NO324308B1 - Fremgangsmate for fremstilling av Camptothecin-derivater, samt produkter av og mellomprodukter for slike forbindelser - Google Patents

Fremgangsmate for fremstilling av Camptothecin-derivater, samt produkter av og mellomprodukter for slike forbindelser Download PDF

Info

Publication number: NO324308B1
Authority: NO; Norway
Prior art keywords: alkyl; cycloalkyl; carbon atoms; hydrogen; hydroxy
Prior art date: 1995-11-02

Application number

NO19981970A

Other languages

English (en)

Norwegian (no)

Other versions

NO981970D0 (no

NO981970L (no

Inventor

Francis Gerard Fang

Shiping Xie

Original Assignee

Osi Pharm Inc

Priority date (The priority date 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 date listed.)

1995-11-02

Filing date

1998-04-30

Publication date

2007-09-24

1998-04-30 Application filed by Osi Pharm Inc filed Critical Osi Pharm Inc

1998-04-30 Publication of NO981970D0 publication Critical patent/NO981970D0/no

1998-06-30 Publication of NO981970L publication Critical patent/NO981970L/no

2007-09-24 Publication of NO324308B1 publication Critical patent/NO324308B1/no

Links

150000001875 compounds Chemical class 0.000 title claims abstract description 47
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 abstract description 18
239000000543 intermediate Substances 0.000 title abstract description 8
238000002360 preparation method Methods 0.000 title abstract description 5
238000000034 method Methods 0.000 title description 13
238000004519 manufacturing process Methods 0.000 claims abstract description 11
125000000217 alkyl group Chemical group 0.000 claims description 113
125000003545 alkoxy group Chemical group 0.000 claims description 70
239000001257 hydrogen Substances 0.000 claims description 45
229910052739 hydrogen Inorganic materials 0.000 claims description 45
-1 N-methylpyrrolyl Chemical group 0.000 claims description 34
125000004432 carbon atom Chemical group C* 0.000 claims description 32
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 31
125000000753 cycloalkyl group Chemical group 0.000 claims description 30
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 21
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
125000003118 aryl group Chemical group 0.000 claims description 12
125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 10
229910052736 halogen Inorganic materials 0.000 claims description 10
150000002367 halogens Chemical class 0.000 claims description 10
125000001424 substituent group Chemical group 0.000 claims description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
150000003839 salts Chemical class 0.000 claims description 8
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 7
125000004183 alkoxy alkyl group Chemical group 0.000 claims description 6
238000005906 dihydroxylation reaction Methods 0.000 claims description 6
125000000623 heterocyclic group Chemical group 0.000 claims description 6
150000002431 hydrogen Chemical class 0.000 claims description 6
125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 6
229910052757 nitrogen Inorganic materials 0.000 claims description 4
229910052760 oxygen Inorganic materials 0.000 claims description 4
229920006395 saturated elastomer Polymers 0.000 claims description 4
125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 3
125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
125000002837 carbocyclic group Chemical group 0.000 claims description 3
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
125000002541 furyl group Chemical group 0.000 claims description 3
125000002883 imidazolyl group Chemical group 0.000 claims description 3
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 3
125000004076 pyridyl group Chemical group 0.000 claims description 3
229910052717 sulfur Inorganic materials 0.000 claims description 3
125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 claims description 3
125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 2
125000003282 alkyl amino group Chemical group 0.000 claims description 2
125000003342 alkenyl group Chemical group 0.000 claims 5
UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims 2
KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 abstract description 10
229940127093 camptothecin Drugs 0.000 abstract 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 abstract description 10
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
239000000203 mixture Substances 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 11
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 10
239000007787 solid Substances 0.000 description 10
238000005481 NMR spectroscopy Methods 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 6
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 5
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 5
238000012512 characterization method Methods 0.000 description 5
239000011630 iodine Substances 0.000 description 5
229910052740 iodine Inorganic materials 0.000 description 5
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
230000015572 biosynthetic process Effects 0.000 description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
239000003054 catalyst Substances 0.000 description 4
230000003197 catalytic effect Effects 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
229910052801 chlorine Inorganic materials 0.000 description 4
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 4
229910052763 palladium Inorganic materials 0.000 description 4
239000003880 polar aprotic solvent Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000003586 protic polar solvent Substances 0.000 description 4
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
238000003756 stirring Methods 0.000 description 4
239000000126 substance Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
239000002585 base Substances 0.000 description 3
239000003153 chemical reaction reagent Substances 0.000 description 3
238000006900 dealkylation reaction Methods 0.000 description 3
238000010828 elution Methods 0.000 description 3
BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
TZSBVRWCWYMNAT-UHFFFAOYSA-N 4-ethyl-7-[[7-iodo-9-[(4-methylpiperazin-1-yl)methyl]-2,3-dihydro-[1,4]dioxino[2,3-g]quinolin-8-yl]methyl]-1h-pyrano[3,4-c]pyridin-8-one Chemical compound CCC1=COCC(C2=O)=C1C=CN2CC1=C(I)N=C2C=C3OCCOC3=CC2=C1CN1CCN(C)CC1 TZSBVRWCWYMNAT-UHFFFAOYSA-N 0.000 description 2
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
108090000790 Enzymes Proteins 0.000 description 2
102000004190 Enzymes Human genes 0.000 description 2
MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
108090001060 Lipase Proteins 0.000 description 2
239000004367 Lipase Substances 0.000 description 2
102000004882 Lipase Human genes 0.000 description 2
XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
125000004414 alkyl thio group Chemical group 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 2
238000006482 condensation reaction Methods 0.000 description 2
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 2
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000004128 high performance liquid chromatography Methods 0.000 description 2
239000013067 intermediate product Substances 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000003446 ligand Substances 0.000 description 2
235000019421 lipase Nutrition 0.000 description 2
HNQIVZYLYMDVSB-UHFFFAOYSA-N methanesulfonimidic acid Chemical compound CS(N)(=O)=O HNQIVZYLYMDVSB-UHFFFAOYSA-N 0.000 description 2
229910052762 osmium Inorganic materials 0.000 description 2
SYQBFIAQOQZEGI-UHFFFAOYSA-N osmium atom Chemical compound [Os] SYQBFIAQOQZEGI-UHFFFAOYSA-N 0.000 description 2
239000007800 oxidant agent Substances 0.000 description 2
238000007254 oxidation reaction Methods 0.000 description 2
230000001590 oxidative effect Effects 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
235000009518 sodium iodide Nutrition 0.000 description 2
GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 2
239000007858 starting material Substances 0.000 description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
230000009466 transformation Effects 0.000 description 2
238000000844 transformation Methods 0.000 description 2
IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical class OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 description 1
YUCBLVFHJWOYDN-HVLQGHBFSA-N 1,4-bis[(s)-[(2r,4s,5r)-5-ethyl-1-azabicyclo[2.2.2]octan-2-yl]-(6-methoxyquinolin-4-yl)methoxy]phthalazine Chemical compound C1=C(OC)C=C2C([C@H](OC=3C4=CC=CC=C4C(O[C@H]([C@@H]4N5CC[C@H]([C@H](C5)CC)C4)C=4C5=CC(OC)=CC=C5N=CC=4)=NN=3)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 YUCBLVFHJWOYDN-HVLQGHBFSA-N 0.000 description 1
BXYZFBZFOPCYGD-UHFFFAOYSA-N 3-[[3-[3-benzoyl-8-(trifluoromethyl)quinolin-4-yl]phenoxy]methyl]benzoic acid Chemical compound OC(=O)C1=CC=CC(COC=2C=C(C=CC=2)C=2C3=CC=CC(=C3N=CC=2C(=O)C=2C=CC=CC=2)C(F)(F)F)=C1 BXYZFBZFOPCYGD-UHFFFAOYSA-N 0.000 description 1
KXSPNNXIXSQDKH-UHFFFAOYSA-N 4-ethyl-8-methoxy-1h-pyrano[3,4-c]pyridine Chemical compound N1=CC=C2C(CC)=COCC2=C1OC KXSPNNXIXSQDKH-UHFFFAOYSA-N 0.000 description 1
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 1
241000228245 Aspergillus niger Species 0.000 description 1
241000759905 Camptotheca acuminata Species 0.000 description 1
108010015598 Chromobacterium viscosum lipase Proteins 0.000 description 1
235000021513 Cinchona Nutrition 0.000 description 1
241000157855 Cinchona Species 0.000 description 1
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
241000047214 Cyclocybe cylindracea Species 0.000 description 1
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
239000005977 Ethylene Substances 0.000 description 1
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
238000007341 Heck reaction Methods 0.000 description 1
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
LJOQGZACKSYWCH-AFHBHXEDSA-N Hydroquinidine Natural products C1=C(OC)C=C2C([C@@H](O)[C@H]3C[C@@H]4CCN3C[C@@H]4CC)=CC=NC2=C1 LJOQGZACKSYWCH-AFHBHXEDSA-N 0.000 description 1
238000006617 Intramolecular Heck reaction Methods 0.000 description 1
JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
238000006751 Mitsunobu reaction Methods 0.000 description 1
LFTLOKWAGJYHHR-UHFFFAOYSA-N N-methylmorpholine N-oxide Chemical compound CN1(=O)CCOCC1 LFTLOKWAGJYHHR-UHFFFAOYSA-N 0.000 description 1
229910002651 NO3 Inorganic materials 0.000 description 1
206010028980 Neoplasm Diseases 0.000 description 1
NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
229910019142 PO4 Inorganic materials 0.000 description 1
102000019280 Pancreatic lipases Human genes 0.000 description 1
108050006759 Pancreatic lipases Proteins 0.000 description 1
YNPNZTXNASCQKK-UHFFFAOYSA-N Phenanthrene Natural products C1=CC=C2C3=CC=CC=C3C=CC2=C1 YNPNZTXNASCQKK-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
101001003495 Pseudomonas fluorescens Lipase Proteins 0.000 description 1
101001064559 Pseudomonas fluorescens Lipase Proteins 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000003213 activating effect Effects 0.000 description 1
239000011149 active material Substances 0.000 description 1
229910001516 alkali metal iodide Inorganic materials 0.000 description 1
229930013930 alkaloid Natural products 0.000 description 1
230000000719 anti-leukaemic effect Effects 0.000 description 1
230000000259 anti-tumor effect Effects 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
238000006256 asymmetric dihydroxylation reaction Methods 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
125000005604 azodicarboxylate group Chemical group 0.000 description 1
229940045348 brown mixture Drugs 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
230000007541 cellular toxicity Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000000295 complement effect Effects 0.000 description 1
238000011109 contamination Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000012043 crude product Substances 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
230000006378 damage Effects 0.000 description 1
230000020335 dealkylation Effects 0.000 description 1
235000005911 diet Nutrition 0.000 description 1
230000037213 diet Effects 0.000 description 1
239000001177 diphosphate Substances 0.000 description 1
XPPKVPWEQAFLFU-UHFFFAOYSA-J diphosphate(4-) Chemical compound [O-]P([O-])(=O)OP([O-])([O-])=O XPPKVPWEQAFLFU-UHFFFAOYSA-J 0.000 description 1
235000011180 diphosphates Nutrition 0.000 description 1
DGODWNOPHMXOTR-UHFFFAOYSA-N dipotassium;dioxido(dioxo)osmium;dihydrate Chemical compound O.O.[K+].[K+].[O-][Os]([O-])(=O)=O DGODWNOPHMXOTR-UHFFFAOYSA-N 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
230000005611 electricity Effects 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
229960000811 hydroquinidine Drugs 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
IJKXJZJLJSCTHE-UHFFFAOYSA-N indolizin-1-ol Chemical compound C1=CC=CC2=C(O)C=CN21 IJKXJZJLJSCTHE-UHFFFAOYSA-N 0.000 description 1
230000006698 induction Effects 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
PANJMBIFGCKWBY-UHFFFAOYSA-N iron tricyanide Chemical compound N#C[Fe](C#N)C#N PANJMBIFGCKWBY-UHFFFAOYSA-N 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
229940049920 malate Drugs 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
239000000463 material Substances 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
ITATYELQCJRCCK-QMMMGPOBSA-N methyl (2s)-2-hydroxy-2-phenylacetate Chemical compound COC(=O)[C@@H](O)C1=CC=CC=C1 ITATYELQCJRCCK-QMMMGPOBSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
150000007524 organic acids Chemical class 0.000 description 1
235000005985 organic acids Nutrition 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
229910000489 osmium tetroxide Inorganic materials 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
239000001301 oxygen Substances 0.000 description 1
LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
239000003444 phase transfer catalyst Substances 0.000 description 1
239000010452 phosphate Substances 0.000 description 1
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
239000011591 potassium Substances 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
150000003140 primary amides Chemical class 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
238000000746 purification Methods 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
229960001860 salicylate Drugs 0.000 description 1
239000011780 sodium chloride Substances 0.000 description 1
235000010265 sodium sulphite Nutrition 0.000 description 1
239000012453 solvate Substances 0.000 description 1
238000010186 staining Methods 0.000 description 1
238000003860 storage Methods 0.000 description 1
KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
150000003463 sulfur Chemical class 0.000 description 1
239000000725 suspension Substances 0.000 description 1
229940095064 tartrate Drugs 0.000 description 1
239000012970 tertiary amine catalyst Substances 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
DPKBAXPHAYBPRL-UHFFFAOYSA-M tetrabutylazanium;iodide Chemical compound [I-].CCCC[N+](CCCC)(CCCC)CCCC DPKBAXPHAYBPRL-UHFFFAOYSA-M 0.000 description 1
150000004684 trihydrates Chemical group 0.000 description 1
COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
LFNXCUNDYSYVJY-UHFFFAOYSA-N tris(3-methylphenyl)phosphane Chemical compound CC1=CC=CC(P(C=2C=C(C)C=CC=2)C=2C=C(C)C=CC=2)=C1 LFNXCUNDYSYVJY-UHFFFAOYSA-N 0.000 description 1
WXAZIUYTQHYBFW-UHFFFAOYSA-N tris(4-methylphenyl)phosphane Chemical compound C1=CC(C)=CC=C1P(C=1C=CC(C)=CC=1)C1=CC=C(C)C=C1 WXAZIUYTQHYBFW-UHFFFAOYSA-N 0.000 description 1
238000005406 washing Methods 0.000 description 1
235000020138 yakult Nutrition 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
- C07D491/02—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 two hetero rings
- C07D491/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Preparation Of Compounds By Using Micro-Organisms (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

NO19981970A 1995-11-02 1998-04-30 Fremgangsmate for fremstilling av Camptothecin-derivater, samt produkter av og mellomprodukter for slike forbindelser NO324308B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US613895P	1995-11-02	1995-11-02
PCT/US1996/017574 WO1997016454A1 (en)	1995-11-02	1996-11-01	Method for preparing camptothecin derivatives

Publications (3)

Publication Number	Publication Date
NO981970D0 NO981970D0 (no)	1998-04-30
NO981970L NO981970L (no)	1998-06-30
NO324308B1 true NO324308B1 (no)	2007-09-24

Family

ID=21719492

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19981970A NO324308B1 (no)	1995-11-02	1998-04-30	Fremgangsmate for fremstilling av Camptothecin-derivater, samt produkter av og mellomprodukter for slike forbindelser

Country Status (17)

Country	Link
US (2)	US6143891A (pl)
EP (1)	EP0876373B1 (pl)
JP (1)	JP3499246B2 (pl)
AT (1)	ATE301659T1 (pl)
AU (1)	AU717315B2 (pl)
CA (1)	CA2236420A1 (pl)
CZ (1)	CZ133898A3 (pl)
DE (1)	DE69635057T2 (pl)
EA (1)	EA001400B1 (pl)
ES (1)	ES2247606T3 (pl)
HU (1)	HUP9802407A3 (pl)
IL (1)	IL124287A (pl)
IS (1)	IS2274B (pl)
NO (1)	NO324308B1 (pl)
NZ (1)	NZ322318A (pl)
PL (1)	PL186540B1 (pl)
WO (1)	WO1997016454A1 (pl)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US5491237A (en) *	1994-05-03	1996-02-13	Glaxo Wellcome Inc.	Intermediates in pharmaceutical camptothecin preparation
US6716982B2 (en)	1995-11-02	2004-04-06	Osi Pharmaceuticals, Inc.	Method for preparing camptothecin derivatives
US6559309B2 (en)	1996-11-01	2003-05-06	Osi Pharmaceuticals, Inc.	Preparation of a camptothecin derivative by intramolecular cyclisation
US6288072B1 (en) *	1999-12-29	2001-09-11	Monroe E. Wall	Camptothecin β-alanine esters with topoisomerase I inhibition
AR035684A1 (es)	2001-02-21	2004-06-23	Yakult Honsha Kk	Procedimiento para preparar 2'-amino-5'-hidroxipropiofenona, uso de la misma para la preparacion de analogos de camptotecina, procedimiento para prepararlos, compuestos intermediarios, procedimiento para preparar una cetona triciclica utilizada en la sintesis de analogos de camptotecina
WO2003068778A1 (en) *	2002-02-18	2003-08-21	Dr. Reddy's Laboratories Limited	A process for the preparation of 10-hydroxy-9-n,n-dimethylaminomethyl-5-(2'-fluoroethoxy)-20(s)-camptothecin hydrochloride
US6593334B1 (en)	2002-05-02	2003-07-15	The University Of North Carolina At Chapel Hill	Camptothecin-taxoid conjugates as antimitotic and antitumor agents
US7067666B2 (en) *	2003-06-27	2006-06-27	Research Triangle Institute	7-substituted camptothecin and camptothecin analogs and methods for producing the same
US20070207149A1 (en)	2004-04-27	2007-09-06	Wellstat Biologics Corporation	Cancer treatment using viruses and camptothecins
CA2612949C (en)	2005-07-14	2015-04-28	Wellstat Biologics Corporation	Cancer treatment using viruses, fluoropyrimidines and camptothecins
CN103288842B (zh) *	2012-02-24	2016-01-13	中国人民解放军第二军医大学	氟取代e环喜树碱类似物及其作为药物的用途
US10517961B2 (en)	2015-09-25	2019-12-31	ZY Therapeutics, Inc.	Drug formulation based on particulates comprising polysaccharide-vitamin conjugate

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA2095219A1 (en) *	1990-10-31	1992-05-01	Hameed S. Allaudeen	Substituted indolizino[1,2-b]quinolinones
WO1993016698A1 (en) *	1992-02-21	1993-09-02	Smithkline Beecham Corporation	SUBSTITUTED FURO[3',4':6,7]INDOLIZINO[1,2-b]QUINOLINONES

1996
- 1996-11-01 WO PCT/US1996/017574 patent/WO1997016454A1/en not_active Ceased
- 1996-11-01 EP EP96938728A patent/EP0876373B1/en not_active Expired - Lifetime
- 1996-11-01 NZ NZ322318A patent/NZ322318A/xx unknown
- 1996-11-01 AT AT96938728T patent/ATE301659T1/de not_active IP Right Cessation
- 1996-11-01 ES ES96938728T patent/ES2247606T3/es not_active Expired - Lifetime
- 1996-11-01 US US09/068,185 patent/US6143891A/en not_active Expired - Fee Related
- 1996-11-01 EA EA199800354A patent/EA001400B1/ru not_active IP Right Cessation
- 1996-11-01 IL IL12428796A patent/IL124287A/en not_active IP Right Cessation
- 1996-11-01 JP JP51758897A patent/JP3499246B2/ja not_active Expired - Fee Related
- 1996-11-01 HU HU9802407A patent/HUP9802407A3/hu unknown
- 1996-11-01 AU AU76038/96A patent/AU717315B2/en not_active Ceased
- 1996-11-01 CZ CZ981338A patent/CZ133898A3/cs unknown
- 1996-11-01 DE DE69635057T patent/DE69635057T2/de not_active Expired - Fee Related
- 1996-11-01 CA CA002236420A patent/CA2236420A1/en not_active Abandoned
- 1996-11-01 PL PL96326869A patent/PL186540B1/pl not_active IP Right Cessation
1998
- 1998-04-29 IS IS4730A patent/IS2274B/is unknown
- 1998-04-30 NO NO19981970A patent/NO324308B1/no unknown
2000
- 2000-08-15 US US09/638,945 patent/US6284891B1/en not_active Expired - Fee Related

Also Published As

Publication number	Publication date
EA001400B1 (ru)	2001-02-26
WO1997016454A1 (en)	1997-05-09
ES2247606T3 (es)	2006-03-01
IS2274B (is)	2007-09-15
HUP9802407A1 (hu)	1999-04-28
HUP9802407A3 (en)	2000-01-28
CZ133898A3 (cs)	1998-08-12
NO981970D0 (no)	1998-04-30
NO981970L (no)	1998-06-30
US6143891A (en)	2000-11-07
PL326869A1 (en)	1998-10-26
PL186540B1 (pl)	2004-01-30
JPH11515028A (ja)	1999-12-21
DE69635057D1 (de)	2005-09-15
EA199800354A1 (ru)	1999-02-25
EP0876373A1 (en)	1998-11-11
IS4730A (is)	1998-04-29
NZ322318A (en)	2000-01-28
CA2236420A1 (en)	1997-05-09
US6284891B1 (en)	2001-09-04
EP0876373B1 (en)	2005-08-10
DE69635057T2 (de)	2006-06-01
AU7603896A (en)	1997-05-22
ATE301659T1 (de)	2005-08-15
IL124287A (en)	2004-06-01
AU717315B2 (en)	2000-03-23
JP3499246B2 (ja)	2004-02-23

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