FI106204B - Menetelmä mono- ja bis-alkyyliaminoantrasykliiniglykosidien valmistamiseksi - Google Patents

Menetelmä mono- ja bis-alkyyliaminoantrasykliiniglykosidien valmistamiseksi Download PDF

Info

Publication number: FI106204B
Authority: FI; Finland
Prior art keywords: formula; group; hydrogen; process according; hydroxy
Prior art date: 1991-07-05

Application number

FI940011A

Other languages

English (en)

Finnish (fi)

Swedish (sv)

Other versions

FI940011A0 (fi

FI940011A (fi

Inventor

Nicola Mongelli

Antonino Suarato

Michele Caruso

Alberto Bargiotti

Daniela Faiardi

Original Assignee

Pharmacia & Upjohn Spa

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.)

1991-07-05

Filing date

1994-01-03

Publication date

2000-12-15

1994-01-03 Application filed by Pharmacia & Upjohn Spa filed Critical Pharmacia & Upjohn Spa

1994-01-03 Publication of FI940011A0 publication Critical patent/FI940011A0/fi

1994-01-03 Publication of FI940011A publication Critical patent/FI940011A/fi

2000-12-15 Application granted granted Critical

2000-12-15 Publication of FI106204B publication Critical patent/FI106204B/fi

Links

238000000034 method Methods 0.000 title claims abstract description 38
229930182470 glycoside Natural products 0.000 title claims abstract description 34
150000002338 glycosides Chemical class 0.000 title claims abstract description 34
229940045799 anthracyclines and related substance Drugs 0.000 title claims abstract description 33
238000002360 preparation method Methods 0.000 title claims abstract description 13
150000001875 compounds Chemical class 0.000 claims abstract description 39
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 37
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 31
239000001257 hydrogen Substances 0.000 claims abstract description 29
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 14
229910052736 halogen Chemical group 0.000 claims abstract description 14
150000002367 halogens Chemical group 0.000 claims abstract description 14
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 13
150000003839 salts Chemical class 0.000 claims abstract description 13
-1 nitro, amino, methoxy Chemical group 0.000 claims abstract description 10
125000003118 aryl group Chemical group 0.000 claims abstract description 9
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 9
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 54
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 18
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 14
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 12
125000001309 chloro group Chemical group Cl* 0.000 claims description 12
239000002253 acid Substances 0.000 claims description 10
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical group CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 8
239000000741 silica gel Substances 0.000 claims description 8
229910002027 silica gel Inorganic materials 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 7
QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 claims description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 6
230000000259 anti-tumor effect Effects 0.000 claims description 6
239000000010 aprotic solvent Substances 0.000 claims description 6
238000004587 chromatography analysis Methods 0.000 claims description 6
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
125000006239 protecting group Chemical group 0.000 claims description 5
239000000203 mixture Substances 0.000 claims description 4
239000003880 polar aprotic solvent Substances 0.000 claims description 4
230000035484 reaction time Effects 0.000 claims description 4
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 claims description 4
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims description 3
229910052794 bromium Inorganic materials 0.000 claims description 3
229910052801 chlorine Inorganic materials 0.000 claims description 3
239000003480 eluent Substances 0.000 claims description 3
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
239000000460 chlorine Substances 0.000 claims description 2
229910052740 iodine Inorganic materials 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Substances [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 claims description 2
150000003512 tertiary amines Chemical class 0.000 claims 2
238000004519 manufacturing process Methods 0.000 claims 1
239000011159 matrix material Substances 0.000 claims 1
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 1
239000011877 solvent mixture Substances 0.000 claims 1
239000002246 antineoplastic agent Substances 0.000 abstract description 2
230000000694 effects Effects 0.000 abstract description 2
125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
239000008194 pharmaceutical composition Substances 0.000 abstract 1
AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 35
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 STQGQHZAVUOBTE-VGBVRHCVSA-N 0.000 description 24
229960000975 daunorubicin Drugs 0.000 description 22
STQGQHZAVUOBTE-UHFFFAOYSA-N 7-Cyan-hept-2t-en-4,6-diinsaeure Natural products C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)(C(C)=O)CC1OC1CC(N)C(O)C(C)O1 STQGQHZAVUOBTE-UHFFFAOYSA-N 0.000 description 21
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
229960004679 doxorubicin Drugs 0.000 description 14
229910052757 nitrogen Inorganic materials 0.000 description 14
XDXDZDZNSLXDNA-TZNDIEGXSA-N Idarubicin Chemical compound C1[C@H](N)[C@H](O)[C@H](C)O[C@H]1O[C@@H]1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2C[C@@](O)(C(C)=O)C1 XDXDZDZNSLXDNA-TZNDIEGXSA-N 0.000 description 10
125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 9
238000010828 elution Methods 0.000 description 9
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
XDXDZDZNSLXDNA-UHFFFAOYSA-N Idarubicin Natural products C1C(N)C(O)C(C)OC1OC1C2=C(O)C(C(=O)C3=CC=CC=C3C3=O)=C3C(O)=C2CC(O)(C(C)=O)C1 XDXDZDZNSLXDNA-UHFFFAOYSA-N 0.000 description 6
238000000434 field desorption mass spectrometry Methods 0.000 description 6
229960000908 idarubicin Drugs 0.000 description 6
QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 description 5
208000032839 leukemia Diseases 0.000 description 5
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 4
238000006243 chemical reaction Methods 0.000 description 4
238000003818 flash chromatography Methods 0.000 description 4
239000002904 solvent Substances 0.000 description 4
210000004027 cell Anatomy 0.000 description 3
239000010779 crude oil Substances 0.000 description 3
239000012299 nitrogen atmosphere Substances 0.000 description 3
239000000377 silicon dioxide Substances 0.000 description 3
RQFUZUMFPRMVDX-UHFFFAOYSA-N 3-Bromo-1-propanol Chemical compound OCCCBr RQFUZUMFPRMVDX-UHFFFAOYSA-N 0.000 description 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
241001465754 Metazoa Species 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
238000010306 acid treatment Methods 0.000 description 2
201000010897 colon adenocarcinoma Diseases 0.000 description 2
208000029742 colonic neoplasm Diseases 0.000 description 2
230000034994 death Effects 0.000 description 2
231100000517 death Toxicity 0.000 description 2
239000012458 free base Substances 0.000 description 2
238000000338 in vitro Methods 0.000 description 2
231100000572 poisoning Toxicity 0.000 description 2
230000000607 poisoning effect Effects 0.000 description 2
239000011541 reaction mixture Substances 0.000 description 2
238000003756 stirring Methods 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
238000002054 transplantation Methods 0.000 description 2
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 2
STQGQHZAVUOBTE-RPDDNNBZSA-N (7s,9s)-9-acetyl-7-[(2r,4s,5r,6s)-4-amino-5-hydroxy-6-methyloxan-2-yl]oxy-6,9,11-trihydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(C)=O)[C@H]1C[C@H](N)[C@@H](O)[C@H](C)O1 STQGQHZAVUOBTE-RPDDNNBZSA-N 0.000 description 1
WZZBNLYBHUDSHF-DHLKQENFSA-N 1-[(3s,4s)-4-[8-(2-chloro-4-pyrimidin-2-yloxyphenyl)-7-fluoro-2-methylimidazo[4,5-c]quinolin-1-yl]-3-fluoropiperidin-1-yl]-2-hydroxyethanone Chemical compound CC1=NC2=CN=C3C=C(F)C(C=4C(=CC(OC=5N=CC=CN=5)=CC=4)Cl)=CC3=C2N1[C@H]1CCN(C(=O)CO)C[C@@H]1F WZZBNLYBHUDSHF-DHLKQENFSA-N 0.000 description 1
125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
206010003445 Ascites Diseases 0.000 description 1
101000762938 Homo sapiens TOX high mobility group box family member 4 Proteins 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
241001529936 Murinae Species 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
102100026749 TOX high mobility group box family member 4 Human genes 0.000 description 1
125000000217 alkyl group Chemical group 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
150000001412 amines Chemical class 0.000 description 1
238000003556 assay Methods 0.000 description 1
230000000975 bioactive effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
230000005757 colony formation Effects 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000013058 crude material Substances 0.000 description 1
230000001472 cytotoxic effect Effects 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
LLTVGKHHDXGLMR-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.OC.ClCCl LLTVGKHHDXGLMR-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
210000005260 human cell Anatomy 0.000 description 1
238000001727 in vivo Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 1
235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
229920000136 polysorbate Polymers 0.000 description 1
229920000053 polysorbate 80 Polymers 0.000 description 1
238000000746 purification Methods 0.000 description 1
AOJFQRQNPXYVLM-UHFFFAOYSA-N pyridin-1-ium;chloride Chemical compound [Cl-].C1=CC=[NH+]C=C1 AOJFQRQNPXYVLM-UHFFFAOYSA-N 0.000 description 1
229920006395 saturated elastomer Polymers 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
239000007858 starting material Substances 0.000 description 1

Classifications

- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
- C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
- C07H15/20—Carbocyclic rings
- C07H15/24—Condensed ring systems having three or more rings
- C07H15/252—Naphthacene radicals, e.g. daunomycins, adriamycins

Landscapes

Health & Medical Sciences (AREA)
Chemical & Material Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Molecular Biology (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Animal Behavior & Ethology (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Biochemistry (AREA)
Engineering & Computer Science (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Epidemiology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

FI940011A 1991-07-05 1994-01-03 Menetelmä mono- ja bis-alkyyliaminoantrasykliiniglykosidien valmistamiseksi FI106204B (fi)

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB919114549A GB9114549D0 (en)	1991-07-05	1991-07-05	Mono and bis alkylamino-anthracyclines
GB9114549		1991-07-05
EP9201504		1992-07-03
PCT/EP1992/001504 WO1993001201A1 (fr)	1991-07-05	1992-07-03	Anthracyclines monoalkylamino et bisalkylamino

Publications (3)

Publication Number	Publication Date
FI940011A0 FI940011A0 (fi)	1994-01-03
FI940011A FI940011A (fi)	1994-01-03
FI106204B true FI106204B (fi)	2000-12-15

Family

ID=10697877

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
FI940011A FI106204B (fi)	1991-07-05	1994-01-03	Menetelmä mono- ja bis-alkyyliaminoantrasykliiniglykosidien valmistamiseksi

Country Status (24)

Country	Link
US (1)	US5496808A (fr)
EP (1)	EP0521458B1 (fr)
JP (1)	JP3153552B2 (fr)
KR (1)	KR100235365B1 (fr)
CN (1)	CN1031878C (fr)
AT (1)	ATE134376T1 (fr)
AU (1)	AU661012B2 (fr)
CA (1)	CA2112818C (fr)
CZ (1)	CZ2494A3 (fr)
DE (1)	DE69208400T2 (fr)
FI (1)	FI106204B (fr)
GB (1)	GB9114549D0 (fr)
GR (1)	GR3019429T3 (fr)
HK (1)	HK1006460A1 (fr)
HU (1)	HU218913B (fr)
IE (1)	IE76921B1 (fr)
IL (1)	IL102409A (fr)
MX (1)	MX9203928A (fr)
NO (1)	NO300099B1 (fr)
NZ (1)	NZ243450A (fr)
RU (1)	RU2118328C1 (fr)
TW (1)	TW201753B (fr)
WO (1)	WO1993001201A1 (fr)
ZA (1)	ZA924971B (fr)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB9325420D0 (en) *	1993-12-13	1994-02-16	Erba Carlo Spa	4'-o-sulfonyl-anthracycline derivatives
CA2199734A1 (fr) *	1994-09-12	1996-03-21	Fraser Aird	Facteur inhibiteur de liberation de la corticotropine et procedes d'utilisation
EP0768317B1 (fr) *	1995-10-16	1999-01-27	Kyowa Hakko Kogyo Co., Ltd.	Composés UCK14
DE19548474A1 (de) *	1995-12-22	1997-06-26	Wacker Chemie Gmbh	Aliphatisch ungesättigte Reste aufweisende Organopolysiloxane, deren Herstellung und deren Verwendung in vernetzbaren Massen
GB9613433D0 (en) *	1996-06-26	1996-08-28	Pharmacia Spa	Fluoro labelled anthracyclinone and anthracycline derivatives
US6086876A (en) *	1997-02-07	2000-07-11	The Wistar Insitute	Methods and compositions for the inhibition of interleukin-12 production
GB9806324D0 (en) *	1998-03-24	1998-05-20	Pharmacia & Upjohn Spa	Antitumour synergetic composition
GB9904386D0 (en) *	1999-02-25	1999-04-21	Pharmacia & Upjohn Spa	Antitumour synergistic composition
GB9904387D0 (en) *	1999-02-25	1999-04-21	Pharmacia & Upjohn Spa	Antitumour synergistic composition

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU570439B2 (en) *	1983-03-28	1988-03-17	Compression Labs, Inc.	A combined intraframe and interframe transform coding system
US4591637A (en) *	1985-01-17	1986-05-27	Sri International	Open chain-morpholino adriamycins
FR2591599B1 (fr) *	1985-12-17	1988-08-05	Hoechst Lab	Nouvelles anthracyclines et medicaments les contenant
DE3842836A1 (de) *	1988-12-20	1990-06-21	Behringwerke Ag	Rhodomycine mit einer modifizierten kohlenhydrat-einheit

1991
- 1991-07-05 GB GB919114549A patent/GB9114549D0/en active Pending
1992
- 1992-06-26 US US07/904,650 patent/US5496808A/en not_active Expired - Fee Related
- 1992-06-30 EP EP92111054A patent/EP0521458B1/fr not_active Expired - Lifetime
- 1992-06-30 AT AT92111054T patent/ATE134376T1/de active
- 1992-06-30 DE DE69208400T patent/DE69208400T2/de not_active Expired - Fee Related
- 1992-07-03 CA CA002112818A patent/CA2112818C/fr not_active Expired - Fee Related
- 1992-07-03 ZA ZA924971A patent/ZA924971B/xx unknown
- 1992-07-03 MX MX9203928A patent/MX9203928A/es not_active IP Right Cessation
- 1992-07-03 WO PCT/EP1992/001504 patent/WO1993001201A1/fr not_active Application Discontinuation
- 1992-07-03 IE IE922177A patent/IE76921B1/en not_active IP Right Cessation
- 1992-07-03 KR KR1019940700015A patent/KR100235365B1/ko not_active IP Right Cessation
- 1992-07-03 JP JP50195893A patent/JP3153552B2/ja not_active Expired - Fee Related
- 1992-07-03 CZ CZ9424A patent/CZ2494A3/cs unknown
- 1992-07-03 RU RU94021658A patent/RU2118328C1/ru active
- 1992-07-03 HU HU9400022A patent/HU218913B/hu not_active IP Right Cessation
- 1992-07-03 AU AU22294/92A patent/AU661012B2/en not_active Ceased
- 1992-07-03 IL IL10240992A patent/IL102409A/en not_active IP Right Cessation
- 1992-07-04 CN CN92108867A patent/CN1031878C/zh not_active Expired - Fee Related
- 1992-07-04 TW TW081105323A patent/TW201753B/zh active
- 1992-07-06 NZ NZ243450A patent/NZ243450A/en unknown
1994
- 1994-01-03 FI FI940011A patent/FI106204B/fi active
- 1994-01-04 NO NO940026A patent/NO300099B1/no not_active IP Right Cessation
1996
- 1996-03-27 GR GR960400814T patent/GR3019429T3/el unknown
1998
- 1998-06-19 HK HK98105711A patent/HK1006460A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
GR3019429T3 (en)	1996-06-30
IL102409A0 (en)	1993-01-14
CA2112818C (fr)	2003-02-04
TW201753B (fr)	1993-03-11
IE922177A1 (en)	1993-01-13
CA2112818A1 (fr)	1993-01-21
US5496808A (en)	1996-03-05
NO940026L (no)	1994-02-16
NZ243450A (en)	1993-11-25
HU218913B (hu)	2000-12-28
FI940011A0 (fi)	1994-01-03
WO1993001201A1 (fr)	1993-01-21
FI940011A (fi)	1994-01-03
CN1031878C (zh)	1996-05-29
EP0521458B1 (fr)	1996-02-21
RU2118328C1 (ru)	1998-08-27
KR100235365B1 (ko)	1999-12-15
ZA924971B (en)	1993-03-31
HU9400022D0 (en)	1994-05-30
DE69208400D1 (de)	1996-03-28
JP3153552B2 (ja)	2001-04-09
CZ2494A3 (en)	1994-07-13
DE69208400T2 (de)	1996-06-27
EP0521458A1 (fr)	1993-01-07
NO300099B1 (no)	1997-04-07
JPH06508841A (ja)	1994-10-06
IL102409A (en)	1995-12-08
ATE134376T1 (de)	1996-03-15
HUT70480A (en)	1995-10-30
HK1006460A1 (en)	1999-02-26
NO940026D0 (no)	1994-01-04
AU661012B2 (en)	1995-07-13
GB9114549D0 (en)	1991-08-21
AU2229492A (en)	1993-02-11
CN1069981A (zh)	1993-03-17
MX9203928A (es)	1993-04-01
IE76921B1 (en)	1997-11-05

Legal Events

Date	Code	Title	Description
1997-01-21	GB	Transfer or assigment of application	Owner name: PHARMACIA & UPJOHN S.P.A.

Publication	Publication Date	Title
EP1067933B1 (fr)	2007-08-15	Ecteine-ascidines semi-synthetiques
FI106204B (fi)	2000-12-15	Menetelmä mono- ja bis-alkyyliaminoantrasykliiniglykosidien valmistamiseksi
EP0614898B1 (fr)	2003-05-07	Derive indole, procede pour sa fabrication, et son usage medicinal
IL96643A (en)	1995-01-24	3 '- Dahmino -'S) - 2 ") - 3 (- Methoxy - 4" - Morpholinyl (-Docsorovicine chirley, its preparation and pharmaceutical preparations containing it
EP0683788B1 (fr)	1997-08-27	Derives de 3'-aziridino-anthracycline
US4853467A (en)	1989-08-01	Nitrogen containing derivatives of epipodophyllotoxin glucosides
AU7168100A (en)	2002-01-03	New 12,13-(pyranosyl)-indolo(2,3-a)pyrrolo(3,4-c)carbazole and 12,13-pyranosyl)-furo(3,4-c)indolo(2,3-a)carbazole compounds, a process for their preparation and pharmaceutical compositions containing them
EP0683787B1 (fr)	1997-09-10	Derives de 4'-o-sulfonyl-anthracycline
EP0475071A1 (fr)	1992-03-18	2-acyloxy-4-morpholinyl anthracycline
US6258786B1 (en)	2001-07-10	13-dihydro-3′ aziridino anthracyclines
EP1395599B1 (fr)	2005-08-10	Derives antitumoraux de l'acide sulphonique-14 de glycosides d'anthracyclines
JPH0586800B2 (fr)	1993-12-14
CA1075685A (fr)	1980-04-15	Synthese de 3',4'-didesoxykanamycine b
JPH03193798A (ja)	1991-08-23	アンスラサイクリン類、その製法及びそれを含有する医薬
GB2287463A (en)	1995-09-20	Bis-anthracycline derivatives
AU1919800A (en)	2000-06-13	Benzylmaltotriosides as inhibitors of smooth muscle cell proliferation