CZ51593A3 - Water-soluble analogs of camptothecine, process of their preparation and use - Google Patents
Water-soluble analogs of camptothecine, process of their preparation and use Download PDFInfo
- Publication number
- CZ51593A3 CZ51593A3 CS93515A CS5159391A CZ51593A3 CZ 51593 A3 CZ51593 A3 CZ 51593A3 CS 93515 A CS93515 A CS 93515A CS 5159391 A CS5159391 A CS 5159391A CZ 51593 A3 CZ51593 A3 CZ 51593A3
- Authority
- CZ
- Czechia
- Prior art keywords
- compound
- camptothecin
- formula
- hydrogen
- liquid
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 142
- 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 claims abstract description 103
- 230000008569 process Effects 0.000 title claims abstract description 66
- 238000002360 preparation method Methods 0.000 title abstract description 50
- 150000001875 compounds Chemical class 0.000 claims abstract description 144
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 36
- 210000004881 tumor cell Anatomy 0.000 claims abstract description 8
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 7
- 230000004614 tumor growth Effects 0.000 claims abstract description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 132
- 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 claims description 120
- 229940127093 camptothecin Drugs 0.000 claims description 92
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 85
- 239000007788 liquid Substances 0.000 claims description 63
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 54
- 229910052739 hydrogen Inorganic materials 0.000 claims description 54
- 239000001257 hydrogen Substances 0.000 claims description 54
- 239000000047 product Substances 0.000 claims description 48
- 150000003839 salts Chemical class 0.000 claims description 44
- 238000005984 hydrogenation reaction Methods 0.000 claims description 43
- 238000006243 chemical reaction Methods 0.000 claims description 41
- 239000002904 solvent Substances 0.000 claims description 41
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 40
- 239000000725 suspension Substances 0.000 claims description 39
- 239000003054 catalyst Substances 0.000 claims description 38
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 37
- -1 iodosobenzene ester Chemical class 0.000 claims description 37
- 239000000203 mixture Substances 0.000 claims description 37
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims description 36
- HAWSQZCWOQZXHI-UHFFFAOYSA-N CPT-OH Natural products C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-UHFFFAOYSA-N 0.000 claims description 35
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 33
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 229910052757 nitrogen Inorganic materials 0.000 claims description 27
- 239000007800 oxidant agent Substances 0.000 claims description 27
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical group [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 25
- 239000012429 reaction media Substances 0.000 claims description 24
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 21
- 238000001914 filtration Methods 0.000 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
- 239000012535 impurity Substances 0.000 claims description 18
- 239000007858 starting material Substances 0.000 claims description 18
- 238000000746 purification Methods 0.000 claims description 16
- 229910052697 platinum Inorganic materials 0.000 claims description 14
- 238000001953 recrystallisation Methods 0.000 claims description 12
- ZBIKORITPGTTGI-UHFFFAOYSA-N [acetyloxy(phenyl)-$l^{3}-iodanyl] acetate Chemical compound CC(=O)OI(OC(C)=O)C1=CC=CC=C1 ZBIKORITPGTTGI-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 9
- 125000003277 amino group Chemical group 0.000 claims description 9
- 125000004185 ester group Chemical group 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- 239000002244 precipitate Substances 0.000 claims description 9
- YSAMJAXLRIUOHA-SFVMKZFCSA-N (19S)-19-ethyl-19-hydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),4,6,8,15(20)-pentaene-14,18-dione Chemical compound N1C2=CC=CC=C2CC(CN2C3=O)C1C2=CC1=C3COC(=O)[C@]1(O)CC YSAMJAXLRIUOHA-SFVMKZFCSA-N 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- 125000002837 carbocyclic group Chemical group 0.000 claims description 8
- 238000004090 dissolution Methods 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- JYJVVHFRSFVEJM-UHFFFAOYSA-N iodosobenzene Chemical compound O=IC1=CC=CC=C1 JYJVVHFRSFVEJM-UHFFFAOYSA-N 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 229930013930 alkaloid Natural products 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 5
- 230000000979 retarding effect Effects 0.000 claims description 5
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
- 241001465754 Metazoa Species 0.000 claims description 4
- 125000001931 aliphatic group Chemical group 0.000 claims description 4
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 4
- 150000008280 chlorinated hydrocarbons Chemical class 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000002574 poison Substances 0.000 claims description 4
- 231100000614 poison Toxicity 0.000 claims description 4
- 150000003573 thiols Chemical class 0.000 claims description 4
- MLIWQXBKMZNZNF-KUHOPJCQSA-N (2e)-2,6-bis[(4-azidophenyl)methylidene]-4-methylcyclohexan-1-one Chemical compound O=C1\C(=C\C=2C=CC(=CC=2)N=[N+]=[N-])CC(C)CC1=CC1=CC=C(N=[N+]=[N-])C=C1 MLIWQXBKMZNZNF-KUHOPJCQSA-N 0.000 claims description 3
- 241000759909 Camptotheca Species 0.000 claims description 3
- 241000196324 Embryophyta Species 0.000 claims description 3
- 241000060390 Nothapodytes nimmoniana Species 0.000 claims description 3
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 3
- YCOXTKKNXUZSKD-UHFFFAOYSA-N as-o-xylenol Natural products CC1=CC=C(O)C=C1C YCOXTKKNXUZSKD-UHFFFAOYSA-N 0.000 claims description 3
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- 229910000510 noble metal Inorganic materials 0.000 claims description 3
- 230000001590 oxidative effect Effects 0.000 claims description 3
- USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical group [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 claims description 3
- 150000003464 sulfur compounds Chemical group 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 239000004215 Carbon black (E152) Substances 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
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- LRIUKPUCKCECPT-UHFFFAOYSA-N [hydroxy(phenyl)-$l^{3}-iodanyl] 4-methylbenzenesulfonate Chemical compound C1=CC(C)=CC=C1S(=O)(=O)OI(O)C1=CC=CC=C1 LRIUKPUCKCECPT-UHFFFAOYSA-N 0.000 claims description 2
- 229930195733 hydrocarbon Natural products 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- SNHMUERNLJLMHN-IDEBNGHGSA-N iodobenzene Chemical group I[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 SNHMUERNLJLMHN-IDEBNGHGSA-N 0.000 claims 1
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- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
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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
- C07D491/22—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
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Processing And Handling Of Plastics And Other Materials For Molding In General (AREA)
- Auxiliary Devices For And Details Of Packaging Control (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Fodder In General (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Steroid Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US58964390A | 1990-09-28 | 1990-09-28 | |
| PCT/US1991/006888 WO1992005785A1 (en) | 1990-09-28 | 1991-09-23 | Water soluble camptothecin analogues, processes and methods |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ51593A3 true CZ51593A3 (en) | 1994-01-19 |
Family
ID=24358879
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CS93515A CZ51593A3 (en) | 1990-09-28 | 1991-09-23 | Water-soluble analogs of camptothecine, process of their preparation and use |
Country Status (24)
| Country | Link |
|---|---|
| US (1) | US5734056A (Direct) |
| EP (1) | EP0547165B1 (Direct) |
| JP (1) | JP2848958B2 (Direct) |
| CN (1) | CN1033509C (Direct) |
| AT (1) | ATE186461T1 (Direct) |
| AU (1) | AU664830B2 (Direct) |
| CA (1) | CA2090967C (Direct) |
| CZ (1) | CZ51593A3 (Direct) |
| DE (1) | DE69131775T2 (Direct) |
| DK (1) | DK0547165T3 (Direct) |
| ES (1) | ES2137932T3 (Direct) |
| FI (1) | FI931384A0 (Direct) |
| GR (1) | GR3031823T3 (Direct) |
| HU (1) | HUT70024A (Direct) |
| IE (1) | IE913402A1 (Direct) |
| IL (1) | IL99571A (Direct) |
| NO (1) | NO931153L (Direct) |
| NZ (1) | NZ239947A (Direct) |
| PT (1) | PT99109B (Direct) |
| SI (1) | SI9111599A (Direct) |
| SK (1) | SK283693B6 (Direct) |
| WO (1) | WO1992005785A1 (Direct) |
| YU (1) | YU159991A (Direct) |
| ZA (1) | ZA917748B (Direct) |
Families Citing this family (59)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AP9300587A0 (en) * | 1992-11-12 | 1995-05-05 | Glaxo Inc | Water soluble camptothecin derivatives. |
| US5527913A (en) * | 1993-02-25 | 1996-06-18 | The Stehlin Foundation For Cancer Research | Methods for purifying camptothecin compounds |
| US5880131A (en) * | 1993-10-20 | 1999-03-09 | Enzon, Inc. | High molecular weight polymer-based prodrugs |
| US5447936A (en) * | 1993-12-22 | 1995-09-05 | Bionumerik Pharmaceuticals, Inc. | Lactone stable formulation of 10-hydroxy 7-ethyl camptothecin and methods for uses thereof |
| GB9402934D0 (en) * | 1994-02-16 | 1994-04-06 | Erba Carlo Spa | Camptothecin derivatives and process for their preparation |
| KR960029336A (ko) * | 1995-01-09 | 1996-08-17 | 김충환 | 캄토테신 유도체, 그의 제조 방법 및 이를 함유하는 항암제 |
| US5726181A (en) * | 1995-06-05 | 1998-03-10 | Bionumerik Pharmaceuticals, Inc. | Formulations and compositions of poorly water soluble camptothecin derivatives |
| JPH08333370A (ja) * | 1995-06-08 | 1996-12-17 | Kyorin Pharmaceut Co Ltd | 水に可溶な新規フルオロエチルカンプトテシン誘導体、及びその製造方法 |
| AU7732996A (en) * | 1995-11-22 | 1997-06-11 | Research Triangle Institute | Camptothecin compounds with combined topoisomerase i inhibition and dna alkylation properties |
| US5731316A (en) | 1996-01-30 | 1998-03-24 | The Stehlin Foundation For Cancer Research | Derivatives of camptothecin and methods of treating cancer using these derivatives |
| US6096336A (en) * | 1996-01-30 | 2000-08-01 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| US6407118B1 (en) | 1996-01-30 | 2002-06-18 | The Stehlin Foundation For Cancer Research | Derivatives of camptothecin and methods of treating cancer using these derivatives |
| GB9601779D0 (en) * | 1996-01-30 | 1996-04-03 | Pharmacia Spa | 9, 10 Disubstituted camptothecin derivatives |
| US6043367A (en) * | 1998-09-30 | 2000-03-28 | Roffler; Steve | Proactive antitumor compounds |
| US6228855B1 (en) | 1999-08-03 | 2001-05-08 | The Stehlin Foundation For Cancer Research | Aromatic esters of camptothecins and methods to treat cancers |
| US6352996B1 (en) | 1999-08-03 | 2002-03-05 | The Stehlin Foundation For Cancer Research | Liposomal prodrugs comprising derivatives of camptothecin and methods of treating cancer using these prodrugs |
| EP2289549A3 (en) | 1999-10-01 | 2011-06-15 | Immunogen, Inc. | Immunoconjugates for treating cancer |
| WO2004055020A1 (en) * | 2002-12-16 | 2004-07-01 | Council Of Scientific And Industrial Research | Process for the direct preparation of 5-alkoxy and 5-acyloxy analogues of campthothecins or mappicene ketones |
| AU2003223109A1 (en) * | 2003-03-31 | 2004-10-25 | Council Of Scientific And Industrial Research | Process for preparing topotecan from 10-hydroxy-4-(s) camptothecin |
| WO2004100897A2 (en) | 2003-05-12 | 2004-11-25 | Scinopharm Taiwan, Ltd. | Process for the preparation of 7-alkyl-10-hydroxy-20(s)-camptothecin |
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| JPS5842192B2 (ja) * | 1974-05-18 | 1983-09-17 | フセソユ−ズヌイ ナウチノ イスレドワ−チエレスキ− ヒミコ フアルマツエフチチエスキ− インスチツ−ト イメ−ニ エス オルジヨニキ−ゼ | ５− オキシ −６− アミノメチルベンゾフランノ ユウドウタイノ セイホウ |
| US4473692A (en) * | 1981-09-04 | 1984-09-25 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives and process for preparing same |
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| JPS5946284A (ja) * | 1982-09-10 | 1984-03-15 | Yakult Honsha Co Ltd | １１−ニトロカンプトテシン誘導体およびその製造法 |
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| US4981968A (en) * | 1987-03-31 | 1991-01-01 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| US4943579A (en) * | 1987-10-06 | 1990-07-24 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Water soluble prodrugs of camptothecin |
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| GB9008605D0 (en) * | 1990-04-17 | 1990-06-13 | Smith Kline French Lab | Process |
| HU213136B (en) * | 1990-08-14 | 1997-02-28 | Kyorin Seiyaku Kk | Process for producing fluoroethyl camptothecin derivatives and pharmaceutical compositions containing them |
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-
1991
- 1991-09-23 CZ CS93515A patent/CZ51593A3/cs unknown
- 1991-09-23 FI FI931384A patent/FI931384A0/fi not_active Application Discontinuation
- 1991-09-23 SK SK259-93A patent/SK283693B6/sk not_active IP Right Cessation
- 1991-09-23 HU HU9300878A patent/HUT70024A/hu unknown
- 1991-09-23 JP JP3516992A patent/JP2848958B2/ja not_active Expired - Lifetime
- 1991-09-23 CA CA002090967A patent/CA2090967C/en not_active Expired - Lifetime
- 1991-09-23 WO PCT/US1991/006888 patent/WO1992005785A1/en not_active Ceased
- 1991-09-23 ES ES91918278T patent/ES2137932T3/es not_active Expired - Lifetime
- 1991-09-23 EP EP91918278A patent/EP0547165B1/en not_active Expired - Lifetime
- 1991-09-23 DK DK91918278T patent/DK0547165T3/da active
- 1991-09-23 AU AU87399/91A patent/AU664830B2/en not_active Expired
- 1991-09-23 DE DE69131775T patent/DE69131775T2/de not_active Expired - Lifetime
- 1991-09-23 AT AT91918278T patent/ATE186461T1/de not_active IP Right Cessation
- 1991-09-26 IL IL9957191A patent/IL99571A/xx not_active IP Right Cessation
- 1991-09-26 NZ NZ23994791A patent/NZ239947A/en not_active IP Right Cessation
- 1991-09-27 ZA ZA917748A patent/ZA917748B/xx unknown
- 1991-09-27 PT PT99109A patent/PT99109B/pt not_active IP Right Cessation
- 1991-09-27 IE IE340291A patent/IE913402A1/en not_active IP Right Cessation
- 1991-09-28 CN CN91110656A patent/CN1033509C/zh not_active Expired - Lifetime
- 1991-09-30 YU YU159991A patent/YU159991A/sh unknown
- 1991-09-30 SI SI9111599A patent/SI9111599A/sl unknown
-
1993
- 1993-03-26 NO NO93931153A patent/NO931153L/no unknown
-
1995
- 1995-05-25 US US08/451,079 patent/US5734056A/en not_active Expired - Lifetime
-
1999
- 1999-11-11 GR GR990402820T patent/GR3031823T3/el unknown
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