CA2590756C - Stereoselective process and crystalline forms of a camptothecin - Google Patents
Stereoselective process and crystalline forms of a camptothecin Download PDFInfo
- Publication number
- CA2590756C CA2590756C CA2590756A CA2590756A CA2590756C CA 2590756 C CA2590756 C CA 2590756C CA 2590756 A CA2590756 A CA 2590756A CA 2590756 A CA2590756 A CA 2590756A CA 2590756 C CA2590756 C CA 2590756C
- Authority
- CA
- Canada
- Prior art keywords
- camptothecin
- treatment
- process according
- tumor disease
- solvent
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 238000000034 method Methods 0.000 title claims abstract description 29
- 229940127093 camptothecin Drugs 0.000 title claims abstract description 27
- 230000000707 stereoselective effect Effects 0.000 title claims abstract description 11
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 title description 14
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 title description 10
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 title description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 6
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 33
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 21
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 21
- 150000001875 compounds Chemical class 0.000 claims description 20
- 239000000203 mixture Substances 0.000 claims description 18
- 239000003814 drug Substances 0.000 claims description 17
- 239000006184 cosolvent Substances 0.000 claims description 15
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 14
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
- XKIDBQHJMYSFPX-NRFANRHFSA-N 80758-83-4 Chemical compound C1=CC=C2C(C=O)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 XKIDBQHJMYSFPX-NRFANRHFSA-N 0.000 claims description 11
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 10
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 9
- 238000002441 X-ray diffraction Methods 0.000 claims description 9
- 238000002360 preparation method Methods 0.000 claims description 9
- 150000001241 acetals Chemical class 0.000 claims description 8
- VFWCMGCRMGJXDK-UHFFFAOYSA-N 1-chlorobutane Chemical compound CCCCCl VFWCMGCRMGJXDK-UHFFFAOYSA-N 0.000 claims description 7
- 239000011541 reaction mixture Substances 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 150000007529 inorganic bases Chemical class 0.000 claims description 5
- 239000002244 precipitate Substances 0.000 claims description 5
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 230000002378 acidificating effect Effects 0.000 claims description 3
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 150000007530 organic bases Chemical class 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims 2
- ZBDXGNXNXXPKJI-UHFFFAOYSA-N o-tert-butylhydroxylamine;hydrochloride Chemical compound Cl.CC(C)(C)ON ZBDXGNXNXXPKJI-UHFFFAOYSA-N 0.000 claims 2
- 239000002775 capsule Substances 0.000 claims 1
- 239000007795 chemical reaction product Substances 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 239000012429 reaction media Substances 0.000 claims 1
- UIVFUQKYVFCEKJ-OPTOVBNMSA-N gimatecan Chemical compound C1=CC=C2C(\C=N\OC(C)(C)C)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UIVFUQKYVFCEKJ-OPTOVBNMSA-N 0.000 abstract description 25
- 229950009073 gimatecan Drugs 0.000 abstract description 23
- 239000011877 solvent mixture Substances 0.000 abstract description 4
- 238000004090 dissolution Methods 0.000 abstract description 3
- 238000001556 precipitation Methods 0.000 abstract description 3
- 239000000843 powder Substances 0.000 description 10
- 229940079593 drug Drugs 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 230000000259 anti-tumor effect Effects 0.000 description 5
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 238000011097 chromatography purification Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 4
- 239000000047 product Substances 0.000 description 4
- 238000010992 reflux Methods 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 239000004480 active ingredient Substances 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 238000002425 crystallisation Methods 0.000 description 3
- 230000008025 crystallization Effects 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 150000002923 oximes Chemical class 0.000 description 3
- 238000000634 powder X-ray diffraction Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 230000001225 therapeutic effect Effects 0.000 description 3
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 description 3
- 229960000303 topotecan Drugs 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical compound COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 description 2
- -1 5-tetrazolyl Chemical group 0.000 description 2
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 description 2
- 230000001028 anti-proliverative effect Effects 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 230000001472 cytotoxic effect Effects 0.000 description 2
- 231100000135 cytotoxicity Toxicity 0.000 description 2
- 230000003013 cytotoxicity Effects 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 description 2
- 208000037841 lung tumor Diseases 0.000 description 2
- 230000014759 maintenance of location Effects 0.000 description 2
- 150000002894 organic compounds Chemical class 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 231100001274 therapeutic index Toxicity 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- FBDOJYYTMIHHDH-OZBJMMHXSA-N (19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-2,4,6,8,10,14,20-heptaen-18-one Chemical compound CC[C@@]1(O)C(=O)OCC2=CN3Cc4cc5ccccc5nc4C3C=C12 FBDOJYYTMIHHDH-OZBJMMHXSA-N 0.000 description 1
- 206010065553 Bone marrow failure Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 206010011793 Cystitis haemorrhagic Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 1
- 206010059024 Gastrointestinal toxicity Diseases 0.000 description 1
- 206010018338 Glioma Diseases 0.000 description 1
- 238000004566 IR spectroscopy Methods 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- 208000007093 Leukemia L1210 Diseases 0.000 description 1
- 206010058467 Lung neoplasm malignant Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 241000209018 Nyssaceae Species 0.000 description 1
- 206010041067 Small cell lung cancer Diseases 0.000 description 1
- HPDRGGNSEBLDKL-NRFANRHFSA-N ac1l3zgz Chemical compound C1=CC=C2C(CO)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HPDRGGNSEBLDKL-NRFANRHFSA-N 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 125000003158 alcohol group Chemical group 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000005111 carboxyalkoxy group Chemical group 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000029742 colonic neoplasm Diseases 0.000 description 1
- 231100000433 cytotoxic Toxicity 0.000 description 1
- 231100000050 cytotoxic potential Toxicity 0.000 description 1
- 238000002050 diffraction method Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 231100000414 gastrointestinal toxicity Toxicity 0.000 description 1
- 229910002804 graphite Inorganic materials 0.000 description 1
- 239000010439 graphite Substances 0.000 description 1
- 201000002802 hemorrhagic cystitis Diseases 0.000 description 1
- 231100000086 high toxicity Toxicity 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 229960004768 irinotecan Drugs 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 201000002364 leukopenia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 201000005296 lung carcinoma Diseases 0.000 description 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 239000008188 pellet Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 210000002307 prostate Anatomy 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 206010043554 thrombocytopenia Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- 210000004881 tumor cell Anatomy 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 210000004916 vomit Anatomy 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/12—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains three hetero rings
- C07D491/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/22—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains four or more hetero rings
-
- 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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hematology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP04030246 | 2004-12-21 | ||
| EP04030246.5 | 2004-12-21 | ||
| PCT/EP2005/056849 WO2006067092A2 (en) | 2004-12-21 | 2005-12-16 | Stereoselective process and crystalline forms of a camptothecin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CA2590756A1 CA2590756A1 (en) | 2006-06-29 |
| CA2590756C true CA2590756C (en) | 2014-09-02 |
Family
ID=34927884
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2590756A Expired - Fee Related CA2590756C (en) | 2004-12-21 | 2005-12-16 | Stereoselective process and crystalline forms of a camptothecin |
Country Status (18)
| Country | Link |
|---|---|
| US (3) | US7799921B2 (enExample) |
| EP (1) | EP1828196B1 (enExample) |
| JP (2) | JP5491699B2 (enExample) |
| KR (1) | KR101355121B1 (enExample) |
| CN (1) | CN101084221B (enExample) |
| AU (1) | AU2005318227B2 (enExample) |
| BR (1) | BRPI0515832A (enExample) |
| CA (1) | CA2590756C (enExample) |
| CY (1) | CY1117243T1 (enExample) |
| DK (1) | DK1828196T3 (enExample) |
| ES (1) | ES2395930T3 (enExample) |
| HR (1) | HRP20120926T1 (enExample) |
| ME (1) | ME01495B (enExample) |
| PL (1) | PL1828196T3 (enExample) |
| PT (1) | PT1828196E (enExample) |
| RS (1) | RS52585B (enExample) |
| SI (1) | SI1828196T1 (enExample) |
| WO (1) | WO2006067092A2 (enExample) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1828196B1 (en) * | 2004-12-21 | 2012-10-17 | SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. | Stereoselective process and crystalline forms of a camptothecin |
| ITRM20050418A1 (it) * | 2005-08-04 | 2007-02-05 | Sigma Tau Ind Farmaceuti | Sistemi terapeutici a rilascio immediato per il migliorato assorbimento orale di 7-[(e)-t-butilossimminometil] camptotecina. |
| FR2938534B1 (fr) | 2008-11-14 | 2012-10-26 | Sanofi Aventis | Procede de preparation de l'hemifumarate d'eplivanserine |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH03271278A (ja) * | 1990-03-16 | 1991-12-03 | Nissan Chem Ind Ltd | ２―アニリノピリミジン誘導体および農園芸用殺菌剤 |
| JP3046401B2 (ja) * | 1991-06-18 | 2000-05-29 | イハラケミカル工業株式会社 | ６−〔１−（ｎ−アルコキシイミノ）エチル〕サリチル酸誘導体及びその製造法 |
| IL106786A (en) * | 1992-09-10 | 1997-02-18 | Basf Ag | Substituted pyridine derivatives and fungicidal compositions containing them |
| EP1044977B1 (en) * | 1999-03-09 | 2002-05-02 | Sigma-Tau Industrie Farmaceutiche Riunite S.p.A. | Camptothecin derivatives having antitumor activity |
| AU2003215594A1 (en) * | 2002-03-01 | 2003-09-16 | Pharmacia Italia S.P.A. | Crystalline polymorphic form of irinotecan hydrochloride |
| EP1828196B1 (en) * | 2004-12-21 | 2012-10-17 | SIGMA-TAU Industrie Farmaceutiche Riunite S.p.A. | Stereoselective process and crystalline forms of a camptothecin |
-
2005
- 2005-12-16 EP EP05849781A patent/EP1828196B1/en not_active Expired - Lifetime
- 2005-12-16 HR HRP20120926TT patent/HRP20120926T1/hr unknown
- 2005-12-16 ME MEP-2012-128A patent/ME01495B/me unknown
- 2005-12-16 PT PT05849781T patent/PT1828196E/pt unknown
- 2005-12-16 DK DK05849781.9T patent/DK1828196T3/da active
- 2005-12-16 CA CA2590756A patent/CA2590756C/en not_active Expired - Fee Related
- 2005-12-16 ES ES05849781T patent/ES2395930T3/es not_active Expired - Lifetime
- 2005-12-16 KR KR1020077016814A patent/KR101355121B1/ko not_active Expired - Fee Related
- 2005-12-16 PL PL05849781T patent/PL1828196T3/pl unknown
- 2005-12-16 SI SI200531610T patent/SI1828196T1/sl unknown
- 2005-12-16 AU AU2005318227A patent/AU2005318227B2/en not_active Ceased
- 2005-12-16 CN CN2005800440829A patent/CN101084221B/zh not_active Expired - Lifetime
- 2005-12-16 WO PCT/EP2005/056849 patent/WO2006067092A2/en not_active Ceased
- 2005-12-16 RS RS20120505A patent/RS52585B/sr unknown
- 2005-12-16 US US11/721,282 patent/US7799921B2/en not_active Expired - Fee Related
- 2005-12-16 JP JP2007547467A patent/JP5491699B2/ja not_active Expired - Fee Related
- 2005-12-16 BR BRPI0515832-0A patent/BRPI0515832A/pt not_active Application Discontinuation
-
2010
- 2010-08-17 US US12/857,743 patent/US8124769B2/en not_active Expired - Fee Related
- 2010-08-17 US US12/857,776 patent/US8101758B2/en not_active Expired - Fee Related
-
2012
- 2012-10-30 CY CY20121101034T patent/CY1117243T1/el unknown
- 2012-11-09 JP JP2012247587A patent/JP5982261B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| US20100311783A1 (en) | 2010-12-09 |
| HK1113487A1 (en) | 2008-10-03 |
| WO2006067092A3 (en) | 2006-11-02 |
| EP1828196A2 (en) | 2007-09-05 |
| RS52585B (sr) | 2013-04-30 |
| US7799921B2 (en) | 2010-09-21 |
| CN101084221B (zh) | 2011-05-11 |
| PL1828196T3 (pl) | 2013-02-28 |
| AU2005318227A1 (en) | 2006-06-29 |
| EP1828196B1 (en) | 2012-10-17 |
| ES2395930T3 (es) | 2013-02-18 |
| KR101355121B1 (ko) | 2014-01-24 |
| JP5982261B2 (ja) | 2016-08-31 |
| CN101084221A (zh) | 2007-12-05 |
| US8124769B2 (en) | 2012-02-28 |
| PT1828196E (pt) | 2012-11-19 |
| KR20070097535A (ko) | 2007-10-04 |
| CY1117243T1 (el) | 2017-04-05 |
| US20090239893A1 (en) | 2009-09-24 |
| JP2013067629A (ja) | 2013-04-18 |
| ME01495B (me) | 2014-04-20 |
| DK1828196T3 (da) | 2012-11-26 |
| BRPI0515832A (pt) | 2008-08-05 |
| US20100311784A1 (en) | 2010-12-09 |
| JP5491699B2 (ja) | 2014-05-14 |
| JP2008524306A (ja) | 2008-07-10 |
| CA2590756A1 (en) | 2006-06-29 |
| WO2006067092A2 (en) | 2006-06-29 |
| HRP20120926T1 (hr) | 2012-12-31 |
| SI1828196T1 (sl) | 2012-12-31 |
| AU2005318227B2 (en) | 2011-08-18 |
| US8101758B2 (en) | 2012-01-24 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CA2262745C (en) | Highly lipophilic camptothecin derivatives | |
| CN116583526B (zh) | 新型喜树碱衍生物、含其的组合物和其用途 | |
| CN103880839B (zh) | 13a-(S)去氧娃儿藤宁衍生物、其药物组合物与用途 | |
| JP2025526425A (ja) | 抗体薬物複合体に適した毒素分子 | |
| CN102649765B (zh) | 具有抗白血病活性的大黄素二正辛基季铵盐及其制备方法 | |
| US8124769B2 (en) | Stereoselective process and crystalline forms of a camptothecin | |
| CN116253747A (zh) | 新型高喜树碱衍生物、含其的组合物和其用途 | |
| CN110156817B (zh) | 双吴茱萸碱分子抗肿瘤衍生物及其制备与应用 | |
| DK2044080T3 (en) | Camptothecin derivatives with antitumor activity | |
| MX2007007258A (en) | Stereoselective process and crystalline forms of a camptothecin | |
| KR20080068052A (ko) | 신규의 결정형 | |
| HK1113487B (en) | Stereoselective process and crystalline forms of a camptothecin | |
| PL188075B1 (pl) | Rozpuszczalne w wodzie C-pierścieniowe analogi 20(S)-kamptotecyny, kompozycja farmaceutyczna zawierająca te związki, ich zastosowanie oraz sposób wytwarzania | |
| CS159092A3 (en) | Chemical modification 2''-amino group of elsamycin a |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| EEER | Examination request | ||
| MKLA | Lapsed |
Effective date: 20201216 |