NO302073B1 - Vannopplöselige camptothecin-derivater - Google Patents
Vannopplöselige camptothecin-derivater Download PDFInfo
- Publication number
- NO302073B1 NO302073B1 NO924158A NO924158A NO302073B1 NO 302073 B1 NO302073 B1 NO 302073B1 NO 924158 A NO924158 A NO 924158A NO 924158 A NO924158 A NO 924158A NO 302073 B1 NO302073 B1 NO 302073B1
- Authority
- NO
- Norway
- Prior art keywords
- camptothecin
- ethylenedioxy
- alkyl
- compound
- methylenedioxy
- Prior art date
Links
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical class 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 22
- 150000001875 compounds Chemical class 0.000 claims description 151
- 229940127093 camptothecin Drugs 0.000 claims description 68
- 206010028980 Neoplasm Diseases 0.000 claims description 38
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 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 29
- 150000003839 salts Chemical class 0.000 claims description 27
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 239000001257 hydrogen Substances 0.000 claims description 23
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 20
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 16
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 12
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 12
- 229910052757 nitrogen Inorganic materials 0.000 claims description 12
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- HONIICLYMWZJFZ-UHFFFAOYSA-N azetidine Chemical compound C1CNC1 HONIICLYMWZJFZ-UHFFFAOYSA-N 0.000 claims description 7
- 239000012453 solvate Substances 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 6
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 6
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 5
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004429 atom Chemical group 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 3
- CIISBYKBBMFLEZ-UHFFFAOYSA-N 1,2-oxazolidine Chemical compound C1CNOC1 CIISBYKBBMFLEZ-UHFFFAOYSA-N 0.000 claims description 2
- CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical compound C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims description 2
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-N 0.000 claims description 2
- FQUYSHZXSKYCSY-UHFFFAOYSA-N 1,4-diazepane Chemical compound C1CNCCNC1 FQUYSHZXSKYCSY-UHFFFAOYSA-N 0.000 claims description 2
- FXHRAKUEZPSMLJ-UHFFFAOYSA-N 1-methyl-1,4-diazepane Chemical compound CN1CCCNCC1 FXHRAKUEZPSMLJ-UHFFFAOYSA-N 0.000 claims description 2
- NOWKCMXCCJGMRR-UHFFFAOYSA-N Aziridine Chemical compound C1CN1 NOWKCMXCCJGMRR-UHFFFAOYSA-N 0.000 claims description 2
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 claims description 2
- ZSIQJIWKELUFRJ-UHFFFAOYSA-N azepane Chemical compound C1CCCNCC1 ZSIQJIWKELUFRJ-UHFFFAOYSA-N 0.000 claims description 2
- USPWKWBDZOARPV-UHFFFAOYSA-N pyrazolidine Chemical compound C1CNNC1 USPWKWBDZOARPV-UHFFFAOYSA-N 0.000 claims description 2
- RVFGKBWWUQOIOU-NDEPHWFRSA-N lurtotecan Chemical group O=C([C@]1(O)CC)OCC(C(N2CC3=4)=O)=C1C=C2C3=NC1=CC=2OCCOC=2C=C1C=4CN1CCN(C)CC1 RVFGKBWWUQOIOU-NDEPHWFRSA-N 0.000 claims 1
- 238000000034 method Methods 0.000 description 57
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 42
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 40
- 238000001819 mass spectrum Methods 0.000 description 30
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 24
- -1 palmoate Chemical compound 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 23
- 239000007787 solid Substances 0.000 description 21
- 238000002360 preparation method Methods 0.000 description 19
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 18
- 239000000203 mixture Substances 0.000 description 18
- 239000000243 solution Substances 0.000 description 17
- 238000006243 chemical reaction Methods 0.000 description 16
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 150000002576 ketones Chemical class 0.000 description 13
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 235000019439 ethyl acetate Nutrition 0.000 description 12
- 239000002904 solvent Substances 0.000 description 11
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- 239000002585 base Substances 0.000 description 10
- 239000002253 acid Substances 0.000 description 9
- 230000000259 anti-tumor effect Effects 0.000 description 8
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 8
- 201000011510 cancer Diseases 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
- 239000000654 additive Substances 0.000 description 6
- 239000002246 antineoplastic agent Substances 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- PRSCCOTYRGOTJG-UHFFFAOYSA-N 1-(6-amino-1,3-benzodioxol-5-yl)-2-chloroethanone Chemical compound C1=C(C(=O)CCl)C(N)=CC2=C1OCO2 PRSCCOTYRGOTJG-UHFFFAOYSA-N 0.000 description 5
- 102000003915 DNA Topoisomerases Human genes 0.000 description 5
- 108090000323 DNA Topoisomerases Proteins 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 5
- 101710183280 Topoisomerase Proteins 0.000 description 5
- 238000007796 conventional method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000007429 general method Methods 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000003795 chemical substances by application Substances 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- CGLCDOZYDURWIG-UHFFFAOYSA-N n-(1,3-benzodioxol-5-yl)acetamide Chemical compound CC(=O)NC1=CC=C2OCOC2=C1 CGLCDOZYDURWIG-UHFFFAOYSA-N 0.000 description 4
- 238000011580 nude mouse model Methods 0.000 description 4
- 238000007911 parenteral administration Methods 0.000 description 4
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- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- 238000010898 silica gel chromatography Methods 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 4
- XGNXYCFREOZBOL-UHFFFAOYSA-N 1,3-benzodioxol-5-amine Chemical compound NC1=CC=C2OCOC2=C1 XGNXYCFREOZBOL-UHFFFAOYSA-N 0.000 description 3
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- 241000699660 Mus musculus Species 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- FGIXZILUSHAOJP-QFIPXVFZSA-N ac1lahqq Chemical compound C1=C2C(CCl)=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=CC2=C1OCO2 FGIXZILUSHAOJP-QFIPXVFZSA-N 0.000 description 3
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 3
- 239000012346 acetyl chloride Substances 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 125000003710 aryl alkyl group Chemical group 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
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- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 3
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- 208000032839 leukemia Diseases 0.000 description 3
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- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
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- 238000005086 pumping Methods 0.000 description 3
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- IWZSHWBGHQBIML-ZGGLMWTQSA-N (3S,8S,10R,13S,14S,17S)-17-isoquinolin-7-yl-N,N,10,13-tetramethyl-2,3,4,7,8,9,11,12,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3-amine Chemical compound CN(C)[C@H]1CC[C@]2(C)C3CC[C@@]4(C)[C@@H](CC[C@@H]4c4ccc5ccncc5c4)[C@@H]3CC=C2C1 IWZSHWBGHQBIML-ZGGLMWTQSA-N 0.000 description 2
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- BZKOZYWGZKRTIB-UHFFFAOYSA-N 2,3-dihydro-1,4-benzodioxin-6-amine Chemical compound O1CCOC2=CC(N)=CC=C21 BZKOZYWGZKRTIB-UHFFFAOYSA-N 0.000 description 2
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
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- CSZGVPCUMJDPAB-UHFFFAOYSA-N n-[6-(2-chloroacetyl)-1,3-benzodioxol-5-yl]acetamide Chemical compound C1=C(C(=O)CCl)C(NC(=O)C)=CC2=C1OCO2 CSZGVPCUMJDPAB-UHFFFAOYSA-N 0.000 description 2
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/18—Ethylenedioxybenzenes, not substituted on the hetero ring
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/62—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to atoms of the carbocyclic ring
- C07D317/66—Nitrogen atoms not forming part of a nitro radical
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78427591A | 1991-10-29 | 1991-10-29 | |
| US82672992A | 1992-01-28 | 1992-01-28 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO924158D0 NO924158D0 (no) | 1992-10-28 |
| NO924158L NO924158L (no) | 1993-04-30 |
| NO302073B1 true NO302073B1 (no) | 1998-01-19 |
Family
ID=27120258
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO924158A NO302073B1 (no) | 1991-10-29 | 1992-10-28 | Vannopplöselige camptothecin-derivater |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP0540099B1 (ru) |
| JP (2) | JP3020760B2 (ru) |
| KR (1) | KR100246154B1 (ru) |
| CN (1) | CN1072683A (ru) |
| AP (1) | AP306A (ru) |
| AT (1) | ATE136898T1 (ru) |
| AU (1) | AU657007B2 (ru) |
| CA (1) | CA2081580A1 (ru) |
| CZ (1) | CZ284023B6 (ru) |
| DE (1) | DE69209969T2 (ru) |
| DK (1) | DK0540099T3 (ru) |
| ES (1) | ES2086643T3 (ru) |
| FI (3) | FI104373B (ru) |
| GR (1) | GR3020120T3 (ru) |
| HU (2) | HU217970B (ru) |
| IL (1) | IL103571A (ru) |
| IS (1) | IS1708B (ru) |
| MX (1) | MX9206211A (ru) |
| MY (1) | MY108261A (ru) |
| NO (1) | NO302073B1 (ru) |
| NZ (1) | NZ244914A (ru) |
| OA (1) | OA09767A (ru) |
| RU (1) | RU2119921C1 (ru) |
| SK (1) | SK323792A3 (ru) |
| TW (1) | TW221994B (ru) |
Families Citing this family (40)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5364858A (en) * | 1987-03-31 | 1994-11-15 | Research Triangle Institute | Camptothecin analogs as potent inhibitors of topoisomerase I |
| US5552154A (en) | 1989-11-06 | 1996-09-03 | The Stehlin Foundation For Cancer Research | Method for treating cancer with water-insoluble s-camptothecin of the closed lactone ring form and derivatives thereof |
| US6080751A (en) * | 1992-01-14 | 2000-06-27 | The Stehlin Foundation For Cancer Research | Method for treating pancreatic cancer in humans with water-insoluble S-camptothecin of the closed lactone ring form and derivatives thereof |
| AP9300587A0 (en) * | 1992-11-12 | 1995-05-05 | Glaxo Inc | Water soluble camptothecin derivatives. |
| ES2186812T3 (es) * | 1993-01-15 | 2003-05-16 | Stehlin Foundation For Cancer | Tratamiento oral o intramuscular del cancer pancreatico con s-camptotecina insoluble en agua de la forma de anillo de lactona cerrado. |
| US5369127A (en) * | 1993-04-21 | 1994-11-29 | Allergan, Inc. | 1,3-benzodioxole and 1,2-dialkoxybenzene derivatives as ocular hypotensive agents |
| IS4152A (is) * | 1993-04-29 | 1994-10-30 | Glaxo Inc. | Vatnsuppleysanlegar Camptothecin afleiður og aðferð til framleiðslu þeirra |
| JPH08509742A (ja) * | 1993-05-03 | 1996-10-15 | スミスクライン・ビーチャム・コーポレイション | 置換メチレンジオキシ［３’，４’：６，７］インドリジノ［１，２−ｂ］キノリノン |
| 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 |
| US5491237A (en) * | 1994-05-03 | 1996-02-13 | Glaxo Wellcome Inc. | Intermediates in pharmaceutical camptothecin preparation |
| IT1269862B (it) * | 1994-05-30 | 1997-04-15 | Indena Spa | Alcaloidi da mappia foetida, loro uso e formulazioni che li contengono |
| US5646159A (en) * | 1994-07-20 | 1997-07-08 | Research Triangle Institute | Water-soluble esters of camptothecin compounds |
| KR960029336A (ko) | 1995-01-09 | 1996-08-17 | 김충환 | 캄토테신 유도체, 그의 제조 방법 및 이를 함유하는 항암제 |
| US5496952A (en) * | 1995-02-07 | 1996-03-05 | North Carolina State University | Method of making asymmetric DE ring intermediates for the synthesis of camptothecin and camptothecin analogs |
| US5670500A (en) * | 1995-05-31 | 1997-09-23 | Smithkline Beecham Corporation | Water soluble camptothecin analogs |
| ATE275132T1 (de) * | 1995-06-27 | 2004-09-15 | Takeda Chemical Industries Ltd | 4-acylamino(halogen)alkyl-chinolin derivate, deren herstellung und deren verwendung als melatonin-agonisten |
| SG50747A1 (en) * | 1995-08-02 | 1998-07-20 | Tanabe Seiyaku Co | Comptothecin derivatives |
| WO1997019085A1 (en) * | 1995-11-22 | 1997-05-29 | Research Triangle Institute | Camptothecin compounds with combined topoisomerase i inhibition and dna alkylation properties |
| CA2192725C (en) | 1995-12-28 | 2004-04-20 | Kenji Tsujihara | Camptothecin derivatives |
| SG116433A1 (en) * | 1996-10-30 | 2005-11-28 | Tanabe Seiyaku Co | S type 2-substituted hydroxy-2-indolidinylbutyric ester compounds and process for preparation thereof. |
| US6559309B2 (en) | 1996-11-01 | 2003-05-06 | Osi Pharmaceuticals, Inc. | Preparation of a camptothecin derivative by intramolecular cyclisation |
| US6207673B1 (en) | 1997-03-12 | 2001-03-27 | The University Of North Carolina At Chapel Hill | Covalent conjugates of topoisomerase I and topoisomerase II inhibitors |
| US6046209A (en) * | 1997-05-27 | 2000-04-04 | Smithkline Beecham Corporation | Water soluble camptothecin analogs |
| US6288072B1 (en) * | 1999-12-29 | 2001-09-11 | Monroe E. Wall | Camptothecin β-alanine esters with topoisomerase I inhibition |
| EP1278518B1 (en) | 2000-02-28 | 2006-11-08 | Pfizer Enterprises SARL | Synergistic combination for the treatment of colorectal cancer |
| US6548488B2 (en) | 2000-03-17 | 2003-04-15 | Aventis Pharma S.A. | Composition comprising camptothecin or a camptothecin derivative and an alkylating agent for the treatment of cancer |
| US6545010B2 (en) | 2000-03-17 | 2003-04-08 | Aventis Pharma S.A. | Composition comprising camptothecin or a camptothecin derivative and a platin derivative for the treatment of cancer |
| US6486320B2 (en) | 2000-09-15 | 2002-11-26 | Aventis Pharma S.A. | Preparation of camptothecin and of its derivatives |
| YU29803A (sh) | 2000-10-27 | 2006-05-25 | Aventis Pharma S.A. | Kombinacija kamptotekina i derivata stilbena za lečenje raka |
| ITRM20040240A1 (it) * | 2004-05-13 | 2004-08-13 | Ist Naz Stud Cura Dei Tumori | Camptotecine coniugate in posizione 7 con antagonisti delle integrine. |
| WO2006069344A2 (en) | 2004-12-22 | 2006-06-29 | Rutgers, The State University Of New Jersey | Controlled release hydrogels |
| WO2012050591A1 (en) | 2010-10-15 | 2012-04-19 | Rutgers, The State University Of New Jersey | Hydrogel formulation for dermal and ocular delivery |
| EP1998809B1 (en) | 2006-03-30 | 2014-06-25 | Drais Pharmaceuticals, Inc. | Camptothecin-cell penetrating peptide conjugates and pharmaceutical compositions containing the same |
| CN101407524B (zh) * | 2007-10-09 | 2012-07-18 | 江苏先声药物研究有限公司 | 噁嗪骈喜树碱衍生物及其制备方法和用途 |
| CN100592871C (zh) * | 2008-03-14 | 2010-03-03 | 浙江林学院 | 一种杀虫剂组合物及其加工方法 |
| ES2373172B1 (es) * | 2010-07-16 | 2012-12-10 | Consejo Superior De Investigaciones Científicas (Csic) | Proceso de obtención de derivados solubles en agua de 20 (s) camptotecina como agentes antitumorales. |
| US8980909B2 (en) | 2011-01-12 | 2015-03-17 | Crystal Biopharmaceutical Llc | HDAC inhibiting derivatives of camptothecin |
| IL277748B1 (en) * | 2018-04-06 | 2024-03-01 | Seagen Inc | Camptothecin peptide conjugates |
| CN110590796B (zh) * | 2018-06-12 | 2022-07-15 | 青岛海洋生物医药研究院股份有限公司 | 喜树碱衍生物及其制备方法和应用 |
| CN117769555A (zh) * | 2021-08-19 | 2024-03-26 | 先声再明医药有限公司 | 喜树碱衍生物、其药物组合物及其应用 |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5004758A (en) * | 1987-12-01 | 1991-04-02 | Smithkline Beecham Corporation | Water soluble camptothecin analogs useful for inhibiting the growth of animal tumor cells |
-
1992
- 1992-10-23 DE DE69209969T patent/DE69209969T2/de not_active Expired - Fee Related
- 1992-10-23 DK DK92203263.6T patent/DK0540099T3/da active
- 1992-10-23 AT AT92203263T patent/ATE136898T1/de not_active IP Right Cessation
- 1992-10-23 EP EP92203263A patent/EP0540099B1/en not_active Expired - Lifetime
- 1992-10-23 ES ES92203263T patent/ES2086643T3/es not_active Expired - Lifetime
- 1992-10-27 TW TW081108539A patent/TW221994B/zh active
- 1992-10-27 SK SK3237-92A patent/SK323792A3/sk unknown
- 1992-10-27 CZ CS923237A patent/CZ284023B6/cs not_active IP Right Cessation
- 1992-10-28 MX MX9206211A patent/MX9206211A/es unknown
- 1992-10-28 MY MYPI92001954A patent/MY108261A/en unknown
- 1992-10-28 NZ NZ244914A patent/NZ244914A/xx not_active IP Right Cessation
- 1992-10-28 IS IS3936A patent/IS1708B/is unknown
- 1992-10-28 KR KR1019920019884A patent/KR100246154B1/ko not_active IP Right Cessation
- 1992-10-28 CN CN92113782A patent/CN1072683A/zh not_active Withdrawn
- 1992-10-28 RU RU92004336A patent/RU2119921C1/ru not_active IP Right Cessation
- 1992-10-28 CA CA002081580A patent/CA2081580A1/en not_active Abandoned
- 1992-10-28 FI FI924878A patent/FI104373B/fi active
- 1992-10-28 JP JP4312862A patent/JP3020760B2/ja not_active Expired - Fee Related
- 1992-10-28 NO NO924158A patent/NO302073B1/no unknown
- 1992-10-28 AU AU27385/92A patent/AU657007B2/en not_active Ceased
- 1992-10-28 IL IL103571A patent/IL103571A/en not_active IP Right Cessation
- 1992-10-28 HU HU9203384A patent/HU217970B/hu not_active IP Right Cessation
- 1992-10-28 OA OA60295A patent/OA09767A/en unknown
- 1992-10-28 AP APAP/P/1992/000439A patent/AP306A/en active
-
1995
- 1995-06-14 HU HU95P/P00203P patent/HU211349A9/hu unknown
-
1996
- 1996-05-31 GR GR960401497T patent/GR3020120T3/el unknown
-
1998
- 1998-10-08 FI FI982185A patent/FI982185A/fi unknown
-
1999
- 1999-11-02 JP JP31294099A patent/JP3229298B2/ja not_active Expired - Fee Related
-
2002
- 2002-06-07 FI FI20021090A patent/FI20021090A/fi not_active Application Discontinuation
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