WO1995004736A1 - Process for the preparation of 9-amino camptothecin - Google Patents
Process for the preparation of 9-amino camptothecin Download PDFInfo
- Publication number
- WO1995004736A1 WO1995004736A1 PCT/EP1994/002370 EP9402370W WO9504736A1 WO 1995004736 A1 WO1995004736 A1 WO 1995004736A1 EP 9402370 W EP9402370 W EP 9402370W WO 9504736 A1 WO9504736 A1 WO 9504736A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- formula
- compound
- camptothecin
- amino
- nitro
- Prior art date
Links
- FUXVKZWTXQUGMW-FQEVSTJZSA-N 9-Aminocamptothecin Chemical compound C1=CC(N)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 FUXVKZWTXQUGMW-FQEVSTJZSA-N 0.000 title claims abstract description 31
- 238000000034 method Methods 0.000 title claims description 35
- 238000002360 preparation method Methods 0.000 title claims description 7
- 150000001875 compounds Chemical class 0.000 claims abstract description 98
- XQHHKVBMHNTWSH-FQEVSTJZSA-N chembl306181 Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1[N+]([O-])=O XQHHKVBMHNTWSH-FQEVSTJZSA-N 0.000 claims abstract description 11
- 230000000802 nitrating effect Effects 0.000 claims abstract description 8
- 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 claims description 23
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 19
- 238000006243 chemical reaction Methods 0.000 claims description 19
- 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 19
- 239000000203 mixture Substances 0.000 claims description 19
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims description 17
- 229940127093 camptothecin Drugs 0.000 claims description 17
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 14
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 13
- 239000003638 chemical reducing agent Substances 0.000 claims description 12
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 claims description 12
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 12
- 229910017604 nitric acid Inorganic materials 0.000 claims description 11
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 238000006396 nitration reaction Methods 0.000 claims description 7
- 229910052763 palladium Inorganic materials 0.000 claims description 7
- 229910052697 platinum Inorganic materials 0.000 claims description 7
- VHXNKPBCCMUMSW-FQEVSTJZSA-N rubitecan Chemical compound C1=CC([N+]([O-])=O)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VHXNKPBCCMUMSW-FQEVSTJZSA-N 0.000 claims description 7
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 235000019253 formic acid Nutrition 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- FGIUAXJPYTZDNR-UHFFFAOYSA-N potassium nitrate Chemical compound [K+].[O-][N+]([O-])=O FGIUAXJPYTZDNR-UHFFFAOYSA-N 0.000 claims description 6
- 229910052703 rhodium Inorganic materials 0.000 claims description 6
- 239000010948 rhodium Substances 0.000 claims description 6
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 6
- 235000011149 sulphuric acid Nutrition 0.000 claims description 6
- PTMFUWGXPRYYMC-UHFFFAOYSA-N triethylazanium;formate Chemical compound OC=O.CCN(CC)CC PTMFUWGXPRYYMC-UHFFFAOYSA-N 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 5
- DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 claims description 5
- 229910021589 Copper(I) bromide Inorganic materials 0.000 claims description 4
- 229910021591 Copper(I) chloride Inorganic materials 0.000 claims description 4
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 claims description 4
- 229910052707 ruthenium Inorganic materials 0.000 claims description 4
- 239000003085 diluting agent Substances 0.000 claims description 3
- 239000004323 potassium nitrate Substances 0.000 claims description 3
- 235000010333 potassium nitrate Nutrition 0.000 claims description 3
- 238000000926 separation method Methods 0.000 claims description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 229910052742 iron Inorganic materials 0.000 claims description 2
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 238000004064 recycling Methods 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims 1
- 239000003937 drug carrier Substances 0.000 claims 1
- -1 9-nitro-20(S)-camptothecin compound Chemical class 0.000 abstract description 28
- QPUDSTGASYNWEO-FQEVSTJZSA-N 12-amino-20(s)-camptohecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1N QPUDSTGASYNWEO-FQEVSTJZSA-N 0.000 abstract description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 45
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000006722 reduction reaction Methods 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- 239000000047 product Substances 0.000 description 15
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
- 239000011541 reaction mixture Substances 0.000 description 13
- 239000002904 solvent Substances 0.000 description 13
- 239000007787 solid Substances 0.000 description 11
- 239000000243 solution Substances 0.000 description 11
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 10
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 9
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- TZCXTZWJZNENPQ-UHFFFAOYSA-L barium sulfate Chemical compound [Ba+2].[O-]S([O-])(=O)=O TZCXTZWJZNENPQ-UHFFFAOYSA-L 0.000 description 8
- 230000002829 reductive effect Effects 0.000 description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 8
- 206010028980 Neoplasm Diseases 0.000 description 7
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 238000013459 approach Methods 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 229910000019 calcium carbonate Inorganic materials 0.000 description 5
- 235000010216 calcium carbonate Nutrition 0.000 description 5
- 201000011510 cancer Diseases 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 5
- MUMZUERVLWJKNR-UHFFFAOYSA-N oxoplatinum Chemical compound [Pt]=O MUMZUERVLWJKNR-UHFFFAOYSA-N 0.000 description 5
- 229910003446 platinum oxide Inorganic materials 0.000 description 5
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 4
- 229910052799 carbon Inorganic materials 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- 150000007530 organic bases Chemical class 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 235000010288 sodium nitrite Nutrition 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- XWKFPIODWVPXLX-UHFFFAOYSA-N 2-methyl-5-methylpyridine Natural products CC1=CC=C(C)N=C1 XWKFPIODWVPXLX-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 150000007513 acids Chemical class 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 238000001035 drying Methods 0.000 description 3
- 229910052751 metal Inorganic materials 0.000 description 3
- 239000002184 metal Substances 0.000 description 3
- 230000000269 nucleophilic effect Effects 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 3
- OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000037396 body weight Effects 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 238000000354 decomposition reaction Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000012433 hydrogen halide Substances 0.000 description 2
- 229910000039 hydrogen halide Inorganic materials 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 239000003999 initiator Substances 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 238000011031 large-scale manufacturing process Methods 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 150000002739 metals Chemical class 0.000 description 2
- 150000002826 nitrites Chemical class 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000001117 sulphuric acid Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- MVJKXJPDBTXECY-UHFFFAOYSA-N trifluoroborane;hydrate Chemical compound O.FB(F)F MVJKXJPDBTXECY-UHFFFAOYSA-N 0.000 description 2
- 239000002699 waste material Substances 0.000 description 2
- 102000003915 DNA Topoisomerases Human genes 0.000 description 1
- 108090000323 DNA Topoisomerases Proteins 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound 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 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229910019020 PtO2 Inorganic materials 0.000 description 1
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 1
- 229960003116 amyl nitrite Drugs 0.000 description 1
- 229940111121 antirheumatic drug quinolines Drugs 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 244000309464 bull Species 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 210000001072 colon Anatomy 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000664 diazo group Chemical group [N-]=[N+]=[*] 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 150000003057 platinum Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003248 quinolines Chemical class 0.000 description 1
- 238000011937 reductive transformation Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- IOGXOCVLYRDXLW-UHFFFAOYSA-N tert-butyl nitrite Chemical compound CC(C)(C)ON=O IOGXOCVLYRDXLW-UHFFFAOYSA-N 0.000 description 1
- 239000012414 tert-butyl nitrite Substances 0.000 description 1
- 238000006257 total synthesis reaction 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
- C07D491/22—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)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Priority Applications (7)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA002145514A CA2145514C (en) | 1993-08-06 | 1994-07-18 | Process for the preparation of 9-amino camptothecin |
| KR1019950701312A KR950703565A (ko) | 1993-08-06 | 1994-07-18 | 9-아미노 캄프토테신의 제조방법(Process for the preparation of 9-amino camptothecin) |
| JP50617895A JP3556223B2 (ja) | 1993-08-06 | 1994-07-18 | ９−アミノカンプトテシンの製造方法 |
| RU95112573A RU2145325C1 (ru) | 1993-08-06 | 1994-07-18 | Способы получения 9-аминокамптотецина, промежуточные продукты и способ их получения |
| AU72290/94A AU678587B2 (en) | 1993-08-06 | 1994-07-18 | Process for the preparation of 9-amino camptothecin |
| EP94921656A EP0663914A1 (en) | 1993-08-06 | 1994-07-18 | Process for the preparation of 9-amino camptothecin |
| FI951581A FI951581A7 (fi) | 1993-08-06 | 1995-04-03 | Menetelmä 9-aminokamptotesiinin valmistamiseksi |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB939316352A GB9316352D0 (en) | 1993-08-06 | 1993-08-06 | Process for the preparation of 9-amino camptothecin |
| GB9316352.5 | 1993-08-06 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995004736A1 true WO1995004736A1 (en) | 1995-02-16 |
Family
ID=10740090
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1994/002370 WO1995004736A1 (en) | 1993-08-06 | 1994-07-18 | Process for the preparation of 9-amino camptothecin |
Country Status (15)
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995032207A1 (en) * | 1994-05-24 | 1995-11-30 | Pharmacia S.P.A. | Method for the preparation of 9-amino camptothecin |
| RU2164917C2 (ru) * | 1995-04-07 | 2001-04-10 | Фармация Энд Апджон Компани | Новые промежуточные продукты и способ получения производных камптотецина (срт-11) и родственных соединений |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9319944D0 (en) * | 1993-09-28 | 1993-11-17 | Erba Carlo Spa | Process for the preparation of 9-amino camptothecin |
| CN1324032C (zh) * | 2004-01-07 | 2007-07-04 | 重庆医药工业研究院有限责任公司 | 一种新的9－硝基喜树碱晶型和药物组合物 |
| CN1312155C (zh) * | 2005-01-21 | 2007-04-25 | 华东理工大学 | 一种分离纯化9－硝基喜树碱的方法 |
| CN102731516B (zh) * | 2011-04-07 | 2014-07-02 | 宁波天衡药业股份有限公司 | 一类具有抗肿瘤活性的喜树碱衍生物 |
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| DE2150234A1 (de) * | 1971-10-08 | 1973-04-12 | Basf Ag | Verfahren zur herstellung von camptothecin und camptothecin-derivaten |
| US4894456A (en) * | 1987-03-31 | 1990-01-16 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| EP0538534A1 (en) * | 1987-04-14 | 1993-04-28 | Research Triangle Institute | Improved process for chemical reactions on camptothecin or analogs thereof |
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| US5122606A (en) * | 1987-04-14 | 1992-06-16 | Research Triangle Institute | 10,11-methylenedioxy camptothecins |
| US5225404A (en) * | 1989-11-06 | 1993-07-06 | New York University | Methods of treating colon tumors with tumor-inhibiting camptothecin compounds |
| DE4134885C2 (de) * | 1991-10-23 | 1994-04-07 | Praezisions Ventil Gmbh | Betätigungsaufsatz für einen Sprühbehälter |
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-
1994
- 1994-07-18 EP EP94921656A patent/EP0663914A1/en not_active Withdrawn
- 1994-07-18 CN CN94190581A patent/CN1048296C/zh not_active Expired - Fee Related
- 1994-07-18 WO PCT/EP1994/002370 patent/WO1995004736A1/en not_active Application Discontinuation
- 1994-07-18 AU AU72290/94A patent/AU678587B2/en not_active Ceased
- 1994-07-18 HU HU9501319A patent/HUT71240A/hu unknown
- 1994-07-18 KR KR1019950701312A patent/KR950703565A/ko not_active Ceased
- 1994-07-18 JP JP50617895A patent/JP3556223B2/ja not_active Expired - Fee Related
- 1994-07-18 CA CA002145514A patent/CA2145514C/en not_active Expired - Fee Related
- 1994-07-18 RU RU95112573A patent/RU2145325C1/ru active
- 1994-08-02 US US08/284,129 patent/US6403603B1/en not_active Expired - Fee Related
- 1994-08-03 IL IL110553A patent/IL110553A/xx not_active IP Right Cessation
- 1994-08-03 TW TW083107096A patent/TW269691B/zh active
- 1994-08-05 ZA ZA945878A patent/ZA945878B/xx unknown
-
1995
- 1995-04-03 FI FI951581A patent/FI951581A7/fi unknown
-
2004
- 2004-03-01 JP JP2004055749A patent/JP2004217665A/ja not_active Withdrawn
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| DE2150234A1 (de) * | 1971-10-08 | 1973-04-12 | Basf Ag | Verfahren zur herstellung von camptothecin und camptothecin-derivaten |
| US4894456A (en) * | 1987-03-31 | 1990-01-16 | Research Triangle Institute | Synthesis of camptothecin and analogs thereof |
| EP0538534A1 (en) * | 1987-04-14 | 1993-04-28 | Research Triangle Institute | Improved process for chemical reactions on camptothecin or analogs thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1995032207A1 (en) * | 1994-05-24 | 1995-11-30 | Pharmacia S.P.A. | Method for the preparation of 9-amino camptothecin |
| US5840899A (en) * | 1994-05-24 | 1998-11-24 | Pharmacia S.P.A. | Method for the preparation of 9-amino camptothecin |
| RU2164917C2 (ru) * | 1995-04-07 | 2001-04-10 | Фармация Энд Апджон Компани | Новые промежуточные продукты и способ получения производных камптотецина (срт-11) и родственных соединений |
Also Published As
| Publication number | Publication date |
|---|---|
| US6403603B1 (en) | 2002-06-11 |
| CA2145514C (en) | 2006-06-06 |
| ZA945878B (en) | 1995-03-10 |
| FI951581A0 (fi) | 1995-04-03 |
| RU95112573A (ru) | 1997-02-20 |
| IL110553A (en) | 1997-03-18 |
| AU7229094A (en) | 1995-02-28 |
| CN1048296C (zh) | 2000-01-12 |
| KR950703565A (ko) | 1995-09-20 |
| GB9316352D0 (en) | 1993-09-22 |
| TW269691B (GUID-C5D7CC26-194C-43D0-91A1-9AE8C70A9BFF.html) | 1996-02-01 |
| JP2004217665A (ja) | 2004-08-05 |
| JPH08506597A (ja) | 1996-07-16 |
| EP0663914A1 (en) | 1995-07-26 |
| HUT71240A (en) | 1995-11-28 |
| FI951581A7 (fi) | 1995-04-03 |
| RU2145325C1 (ru) | 2000-02-10 |
| CN1113384A (zh) | 1995-12-13 |
| IL110553A0 (en) | 1994-11-11 |
| CA2145514A1 (en) | 1995-02-16 |
| JP3556223B2 (ja) | 2004-08-18 |
| AU678587B2 (en) | 1997-06-05 |
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