HRP20130993T1 - Novi polimorfni oblici 6-(1-metil-1h-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2h-piridazin-3-on dihidrogenfosfata i postupak njihove proizvodnje - Google Patents
Novi polimorfni oblici 6-(1-metil-1h-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2h-piridazin-3-on dihidrogenfosfata i postupak njihove proizvodnje Download PDFInfo
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- HRP20130993T1 HRP20130993T1 HRP20130993AT HRP20130993T HRP20130993T1 HR P20130993 T1 HRP20130993 T1 HR P20130993T1 HR P20130993A T HRP20130993A T HR P20130993AT HR P20130993 T HRP20130993 T HR P20130993T HR P20130993 T1 HRP20130993 T1 HR P20130993T1
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- pyridazin
- morpholin
- pyrazol
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- ZJLNMCIVKXVBKW-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-2-[[3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]phenyl]methyl]pyridazin-3-one;phosphoric acid Chemical compound OP(O)(O)=O.C1=NN(C)C=C1C1=NN(CC=2C=C(C=CC=2)C=2N=CC(OCCN3CCOCC3)=CN=2)C(=O)C=C1 ZJLNMCIVKXVBKW-UHFFFAOYSA-N 0.000 title claims 12
- 238000004519 manufacturing process Methods 0.000 title claims 9
- 238000000034 method Methods 0.000 title claims 9
- 230000004048 modification Effects 0.000 claims 25
- 238000012986 modification Methods 0.000 claims 25
- 150000001875 compounds Chemical class 0.000 claims 19
- 239000002904 solvent Substances 0.000 claims 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims 14
- 239000006185 dispersion Substances 0.000 claims 14
- 238000003756 stirring Methods 0.000 claims 14
- 206010028980 Neoplasm Diseases 0.000 claims 11
- 239000011877 solvent mixture Substances 0.000 claims 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 9
- 239000013078 crystal Substances 0.000 claims 9
- 230000005855 radiation Effects 0.000 claims 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 8
- 239000000203 mixture Substances 0.000 claims 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical class OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims 7
- 238000001914 filtration Methods 0.000 claims 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
- 238000001816 cooling Methods 0.000 claims 6
- 238000002156 mixing Methods 0.000 claims 6
- 238000001035 drying Methods 0.000 claims 5
- 238000005406 washing Methods 0.000 claims 5
- CIUKPBWULKEZMF-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-2-[[3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]phenyl]methyl]pyridazin-3-one Chemical compound C1=NN(C)C=C1C1=NN(CC=2C=C(C=CC=2)C=2N=CC(OCCN3CCOCC3)=CN=2)C(=O)C=C1 CIUKPBWULKEZMF-UHFFFAOYSA-N 0.000 claims 4
- 201000009030 Carcinoma Diseases 0.000 claims 4
- 238000002441 X-ray diffraction Methods 0.000 claims 4
- 201000011510 cancer Diseases 0.000 claims 4
- 238000002425 crystallisation Methods 0.000 claims 4
- 230000008025 crystallization Effects 0.000 claims 4
- 239000012458 free base Substances 0.000 claims 4
- 238000011084 recovery Methods 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 239000013543 active substance Substances 0.000 claims 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims 3
- 238000009826 distribution Methods 0.000 claims 3
- 239000003814 drug Substances 0.000 claims 3
- 229940079593 drug Drugs 0.000 claims 3
- 239000012266 salt solution Substances 0.000 claims 3
- 239000000243 solution Substances 0.000 claims 3
- 239000000758 substrate Substances 0.000 claims 3
- WFVHMQZSPMBNBF-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-2-[[3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]phenyl]methyl]pyridazin-3-one;phosphoric acid;dihydrate Chemical compound O.O.OP(O)(O)=O.C1=NN(C)C=C1C1=NN(CC=2C=C(C=CC=2)C=2N=CC(OCCN3CCOCC3)=CN=2)C(=O)C=C1 WFVHMQZSPMBNBF-UHFFFAOYSA-N 0.000 claims 2
- ODKSRZOWMQDJNA-UHFFFAOYSA-N 6-(1-methylpyrazol-4-yl)-2-[[3-[5-(2-morpholin-4-ylethoxy)pyrimidin-2-yl]phenyl]methyl]pyridazin-3-one;phosphoric acid;hydrate Chemical compound O.OP(O)(O)=O.C1=NN(C)C=C1C1=NN(CC=2C=C(C=CC=2)C=2N=CC(OCCN3CCOCC3)=CN=2)C(=O)C=C1 ODKSRZOWMQDJNA-UHFFFAOYSA-N 0.000 claims 2
- 206010005003 Bladder cancer Diseases 0.000 claims 2
- 206010006187 Breast cancer Diseases 0.000 claims 2
- 208000026310 Breast neoplasm Diseases 0.000 claims 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
- 208000008839 Kidney Neoplasms Diseases 0.000 claims 2
- 208000000236 Prostatic Neoplasms Diseases 0.000 claims 2
- 206010038389 Renal cancer Diseases 0.000 claims 2
- 206010039491 Sarcoma Diseases 0.000 claims 2
- 208000007097 Urinary Bladder Neoplasms Diseases 0.000 claims 2
- 239000007864 aqueous solution Substances 0.000 claims 2
- 238000001704 evaporation Methods 0.000 claims 2
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- 238000011534 incubation Methods 0.000 claims 2
- 230000005764 inhibitory process Effects 0.000 claims 2
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- 230000002265 prevention Effects 0.000 claims 2
- 201000005112 urinary bladder cancer Diseases 0.000 claims 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- FPYJSJDOHRDAMT-KQWNVCNZSA-N 1h-indole-5-sulfonamide, n-(3-chlorophenyl)-3-[[3,5-dimethyl-4-[(4-methyl-1-piperazinyl)carbonyl]-1h-pyrrol-2-yl]methylene]-2,3-dihydro-n-methyl-2-oxo-, (3z)- Chemical compound C=1C=C2NC(=O)\C(=C/C3=C(C(C(=O)N4CCN(C)CC4)=C(C)N3)C)C2=CC=1S(=O)(=O)N(C)C1=CC=CC(Cl)=C1 FPYJSJDOHRDAMT-KQWNVCNZSA-N 0.000 claims 1
- 206010000830 Acute leukaemia Diseases 0.000 claims 1
- 208000014697 Acute lymphocytic leukaemia Diseases 0.000 claims 1
- 208000031261 Acute myeloid leukaemia Diseases 0.000 claims 1
- 208000010507 Adenocarcinoma of Lung Diseases 0.000 claims 1
- 208000010839 B-cell chronic lymphocytic leukemia Diseases 0.000 claims 1
- 208000032791 BCR-ABL1 positive chronic myelogenous leukemia Diseases 0.000 claims 1
- 206010004146 Basal cell carcinoma Diseases 0.000 claims 1
- 208000003174 Brain Neoplasms Diseases 0.000 claims 1
- 206010008342 Cervix carcinoma Diseases 0.000 claims 1
- 208000010833 Chronic myeloid leukaemia Diseases 0.000 claims 1
- 208000001333 Colorectal Neoplasms Diseases 0.000 claims 1
- 206010014759 Endometrial neoplasm Diseases 0.000 claims 1
- 208000000461 Esophageal Neoplasms Diseases 0.000 claims 1
- 208000006168 Ewing Sarcoma Diseases 0.000 claims 1
- 208000009849 Female Genital Neoplasms Diseases 0.000 claims 1
- 201000003741 Gastrointestinal carcinoma Diseases 0.000 claims 1
- 206010018338 Glioma Diseases 0.000 claims 1
- 206010019695 Hepatic neoplasm Diseases 0.000 claims 1
- 206010061252 Intraocular melanoma Diseases 0.000 claims 1
- 208000007766 Kaposi sarcoma Diseases 0.000 claims 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 claims 1
- 208000031422 Lymphocytic Chronic B-Cell Leukemia Diseases 0.000 claims 1
- 206010025323 Lymphomas Diseases 0.000 claims 1
- 208000015021 Meningeal Neoplasms Diseases 0.000 claims 1
- 208000033761 Myelogenous Chronic BCR-ABL Positive Leukemia Diseases 0.000 claims 1
- 208000033776 Myeloid Acute Leukemia Diseases 0.000 claims 1
- 206010029260 Neuroblastoma Diseases 0.000 claims 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 claims 1
- 206010061535 Ovarian neoplasm Diseases 0.000 claims 1
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims 1
- 208000009565 Pharyngeal Neoplasms Diseases 0.000 claims 1
- 206010034811 Pharyngeal cancer Diseases 0.000 claims 1
- 206010060862 Prostate cancer Diseases 0.000 claims 1
- 102000001253 Protein Kinase Human genes 0.000 claims 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims 1
- 208000015634 Rectal Neoplasms Diseases 0.000 claims 1
- 201000000582 Retinoblastoma Diseases 0.000 claims 1
- 208000000453 Skin Neoplasms Diseases 0.000 claims 1
- 206010041067 Small cell lung cancer Diseases 0.000 claims 1
- 208000021712 Soft tissue sarcoma Diseases 0.000 claims 1
- 208000005718 Stomach Neoplasms Diseases 0.000 claims 1
- -1 TFH Chemical compound 0.000 claims 1
- 208000024313 Testicular Neoplasms Diseases 0.000 claims 1
- 206010057644 Testis cancer Diseases 0.000 claims 1
- 208000024770 Thyroid neoplasm Diseases 0.000 claims 1
- 208000006105 Uterine Cervical Neoplasms Diseases 0.000 claims 1
- 208000002495 Uterine Neoplasms Diseases 0.000 claims 1
- 201000005969 Uveal melanoma Diseases 0.000 claims 1
- 230000033228 biological regulation Effects 0.000 claims 1
- 238000009835 boiling Methods 0.000 claims 1
- 210000000133 brain stem Anatomy 0.000 claims 1
- 208000002458 carcinoid tumor Diseases 0.000 claims 1
- 201000010881 cervical cancer Diseases 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 claims 1
- 208000032852 chronic lymphocytic leukemia Diseases 0.000 claims 1
- 201000010902 chronic myelomonocytic leukemia Diseases 0.000 claims 1
- 208000029742 colonic neoplasm Diseases 0.000 claims 1
- 210000002808 connective tissue Anatomy 0.000 claims 1
- 238000010790 dilution Methods 0.000 claims 1
- 239000012895 dilution Substances 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 208000035475 disorder Diseases 0.000 claims 1
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- 206010017758 gastric cancer Diseases 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 230000003463 hyperproliferative effect Effects 0.000 claims 1
- 201000002313 intestinal cancer Diseases 0.000 claims 1
- 208000014018 liver neoplasm Diseases 0.000 claims 1
- 201000005249 lung adenocarcinoma Diseases 0.000 claims 1
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- 208000025440 neoplasm of neck Diseases 0.000 claims 1
- 210000000653 nervous system Anatomy 0.000 claims 1
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- 201000002575 ocular melanoma Diseases 0.000 claims 1
- 201000008968 osteosarcoma Diseases 0.000 claims 1
- 201000002528 pancreatic cancer Diseases 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 108060006633 protein kinase Proteins 0.000 claims 1
- 230000019491 signal transduction Effects 0.000 claims 1
- 201000000849 skin cancer Diseases 0.000 claims 1
- 208000000587 small cell lung carcinoma Diseases 0.000 claims 1
- 239000012453 solvate Substances 0.000 claims 1
- 201000011549 stomach cancer Diseases 0.000 claims 1
- 201000003120 testicular cancer Diseases 0.000 claims 1
- 208000008732 thymoma Diseases 0.000 claims 1
- 201000002510 thyroid cancer Diseases 0.000 claims 1
- 206010046766 uterine cancer Diseases 0.000 claims 1
- 210000004291 uterus Anatomy 0.000 claims 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- 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
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/10—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing aromatic rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
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- Life Sciences & Earth Sciences (AREA)
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- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oncology (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
Claims (31)
1. Spoj naznačen time da je kristalni 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat solvat.
2. Spoj naznačen time da je kristalni 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrat.
3. Spoj prema zahtjevu 2 u svojoj kristalnoj modifikaciji A1, koja je naznačena time da ima XRD vrške koji sadrže 3.2°, 6.5°, 9.8°, i 13.1° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
4. Spoj prema zahtjevu 2 u svojoj kristalnoj modifikaciji A1, koja je naznačena time da ima XRD vrške koji sadrže 18.4°, 18.8°, 23,7°, 24.2°, 26.4°, i 28.2° 2θ (sve ±0.1° 2θ, korištenjem Cu-Kα1 zračenja).
5. Spoj prema zahtjevu 2 u svojoj kristalnoj modifikaciji A1, koja je naznačena time da ima XRD vrške koji sadrže 14.4°, 15.8°, 17.5°, 19.5°, i 21.9° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
6. Spoj prema bilo kojem zahtjevu od 2 do 5 u svojoj kristalnoj modifikaciji A1, koja je naznačena time da ima slijedeće XRD podatke:
Oblik A1:
[image]
7. Spoj prema zahtjevu 1, naznačen time da je kristalni 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat hidrat.
8. Spoj prema zahtjevu 7, naznačen time da je kristalni 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat dihidrat.
9. Spoj prema zahtjevu 8 u svojoj kristalnoj modifikaciji H1, koja je naznačena time da ima XRD vrške koji sadrže 3.1°, 9.4°, i 18.8° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
10. Spoj prema zahtjevu 8 u svojoj kristalnoj modifikaciji H1, koja je naznačena time da ima XRD vrške koji sadrže 19.1 °, 22.8°, i 26.4° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
11. Spoj prema zahtjevu 8 u svojoj kristalnoj modifikaciji H1, koja je naznačena time da ima XRD vrške koji sadrže 14.4°, 15.0°, i 17.8° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
12. Spoj prema zahtjevu 8 u svojoj kristalnoj modifikaciji H1, koja je naznačena time da ima XRD vrške koji sadrže 14.7°, 18.6°, 23.2°, 23.8°, 26.8°, i 27.6° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
13. Spoj prema bilo kojem zahtjevu od 8 do 12 u svojoj kristalnoj modifikaciji H1, koja je naznačena time da ima slijedeće XRD podatke:
Oblik H1:
[image]
14. 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat u svojoj kristalnoj modifikaciji NF3, koja je naznačena time da ima XRD vrške koji sadrže 15.3°, 16.7°, 21.6°, i 23.1 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
15. Spoj prema zahtjevu 14 u svojoj kristalnoj modifikaciji NF3, koja je naznačena time da ima slijedeće XRD podatke:
Oblik NF3:
[image]
16. Spoj prema zahtjevu 7 u svojoj kristalnoj modifikaciji NF5, koja je naznačena time da ima XRD vrške koji sadrže 13.9°, 15.7°, 16.6°, 17.3°, 19.8°, i 22.1° 2θ (sve ± 0.1° 2θ, korištenjem Cu-Kα1 zračenja).
17. Spoj prema zahtjevu 16 u svojoj kristalnoj modifikaciji NF5, koja je naznačena time da ima slijedeće XRD podatke:
Oblik NF5:
[image]
18. Uporaba barem jednog spoja prema bilo kojem zahtjevu od 1 do 17 naznačena time da je za pripravu medikamenta.
19. Uporaba prema zahtjevu 18 naznačena time da je za liječenje i/ili sprečavanje fizioloških i/ili patofizioloških stanja, koja su uzrokovana, posredovana i/ili šire pomoću inhibicije, regulacije i/ili modulacije signalne transdukcije kinaza, naročito pomoću inhibicije tirozin kinaza, poželjno Met-kinaze.
20. Uporaba prema zahtjevu 18 naznačena time da je za liječenje i/ili sprečavanje fizioloških i/ili patofizioloških stanja koja su odabrana iz skupine koja sadrži: "rak, tumor, maligne tumore, benigne tumore, solidne tumore, sarkome, karcinome, hiperproliferativne poremećaje, karcinoide, Ewingove sarkome, Kaposijeve sarkome, tumore mozga, tumore koji potječu iz mozga i/ili živčanog sustava i/ili meningne tumore, gliome, glioblastome, neuroblastome, rak želuca, rak bubrega, karcinom bubrega, rak prostate, karcinome prostate, tumore vezivnog tkiva, sarkome mekog tkiva, tumore gušterače, tumore jetre, tumore glave, tumore vrata, rak ždrijela, rak jednjaka, rak štitnjače, osteosarkome, retinoblastome, timom, rak testisa, rak pluća, adenokarcinom pluća, karcinom pluća malih stanica, karcinome bronhija, rak dojke, karcinome dojke, rak crijeva, kolorektalne tumore, karcinome debelog crijeva, karcinome rektuma, ginekološke tumore, tumore jajnika, rak maternice, rak grlića maternice, karcinome maternice, karcinome tijela maternice, karcinome korpusa, endometrijske karcinome, rak mokraćnog mjehura, rak urogenitalnog trakta, rak mokraćnog mjehura, rak kože, epitelne tumore, skvamozni epitelni karcinom, bazaliome, spinaliome, melanome, intraokularne melanome, leukemije, monocitnu leukemiju, kroničnu leukemiju, kroničnu mijelocitnu leukemiju, kroničnu limfnu leukemiju, akutnu leukemiju, akutnu mijelocitnu leukemiju, akutnu limfnu leukemiju i/ili limfome".
21. Uporaba prema bilo kojem zahtjevu od 18 do 20, naznačena time da takav medikament sadrži barem jednu dodatnu farmakološki aktivnu tvar.
22. Uporaba prema bilo kojem zahtjevu od 18 do 20, naznačena time da se medikament daje prije i/ili tijekom i/ili nakon tretmana sa barem jednom dodatnom farmakološki aktivnom tvari.
23. Kit naznačen time da sadrži terapeutski učinkovitu količinu barem jednog spoja prema bilo kojem zahtjevu od 1 do 17 i terapeutski učinkovitu količinu barem jedne dodatne farmakološki aktivne tvari koja je različita od spojeva prema bilo kojem zahtjevu od 1 do 17.
24. Postupak za proizvodnju kristalne modifikacije A1 prema bilo kojem zahtjevu od 3 do 6 naznačen time da sadrži korake:
(a) otapanje ili disperziju 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-ona (slobodna baza) ili jedne ili više njegovih soli u otapalu ili smjesi otapala, poželjno u 2-propanolu ili kloroformu, proizvoljno uz miješanje,
(b) konverziju 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-ona (slobodna baza) ili jedne ili više njegovih soli u odgovarajuću sol dihidrogenfosfata uz dodavanje vodene ili etanolne otopine fosforne kiseline, proizvoljno uz miješanje,
(c) miješanje dobivene disperzije iz koraka (b) na sobnoj temperaturi tijekom jednog ili više sati ili dana, poželjno tijekom 1 ili 2 sata,
(d) obnavljanje istaloženog 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata pomoću filtriranja, proizvoljno uz naknadno ispiranje sa otapalom ili smjesom otapala, te proizvoljno uz naknadno sušenje, poželjno in vacuo, proizvoljno kod povišene temperature T, poželjno 30° C do 95° C, poželjnije 70° C.
25. Postupak za proizvodnju kristalne modifikacije A1 prema bilo kojem zahtjevu od 3 do 6 naznačen time da sadrži korake:
(a) disperziju 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-ona (slobodna baza) ili jedne ili više njegovih soli u otapalu ili u smjesi otapala, poželjno u vodi, te dodavanje vodene otopine fosforne kiseline, proizvoljno uz miješanje,
(b) grijanje dobivene disperzije iz koraka (a) do povišene temperature T1, poželjno 30° C do 95° C, poželjnije 50°C, proizvoljno uz miješanje, te hlađenje dobivene otopine, poželjno kod 0° C do 40° C, poželjnije kod 20°C, proizvoljno uz miješanje, prije njenog razrjeđivanja sa otapalom ili smjesom otapala, poželjno sa acetonom, proizvoljno uz miješanje,
(c) miješanje dobivene disperzije iz koraka (b) kod 0° C do 40° C, poželjno kod 10° C, dok se ne okonča kristalizacija i/ili njenim inkubiranjem na sobnoj temperaturi tijekom jednog ili više sati ili dana, proizvoljno uz miješanje,
(d) obnavljanje istaloženog 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata sa filtriranjem, uz proizvoljno hlađenje dobivene disperzije iz koraka (c) kod 0° C do 20° C, poželjno kod 5° C, prije filtriranja, proizvoljno uz miješanje, proizvoljno uz naknadno ispiranje sa otapalom ili smjesom otapala, poželjno sa acetonom, te proizvoljno uz naknadno sušenje, poželjno in vacuo, proizvoljno kod povišene temperature T2, poželjno 30° C do 95° C, poželjnije 70° C,
(e) proizvoljno, vrenje osušenih kristala iz koraka (d) u otapalu ili smjesi otapala, poželjno u etanolu, kao disperzije tijekom jedne ili više minuta, poželjno 30 minuta, te njihovog povrata iz vrele disperzije pomoću filtriranja.
26. Postupak za proizvodnju kristalne modifikacije A1 prema bilo kojem zahtjevu od 3 do 6 naznačen time da sadrži korake:
(a) disperziju 6-(1-metil-1 H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-ona (slobodna baza) ili jedne ili više njegovih soli u smjesi otapala, poželjno u smjesi voda:aceton, te dodavanje vodene otopine fosforne kiseline, proizvoljno uz miješanje,
(b) grijanje dobivene disperzije iz koraka (a) na povišenoj temperaturi T1, poželjno 30° C do 95° C, poželjnije 55°C, proizvoljno uz miješanje, te potom hlađenje dobivene otopine, poželjno na 0° C do 50° C, proizvoljno uz miješanje, uz određenu brzinu hlađenja, poželjno 0.1-1 K/min, poželjnije 0.1-0.3 K/min, proizvoljno uz miješanje, dok ne započne kristalizacija,
(c) daljnje hlađenje dobivene disperzije iz koraka (b) poželjno kod -20° C do 0° C, poželjnije kod -10°C, proizvoljno uz miješanje, uz određenu brzinu hlađenja, poželjno 0.1-1 K/min, poželjnije 0.1-0.3 K/min, proizvoljno uz miješanje,
(d) miješanje dobivene disperzije iz koraka (c) kod -20° C do 40° C, poželjno kod -10° C, dok se ne okonča kristalizacija,
(e) obnavljanje kristaliziranog 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata sa filtriranjem, proizvoljno uz naknadno ispiranje sa otapalom ili smjesom otapala, poželjno acetonom, te proizvoljno uz naknadno sušenje, poželjno in vacuo, proizvoljno kod povišene temperature T2, poželjno kod 30° C do 95° C, poželjnije 70° C.
27. Postupak za proizvodnju kristalne modifikacije H1 prema bilo kojem zahtjevu od 9 do 13 naznačen time da sadrži korake:
(a) raspodjelu 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata kristalne modifikacije A1 na podlogu, poželjno na omeđenu površinu spremnika, poželjnije u Petrijevu zdjelicu, te zatim njegovo inkubiranje u zatvorenom desikatoru iznad vode ili vodene otopine soli tijekom jednog ili više dana ili tjedana.
28. Postupak za proizvodnju kristalne modifikacije H1 prema bilo kojem zahtjevu od 9 do 13 naznačen time da sadrži korake:
(a) disperziju 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata kristalne modifikacije A1 u smjesi dva ili više otapala, poželjno u binarnoj smjesi, gdje su poželjno otapala odabrana iz skupine koja sadrži: "vodu, metanol, etanol, 2-propanol, aceton, TFH i acetonitril", proizvoljno uz miješanje, te uz miješanje dobivene disperzije kod povišene temperature T1, poželjno kod 30° C do 95° C, poželjnije kod 50° C, tijekom jednog ili više dana ili tjedana,
(b) obnavljanje istaloženog 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat dihidrata pomoću filtriranja, proizvoljno uz naknadno ispiranje sa otapalom ili smjesom otapala, te proizvoljno uz naknadno sušenje, poželjno in vacuo, proizvoljno kod povišene temperature T2, poželjno 30° C do 95° C, poželjnije 70° C.
29. Postupak za proizvodnju kristalne modifikacije NF3 prema bilo kojem zahtjevu od 14 do 15, naznačen time da sadrži korake:
(a) disperziju ili otapanje 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata kristalne modifikacije A1 u smjesi dva ili više otapala, poželjno u binarnoj smjesi, gdje su poželjno otapala odabrana iz skupine koja sadrži: "vodu, metanol, etanol, 2-propanol, aceton, TFH, acetonitril i 1,4-dioksan", proizvoljno uz miješanje, te zatim isparavanje smjese dva ili više otapala na sobnoj temperaturi ili povišenoj temperaturi T1, poželjno 30° C do 95° C, poželjnije 50° C, dok ne dođe do kristalizacije,
(b) obnavljanje istaloženog 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat hidrata pomoću filtracije, te proizvoljno sadrži naknadno ispiranje sa otapalom ili smjesom otapala, te proizvoljno naknadno sušenje, poželjno in vacuo, proizvoljno kod povišene temperature T2, poželjno 30° C do 95° C, poželjnije 70° C.
30. Postupak za proizvodnju kristalne modifikacije NF5 prema bilo kojem zahtjevu od 16 do 17, naznačen time da sadrži korake:
(a) otapanje 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfat anhidrata kristalne modifikacije A1 u binarnoj smjesi otapala, poželjno voda:metanol, najpoželjnije u omjeru 1:1 (v:v), te brzog isparavanja smjese otapala kod povišene temperature, poželjno 40-80 °C, najpoželjnije 60 °C, pod vakuumom dok se ne dobije talog,
(b) proizvoljno, dodatnu raspodjelu taloga dobivenog u koraku (a) kao praha na podlogu, poželjno na omeđenu površinu spremnika, poželjnije u Petrijevu zdjelicu, te zatim njeno inkubiranje u zatvorenom desikatoru iznad vode ili vodene otopine soli uz određenu relativnu vlažnost (RH), poželjno 80-100% RH, poželjnije 90-100% RH, tijekom jednog ili više dana ili tjedana.
31. Postupak za proizvodnju kristalne modifikacije NF5 prema bilo kojem zahtjevu od 16 do 17, naznačen time da sadrži korak:
(a) raspodjele 6-(1-metil-1H-pirazol-4-il)-2-{3-[5-(2-morfolin-4-il-etoksi)-pirimidin-2-il]-benzil}-2H-piridazin-3-on dihidrogenfosfata kristalnog oblika NF3 kao praha na podlogu, poželjno na omeđenu površinu spremnika, poželjnije u Petrijevu zdjelicu, te zatim njegovo inkubiranje u zatvorenom desikatoru iznad vode ili vodene otopine soli uz određenu relativnu vlažnost (RH), poželjno 80-100% RH, poželjnije 90-100% RH, tijekom jednog ili više dana ili tjedana.
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Family Cites Families (46)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE19604388A1 (de) | 1996-02-07 | 1997-08-14 | Merck Patent Gmbh | Arylalkyl-diazinone |
| JPH10259176A (ja) | 1997-03-17 | 1998-09-29 | Japan Tobacco Inc | 血管新生阻害作用を有する新規アミド誘導体及びその用途 |
| TWI241295B (en) | 1998-03-02 | 2005-10-11 | Kowa Co | Pyridazine derivative and medicine containing the same as effect component |
| AUPQ462299A0 (en) | 1999-12-13 | 2000-01-13 | Fujisawa Pharmaceutical Co., Ltd. | Pyrazolopyridine compound and pharmaceutical use thereof |
| US6242461B1 (en) | 2000-01-25 | 2001-06-05 | Pfizer Inc. | Use of aryl substituted azabenzimidazoles in the treatment of HIV and AIDS related diseases |
| EP1463509A1 (en) | 2001-10-31 | 2004-10-06 | MERCK PATENT GmbH | Type 4 phosphodiesterase inhibitors and uses thereof |
| CA2510298A1 (en) | 2002-12-20 | 2004-07-15 | Pharmacia Corporation | Acyclic pyrazole compounds |
| CA2530589A1 (en) | 2003-07-02 | 2005-01-20 | Sugen Inc. | Arylmethyl triazolo and imidazopyrazines as c-met inhibitors |
| US7959919B2 (en) | 2003-11-19 | 2011-06-14 | Novelmed Therapeutics, Inc. | Method of inhibiting factor B-mediated complement activation |
| TW200612918A (en) | 2004-07-29 | 2006-05-01 | Threshold Pharmaceuticals Inc | Lonidamine analogs |
| US20070015771A1 (en) | 2004-07-29 | 2007-01-18 | Threshold Pharmaceuticals, Inc. | Lonidamine analogs |
| US20070043057A1 (en) | 2005-02-09 | 2007-02-22 | Threshold Pharmaceuticals, Inc. | Lonidamine analogs |
| WO2007044796A2 (en) | 2005-10-11 | 2007-04-19 | Nps Pharmaceuticals, Inc. | Pyridazinone compounds as calcilytics |
| WO2007064797A2 (en) | 2005-11-30 | 2007-06-07 | Vertex Pharmaceuticals Incorporated | Inhibitors of c-met and uses thereof |
| DE102005057924A1 (de) | 2005-12-05 | 2007-06-06 | Merck Patent Gmbh | Pyridazinonderivate |
| KR101412675B1 (ko) | 2005-12-21 | 2014-07-03 | 얀센 파마슈티카 엔.브이. | 티로신 키나제 모듈레이터로서의 트리아졸로피리다진 |
| WO2007130383A2 (en) | 2006-04-28 | 2007-11-15 | Northwestern University | Compositions and treatments using pyridazine compounds and secretases |
| NL2000613C2 (nl) | 2006-05-11 | 2007-11-20 | Pfizer Prod Inc | Triazoolpyrazinederivaten. |
| PE20080403A1 (es) | 2006-07-14 | 2008-04-25 | Amgen Inc | Derivados heterociclicos fusionados y metodos de uso |
| US7737149B2 (en) | 2006-12-21 | 2010-06-15 | Astrazeneca Ab | N-[5-[2-(3,5-dimethoxyphenyl)ethyl]-2H-pyrazol-3-yl]-4-(3,5-dimethylpiperazin-1-yl)benzamide and salts thereof |
| DE102007026341A1 (de) | 2007-06-06 | 2008-12-11 | Merck Patent Gmbh | Benzoxazolonderivate |
| DE102007032507A1 (de) | 2007-07-12 | 2009-04-02 | Merck Patent Gmbh | Pyridazinonderivate |
| AR068876A1 (es) | 2007-10-16 | 2009-12-09 | Novartis Ag | Heterociclos utiles como modulador de los receptores npy y y2 y composiciones farmaceuticas que los contienen |
| CN101910158A (zh) | 2007-10-25 | 2010-12-08 | 阿斯利康(瑞典)有限公司 | 可用于治疗细胞增殖性病症的吡啶衍生物和吡嗪衍生物 |
| MX2010004705A (es) | 2007-10-31 | 2010-05-27 | Nissan Chemical Ind Ltd | Derivados de piridazinona y uso de los mismos como inhibidores del receptor p2x7. |
| CL2008003407A1 (es) | 2007-11-16 | 2010-01-11 | Boehringer Ingelheim Int | Compuestos derivados de aril- y heteroarilcarbonilo de heterobiciclo sustituido; composicion farmaceutica; procedimiento de preparacion; y su uso en el tratamiento y/o prevencion de trastornos metabolicos, mediado por la inhibicion de la enzima hsd-1. |
| CL2008003785A1 (es) | 2007-12-21 | 2009-10-09 | Du Pont | Compuestos derivados de piridazina; composiciones herbicidas que comprenden a dichos compuestos; y método para controlar el crecimiento de la vegetación indeseada. |
| PL2235012T3 (pl) | 2007-12-21 | 2013-12-31 | Palau Pharma Sa | Pochodne 4-amino-pirymidyny jako antagoniści receptora H<sub>4</sub> histaminowego |
| CL2008003799A1 (es) | 2007-12-21 | 2009-12-18 | Synthon Bv | Composicion farmaceutica que comprende raloxifeno en forma de tableta de liberacion inmediata; util para el tratamiento y/o prevencion de la osteoporosis. |
| PE20091339A1 (es) | 2007-12-21 | 2009-09-26 | Glaxo Group Ltd | Derivados de oxadiazol con actividad sobre receptores s1p1 |
| WO2009080533A1 (en) | 2007-12-21 | 2009-07-02 | F. Hoffmann-La Roche Ag | Heteroaryl derivatives as orexin receptor antagonists |
| US7816540B2 (en) | 2007-12-21 | 2010-10-19 | Hoffmann-La Roche Inc. | Carboxyl- or hydroxyl-substituted benzimidazole derivatives |
| TW200930375A (en) | 2007-12-21 | 2009-07-16 | Exelixis Inc | Benzofuropyrimidinones |
| NZ586913A (en) | 2007-12-21 | 2012-06-29 | Astrazeneca Ab | Bicyclic derivatives for use in the treatment of androgen receptor associated conditions |
| EP2072506A1 (de) | 2007-12-21 | 2009-06-24 | Bayer CropScience AG | Thiazolyloxyphenylamidine oder Thiadiazolyloxyphenylamidine und deren Verwendung als Fungizide |
| GB0725059D0 (en) | 2007-12-21 | 2008-01-30 | Syngenta Participations Ag | Novel pyridazine derivatives |
| KR101610607B1 (ko) | 2007-12-21 | 2016-04-07 | 에프. 호프만-라 로슈 아게 | 헤테로사이클릭 항바이러스 화합물 |
| DE102007061963A1 (de) | 2007-12-21 | 2009-06-25 | Merck Patent Gmbh | Pyridazinonderivate |
| US8202996B2 (en) | 2007-12-21 | 2012-06-19 | Bristol-Myers Squibb Company | Crystalline forms of N-(tert-butoxycarbonyl)-3-methyl-L-valyl-(4R)-4-((7-chloro-4-methoxy-1-isoquinolinyl)oxy)-N- ((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)-L-prolinamide |
| CN101538245B (zh) | 2008-03-18 | 2011-02-16 | 中国科学院上海药物研究所 | 一类哒嗪酮类化合物及其制备方法和制备药物的用途 |
| DE102008019907A1 (de) | 2008-04-21 | 2009-10-22 | Merck Patent Gmbh | Pyridazinonderivate |
| EP2328586A2 (en) | 2008-05-20 | 2011-06-08 | Cephalon, Inc. | Substituted pyridazinone derivatives as histamine-3 (h3) receptor ligands |
| DE102008028905A1 (de) | 2008-06-18 | 2009-12-24 | Merck Patent Gmbh | 3-(3-Pyrimidin-2-yl-benzyl)-[1,2,4]triazolo[4,3-b]pyridazinderivate |
| CA2729993A1 (en) | 2008-07-25 | 2010-01-28 | Boehringer Ingelheim International Gmbh | Synthesis of inhibitors of 11beta-hydroxysteroid dehydrogenase type 1 |
| US20120028988A1 (en) | 2009-03-30 | 2012-02-02 | Sumitomo Chemical Company, Limited | Use of pyridazinone compound for control of harmful arthropod pests |
| AR082590A1 (es) | 2010-08-12 | 2012-12-19 | Hoffmann La Roche | Inhibidores de la tirosina-quinasa de bruton |
-
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