addition to the ring nitrogen atom
- C07D213/127—Preparation from compounds containing pyridine rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/36—Radicals substituted by singly-bound nitrogen atoms
- C07D213/42—Radicals substituted by singly-bound nitrogen atoms having hetero atoms attached to the substituent nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
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- Life Sciences & Earth Sciences (AREA)
- Virology (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Molecular Biology (AREA)
- Tropical Medicine & Parasitology (AREA)
- AIDS & HIV (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicinal Preparation (AREA)
- Pyridine Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Claims (27)
1. Postupak za pripremu atazanavir bisulfata u obliku kristala oblika A, koji sadrži reakciju otopine atazanavir slobodne baze u organskom otapalu, koja je aceton ili smjesa acetona i N-metilpirolidona sa prvim dijelom koncentrirane sumporne kiseline u količini takvoj da reagira sa manje od oko 15% prema težini atazanavir slobodne baze, dodavanje klica kristala oblika A atazanavir bisulfata u reakcijsku smjesu, kako se kristali atazanavir bisulfata formiraju, dodavanje dodatne koncentrirane sumporne kiseline u višestrukim stadijima na rastućoj stopi prema slijedećoj jednadžbi
[image]
gdje
Vtime = volumen sumporne kiseline koja je dodana u toku proteklog vremenskog razdoblja
Vtotal = ukupan volumen kiseline koja predstavlja 90% punjenje
time = vrijeme proteklo u kristalizaciji
time total = ukupno vrijeme kristalizacije ili ukupno vrijeme za punjenje kiseline
da se postigne formiranje kristala atazanavir bisulfata, i sušenje atazanavir bisulfata da se formiraju kristali oblika A.
2. Postupak prema patentnom zahtjevu 1 naznačen time što otopina atazanavir slobodne baze na početku reagira sa od 5 do 15% prema težini ukupne korištene količine sumporne kiseline.
3. Postupak prema patentnom zahtjevu 1 naznačen time što otopina atazanavir slobodne baze na početku reagira sa od 8 do 12% prema težini ukupne korištene količine sumporne kiseline.
4. Postupak prema patentnom zahtjevu 1 naznačen time što atazanavir slobodna baza reagira sa prvim dijelom sumporne kiseline na temperaturi unutar opsega od 35 do 55°C.
5. Postupak prema patentnom zahtjevu 1 naznačen time što je otopina atazanavir slobodne baze zagrijavana do temperature unutar opsega od 35 do 55°C prije nego što reagira sa sumpornom kiselinom.
6. Postupak prema patentnom zahtjevu 1 naznačen time što je reakcijska smjesa atazanavir slobodne baze i sumporne kiseline zasijavana sa od 0.1 do 80 težinskih % kristala oblika A na bazi težine atazanavir slobodne baze.
7. Postupak prema patentnom zahtjevu 1 naznačen time što je zasijana reakcijska smjesa zagrijavana na temperaturi unutar opsega od 35 do 55°C.
8. Postupak prema patentnom zahtjevu 1 naznačen time što, organsko otapalo za atazanavir slobodnu bazu je smjesa acetona i N-metil pirolidona.
9. Postupak za pripremu materijala obrasca C atazanavir bisulfata, koji sadrži podvrgavanje kristala oblika A atazanavir bisulfata visokoj relativnoj vlažnosti od najmanje oko 95 % RH u trajanju od najmanje 24 sata i zatim sušenje.
10. Postupak za pripremu materijala obrasca C atazanavir bisulfata, koji sadrži
(a) reakciju otopine atazanavir slobodne baze u organskom otapalu, koje je aceton ili smjesa acetona i N-metilpirolidona, sa prvim dijelom koncentrirane sumporne kiseline u količini takvoj da reagira sa manje od oko 15 % prema težini atazanavir slobodne baze, dodavanje klica kristala oblika A atazanavir bisulfata u reakcijsku smjesu, kako se kristali atazanavir bisulfata formiraju, dodavanje koncentrirane sumporne kiseline u višestrukim stadijima pri rastućoj stopi prema slijedećoj jednadžbi:
[image]
gdje
Vtime = volumen sumporne kiseline koja je dodana u toku proteklog vremenskog razdoblja
Vtotal = ukupan volumen kiseline koja predstavlja 90% punjenje
time = vrijeme proteklo u kristalizaciji
time total = ukupno vrijeme kristalizacije ili ukupno vrijeme za punjenje kiseline
da se postigne formiranje kristala atazanavir bisulfata, i sušenje atazanavir bisulfata da se formiraju kristali oblika A;
(b) suspendiranje kristala oblika A atazanavir bisulfata iz koraka (a) u vodi i sušenje suspenzije da se formira materijal obrasca C; ili
(c) podvrgavanje kristala oblika A atazanavir bisulfata iz koraka (a) visokoj relativnoj vlažnosti od više od 95%RH najmanje 24 sata da se formira materijal obrasca C ili
(d) miješanje kristala oblika A iz koraka (a) sa jednim ili više formulacijskih ekscipijenata i vlažnu granulaciju smjese dobijene direktno od materijala obrasca C u smjesi sa ekscipijentima.
11. Postupak prema patentnom zahtjevu 1 za pripremu atazanavir bisulfata
[image]
u obliku kristala oblika A, koji sadrži pripremu triamin soli strukture
[image]
i bez izolacije triamin soli, reakciju triamin soli sa aktivnim esterom kiseline strukture
[image]
i bazom u prisustvu organskog otapala da se formira otopina atazanavir slobodne baze strukture
[image]
i prevođenje slobodne baze u odgovarajuću bisulfatnu sol tretmanom otopine slobodne baze u metilen kloridu sa N-metil pirolidonom i acetonom, zagrijavanje prethodno navedene smjese da se ukloni metilen klorid i tretman prethodno navedene smjese sa sumpornom kiselinom da se formira bisulfatna sol slobodne baze gdje se sumporna kiselina dodaje na rastućoj stopi prema slijedećoj jednadžbi
[image]
gdje
Vtime = volumen sumporne kiseline koja je dodana u toku proteklog vremenskog perioda
Vtotal = ukupni volumen kiseline koja predstavlja 90% punjenje
time = vrijeme proteklo u kristalizaciji
time total = ukupno vrijeme kristalizacije ili ukupno vrijeme za punjenje kiseline.
12. Postupak prema patentnom zahtjevu 11 naznačen time što triamin sol je hidrokloridna sol
[image]
13. Postupak prema patentnom zahtjevu 11 naznačen time što aktivni ester kiseline ima strukturu
[image]
14. Postupak prema patentnom zahtjevu 11 naznačen time što,baza je hidroksid alkalnog metala, hidroksid zemnoalkalnog metala, karbonat alkalnog metala, karbonat zemnoalkalnog metala, fosfat alkalnog metala, fosfat zemnoalkalnog metala ili organska baza.
15. Postupak prema patentnom zahtjevu14 naznačen time što,baza je NaOH, KOH, Mg(OH)2, K2HPO4, MgCO3, Na2CO3, K2CO3,trietilamin, diizopropiletilamin ili N-metilmorfolin i organsko otapalo je metilen klorid, etil acetat, dikloroetan, tetrahidrofuran, acetonitrile ili N,N-dimetilformamid.
16. Postupak prema patentnom zahtjevu 11 naznačen time što triamin sol i aktivni ester su reagirali na temperaturi unutar opsega od 30 do 40°C.
17. Postupak prema patentnom zahtjevu 16 naznačen time što su triamin sol i aktivni ester reagirali u prisustvu K2HPO4kao baze i metilen klorida kao otapala.
18. Postupak prema patentnom zahtjevu 11 uključujući korak zasijavanja smjese slobodne baze, acetona i N-metilpirolidona sa kristalima atazanavir bisulfata.
19. Postupak za pripremu atazanavir bisulfata
[image]
koji sadrži pripremu triamin hidrokloridne soli strukture
[image]
reakciju triamin hidrokloridne soli sa aktivnim esterom strukture
[image]
i K2HPO4u prisustvu metilen klorida da se formira otopina slobodne baze strukture
[image]
u metilen kloridu, i prevođenje slobodne baze u odgovarajuću bisulfatnu sol preko tehnike kubne kristalizacije gdje se
sumporna kiselina dodaje pri rastućoj stopi prema slijedećoj jednadžbi
[image]
gdje
Vtime = volumen sumporne kiseline koja je dodana u toku proteklog vremenskog razdoblja
Vtotal = ukupni volumen kiseline koja predstavlja 90% punjenje
time = vrijeme proteklo u kristalizaciji
time total = ukupno vrijeme kristalizacije ili ukupno vrijeme za punjenje kiseline.
20. Oblik E3 atazanavirbisulfata.
21. Spoj prema patentnom zahtjevu 20 pripremljen kao trietanolat solvat atazanavir bisulfata.
22. Spoj prema patentnom zahtjevu 20 kao što je naznačen obrascem rendgenske digfrakcije praha značajno u skladu sa onim prikazanim na Slici 9.
23. Spoj prema patentnom zahtjevu 20 koji ima kristalnu strukturu značajno prikazanu na Slici 10.
24. Spoj prema patentnom zahtjevu 20 koji je naznačen frakcijskim atomskim koordinatama značajno kao što su navedene u Tabeli 6.
25. Spoj prema patentnom zahtjevu 20 koji je naznačen kristalografskim podacima značajno jednakim slijedećim:
stanične dimenzije:
a =10.749(5) Å
b= 13.450(4) Å
c = 9.250(2) Å
α = 98.33(2)°
β = 95.92(3)°
γ= 102.82(3)°
prostorna grupa P1
molekule/asimetrična jedinica 1
gdje je navedeni kristalni oblik na oko -23°C.
26. Spoj prema patentnom zahtjevu 20 koji je naznačen podacima termograma diferencijalne skenirajuće kalorimetrije značajno u skladu sa onim prikazanim na Slici 11.
27. Spoj prema patentnom zahtjevu 20 koji je naznačen krivuljom termalne gravimetrijske analize značajno u skladu sa onom prikazanom na Slici 11.
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US56804304P | 2004-05-04 | 2004-05-04 | |
| US60753304P | 2004-09-07 | 2004-09-07 | |
| US11/119,558 US7829720B2 (en) | 2004-05-04 | 2005-05-02 | Process for preparing atazanavir bisulfate and novel forms |
| PCT/US2005/015333 WO2005108349A2 (en) | 2004-05-04 | 2005-05-03 | Process for preparing atazanavir bisulfate and novel forms |
| EP05744537.1A EP1755596B9 (en) | 2004-05-04 | 2005-05-03 | Process for preparing atazanavir bisulfate and novel forms |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HRP20150962T1 HRP20150962T1 (en) | 2015-10-09 |
| HRP20150962T2 true HRP20150962T2 (hr) | 2016-04-08 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HRP20150962TT HRP20150962T2 (hr) | 2004-05-04 | 2015-09-11 | Postupak za pripremu atazanavir bisulfata i novih oblika |
Country Status (20)
| Country | Link |
|---|---|
| US (3) | US7829720B2 (hr) |
| EP (3) | EP2669273A1 (hr) |
| JP (1) | JP5086069B2 (hr) |
| KR (1) | KR101153606B1 (hr) |
| AU (2) | AU2005240622B2 (hr) |
| BR (1) | BRPI0509595B8 (hr) |
| CA (2) | CA2777216A1 (hr) |
| CY (1) | CY1116919T1 (hr) |
| DK (1) | DK1755596T5 (hr) |
| ES (1) | ES2552219T3 (hr) |
| HR (1) | HRP20150962T2 (hr) |
| HU (1) | HUE026242T2 (hr) |
| IL (1) | IL178965A (hr) |
| MX (1) | MXPA06012612A (hr) |
| NO (1) | NO341013B1 (hr) |
| PL (1) | PL1755596T3 (hr) |
| PT (1) | PT1755596E (hr) |
| RS (1) | RS54284B1 (hr) |
| SI (1) | SI1755596T1 (hr) |
| WO (1) | WO2005108349A2 (hr) |
Families Citing this family (21)
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| TW200534879A (en) * | 2004-03-25 | 2005-11-01 | Bristol Myers Squibb Co | Coated tablet formulation and method |
| US20050256314A1 (en) * | 2004-05-04 | 2005-11-17 | Soojin Kim | Process employing controlled crystallization in forming crystals of a pharmaceutical |
| US7829720B2 (en) | 2004-05-04 | 2010-11-09 | Bristol-Myers Squibb Company | Process for preparing atazanavir bisulfate and novel forms |
| TWI415635B (zh) | 2004-05-28 | 2013-11-21 | 必治妥施貴寶公司 | 加衣錠片調製物及製備彼之方法 |
| US7642049B2 (en) * | 2006-06-30 | 2010-01-05 | Bristol-Myers Squibb Company | Method for identifying HIV-1 protease inhibitors with reduced metabolic affects through detection of human resistin polymorphisms |
| JP2010529196A (ja) | 2007-06-12 | 2010-08-26 | コンサート ファーマシューティカルズ インコーポレイテッド | アザペプチド誘導体 |
| ES2449074T3 (es) * | 2007-06-22 | 2014-03-18 | Bristol-Myers Squibb Holdings Ireland | Composiciones en forma de comprimidos que contienen atazanavir |
| MX2009013499A (es) * | 2007-06-22 | 2010-01-18 | Bristol Myers Squibb Co | Composiciones comprimidas que contienen atazanavir. |
| KR20100033378A (ko) * | 2007-06-22 | 2010-03-29 | 브리스톨-마이어스 스큅 컴퍼니 | 아타자나비르를 함유하는 정제 조성물 |
| ATE503467T1 (de) * | 2007-06-22 | 2011-04-15 | Bristol Myers Squibb Co | Tablettierte atazanavirhaltige zusammensetzungen |
| EP2376452A4 (en) | 2009-01-12 | 2012-08-29 | Hetero Research Foundation | NEW SULFATE POLYMORPH OF ATAZANAVIR |
| WO2011027324A1 (en) | 2009-09-03 | 2011-03-10 | Ranbaxy Laboratories Limited | Polymorphic forms of atazanavir sulfate |
| CA2777937C (en) | 2009-10-26 | 2017-08-29 | Merck Sharp & Dohme Corp. | Solid pharmaceutical compositions containing an integrase inhibitor |
| JP6158702B2 (ja) | 2010-04-09 | 2017-07-05 | ブリストル−マイヤーズ・スクイブ・ホールディングス・アイルランドＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｈｏｌｄｉｎｇｓ Ｉｒｅｌａｎｄ | ｐＨの影響を改善したアタザナビル硫酸塩製剤 |
| CA2849546A1 (en) | 2010-09-28 | 2012-04-05 | Ratiopharm Gmbh | Dry processing of atazanavir |
| US20140343290A1 (en) | 2011-07-27 | 2014-11-20 | Rakesh Kumar Singh | Process for the preparation of atazanavir or its bisulfate salt |
| US8461347B2 (en) | 2011-08-05 | 2013-06-11 | Scinopharm Taiwan, Ltd. | Process for preparing form A of atazanavir sulfate |
| WO2014030173A2 (en) * | 2012-08-24 | 2014-02-27 | Laurus Labs Private Limited | An improved process for the preparation of atazanavir bisulfate |
| WO2014036690A1 (zh) * | 2012-09-04 | 2014-03-13 | 上海迪赛诺化学制药有限公司 | 制备阿扎那韦硫酸氢盐a型结晶的方法 |
| EP2956439B1 (en) | 2013-02-12 | 2019-01-09 | Cipla Limited | Process for preparing atazanavir sulphate |
| CN115215792A (zh) * | 2022-06-27 | 2022-10-21 | 江西富祥药业股份有限公司 | 一种制备阿扎那韦或其硫酸盐的方法 |
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| GB9407386D0 (en) | 1994-04-14 | 1994-06-08 | Smithkline Beecham Plc | Pharmaceutical formulation |
| TW483763B (en) | 1994-09-02 | 2002-04-21 | Astra Ab | Pharmaceutical composition comprising of ramipril and dihydropyridine compound |
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| US5849911A (en) | 1996-04-22 | 1998-12-15 | Novartis Finance Corporation | Antivirally active heterocyclic azahexane derivatives |
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| EP1165521A4 (en) | 1999-03-22 | 2002-05-22 | Bristol Myers Squibb Co | FUSED COMPOUNDS OF PYRIDOPYRIDAZINE CGMP PHOSPHODIESTERASE INHIBITORS |
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| WO2001034148A1 (fr) | 1999-11-11 | 2001-05-17 | Kyorin Pharmaceutical Co., Ltd. | Preparations solides pour administration orale |
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| TW200534879A (en) | 2004-03-25 | 2005-11-01 | Bristol Myers Squibb Co | Coated tablet formulation and method |
| US7829720B2 (en) | 2004-05-04 | 2010-11-09 | Bristol-Myers Squibb Company | Process for preparing atazanavir bisulfate and novel forms |
| US20050256314A1 (en) | 2004-05-04 | 2005-11-17 | Soojin Kim | Process employing controlled crystallization in forming crystals of a pharmaceutical |
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-
2005
- 2005-05-02 US US11/119,558 patent/US7829720B2/en active Active
- 2005-05-03 EP EP20130175944 patent/EP2669273A1/en not_active Withdrawn
- 2005-05-03 EP EP15180557.9A patent/EP2980074A1/en not_active Ceased
- 2005-05-03 CA CA2777216A patent/CA2777216A1/en not_active Abandoned
- 2005-05-03 DK DK05744537.1T patent/DK1755596T5/en active
- 2005-05-03 PL PL05744537T patent/PL1755596T3/pl unknown
- 2005-05-03 CA CA2565629A patent/CA2565629C/en active Active
- 2005-05-03 EP EP05744537.1A patent/EP1755596B9/en active Active
- 2005-05-03 RS RS20150653A patent/RS54284B1/en unknown
- 2005-05-03 AU AU2005240622A patent/AU2005240622B2/en active Active
- 2005-05-03 PT PT57445371T patent/PT1755596E/pt unknown
- 2005-05-03 JP JP2007511502A patent/JP5086069B2/ja active Active
- 2005-05-03 SI SI200532001T patent/SI1755596T1/sl unknown
- 2005-05-03 KR KR1020067025370A patent/KR101153606B1/ko active IP Right Grant
- 2005-05-03 BR BRPI0509595A patent/BRPI0509595B8/pt active IP Right Grant
- 2005-05-03 HU HUE05744537A patent/HUE026242T2/en unknown
- 2005-05-03 ES ES05744537.1T patent/ES2552219T3/es active Active
- 2005-05-03 WO PCT/US2005/015333 patent/WO2005108349A2/en active Application Filing
- 2005-05-03 MX MXPA06012612A patent/MXPA06012612A/es active IP Right Grant
-
2006
- 2006-10-31 IL IL178965A patent/IL178965A/en active IP Right Grant
- 2006-11-27 NO NO20065441A patent/NO341013B1/no unknown
-
2009
- 2009-01-27 US US12/360,468 patent/US7838678B2/en active Active
-
2010
- 2010-04-16 AU AU2010201538A patent/AU2010201538B2/en active Active
- 2010-10-08 US US12/900,588 patent/US8513428B2/en active Active
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2015
- 2015-09-11 HR HRP20150962TT patent/HRP20150962T2/hr unknown
- 2015-11-10 CY CY20151101005T patent/CY1116919T1/el unknown
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