BG60535B2 - Нови морфолинови производни на даунорубицина и на доксорубицина - Google Patents

Нови морфолинови производни на даунорубицина и на доксорубицина Download PDF

Info

Publication number: BG60535B2
Authority: BG; Bulgaria
Prior art keywords: doxorubicin; methoxy; daunorubicin; morpholinyl; formula
Prior art date: 1985-03-22

Application number

BG098531A

Other languages

Bulgarian (bg)

English (en)

Inventor

Alberto Bargiotti

Pierangelo Zini

Sergio Penco

Fernando Giuliani

Original Assignee

Farmitalia Carlo Erba S.P.A.

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.)

1985-03-22

Filing date

1994-02-23

Publication date

1995-07-28

1994-02-23 Application filed by Farmitalia Carlo Erba S.P.A. filed Critical Farmitalia Carlo Erba S.P.A.

1995-07-28 Publication of BG60535B2 publication Critical patent/BG60535B2/bg

Links

150000002780 morpholines Chemical class 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 31
229930182470 glycoside Natural products 0.000 claims abstract description 16
238000002360 preparation method Methods 0.000 claims abstract description 16
150000002338 glycosides Chemical class 0.000 claims abstract description 15
238000000034 method Methods 0.000 claims abstract description 15
239000000203 mixture Substances 0.000 claims abstract description 14
229940045799 anthracyclines and related substance Drugs 0.000 claims abstract description 13
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 claims description 79
229960004679 doxorubicin Drugs 0.000 claims description 31
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 claims description 21
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 claims description 20
229960000975 daunorubicin Drugs 0.000 claims description 20
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 18
239000000243 solution Substances 0.000 claims description 17
150000003839 salts Chemical class 0.000 claims description 15
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
-1 2-methoxy-4-morpholinyl Chemical group 0.000 claims description 8
ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 5
125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
238000000746 purification Methods 0.000 claims description 4
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 3
239000002253 acid Substances 0.000 claims description 3
229910052783 alkali metal Inorganic materials 0.000 claims description 3
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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 claims description 2
150000001299 aldehydes Chemical class 0.000 claims description 2
239000003242 anti bacterial agent Substances 0.000 claims description 2
239000007864 aqueous solution Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
239000003937 drug carrier Substances 0.000 claims description 2
239000003480 eluent Substances 0.000 claims description 2
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 2
125000002757 morpholinyl group Chemical group 0.000 claims description 2
239000008194 pharmaceutical composition Substances 0.000 claims description 2
229910052708 sodium Inorganic materials 0.000 claims description 2
239000011734 sodium Substances 0.000 claims description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims 2
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235000008755 Lupinus mutabilis Nutrition 0.000 claims 1
235000019095 Sechium edule Nutrition 0.000 claims 1
239000002246 antineoplastic agent Substances 0.000 claims 1
230000003115 biocidal effect Effects 0.000 claims 1
238000003745 diagnosis Methods 0.000 claims 1
238000004128 high performance liquid chromatography Methods 0.000 claims 1
238000001356 surgical procedure Methods 0.000 claims 1
238000002560 therapeutic procedure Methods 0.000 claims 1
230000000259 anti-tumor effect Effects 0.000 abstract description 4
239000003814 drug Substances 0.000 abstract description 4
239000004480 active ingredient Substances 0.000 abstract 1
230000000144 pharmacologic effect Effects 0.000 abstract 1
208000032839 leukemia Diseases 0.000 description 10
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 6
230000015572 biosynthetic process Effects 0.000 description 5
238000002844 melting Methods 0.000 description 5
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238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 5
238000003786 synthesis reaction Methods 0.000 description 5
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 4
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
241000699670 Mus sp. Species 0.000 description 4
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 description 4
NAALWFYYHHJEFQ-ZASNTINBSA-N (2s,5r,6r)-6-[[(2r)-2-[[6-[4-[bis(2-hydroxyethyl)sulfamoyl]phenyl]-2-oxo-1h-pyridine-3-carbonyl]amino]-2-(4-hydroxyphenyl)acetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid Chemical compound N([C@@H](C(=O)N[C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C=1C=CC(O)=CC=1)C(=O)C(C(N1)=O)=CC=C1C1=CC=C(S(=O)(=O)N(CCO)CCO)C=C1 NAALWFYYHHJEFQ-ZASNTINBSA-N 0.000 description 3
MWWSFMDVAYGXBV-RUELKSSGSA-N Doxorubicin hydrochloride Chemical compound Cl.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 MWWSFMDVAYGXBV-RUELKSSGSA-N 0.000 description 3
231100000433 cytotoxic Toxicity 0.000 description 3
230000001472 cytotoxic effect Effects 0.000 description 3
229960003109 daunorubicin hydrochloride Drugs 0.000 description 3
229960002918 doxorubicin hydrochloride Drugs 0.000 description 3
229940079593 drug Drugs 0.000 description 3
230000000694 effects Effects 0.000 description 3
238000002474 experimental method Methods 0.000 description 3
238000000338 in vitro Methods 0.000 description 3
238000001727 in vivo Methods 0.000 description 3
230000003389 potentiating effect Effects 0.000 description 3
238000006722 reduction reaction Methods 0.000 description 3
229910000030 sodium bicarbonate Inorganic materials 0.000 description 3
235000017557 sodium bicarbonate Nutrition 0.000 description 3
230000001988 toxicity Effects 0.000 description 3
231100000419 toxicity Toxicity 0.000 description 3
YOFDHOWPGULAQF-MQJDWESPSA-N (7s,9s)-9-acetyl-6,7,9,11-tetrahydroxy-4-methoxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound C1[C@@](O)(C(C)=O)C[C@H](O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-MQJDWESPSA-N 0.000 description 2
208000008342 Leukemia P388 Diseases 0.000 description 2
241000699666 Mus <mouse, genus> Species 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
AYJRCSIUFZENHW-UHFFFAOYSA-L barium carbonate Chemical compound [Ba+2].[O-]C([O-])=O AYJRCSIUFZENHW-UHFFFAOYSA-L 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
238000003818 flash chromatography Methods 0.000 description 2
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 2
125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 2
239000000126 substance Substances 0.000 description 2
239000006188 syrup Substances 0.000 description 2
235000020357 syrup Nutrition 0.000 description 2
101100005766 Caenorhabditis elegans cdf-1 gene Proteins 0.000 description 1
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
241000219109 Citrullus Species 0.000 description 1
235000012828 Citrullus lanatus var citroides Nutrition 0.000 description 1
FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 description 1
SHZGCJCMOBCMKK-UHFFFAOYSA-N D-mannomethylose Natural products CC1OC(O)C(O)C(O)C1O SHZGCJCMOBCMKK-UHFFFAOYSA-N 0.000 description 1
YOFDHOWPGULAQF-UHFFFAOYSA-N Daunomycin-Aglycone Natural products C1C(O)(C(C)=O)CC(O)C2=C1C(O)=C1C(=O)C(C=CC=C3OC)=C3C(=O)C1=C2O YOFDHOWPGULAQF-UHFFFAOYSA-N 0.000 description 1
WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
101000573441 Homo sapiens Misshapen-like kinase 1 Proteins 0.000 description 1
SHZGCJCMOBCMKK-JFNONXLTSA-N L-rhamnopyranose Chemical compound C[C@@H]1OC(O)[C@H](O)[C@H](O)[C@H]1O SHZGCJCMOBCMKK-JFNONXLTSA-N 0.000 description 1
PNNNRSAQSRJVSB-UHFFFAOYSA-N L-rhamnose Natural products CC(O)C(O)C(O)C(O)C=O PNNNRSAQSRJVSB-UHFFFAOYSA-N 0.000 description 1
241000124008 Mammalia Species 0.000 description 1
102100026287 Misshapen-like kinase 1 Human genes 0.000 description 1
241000282339 Mustela Species 0.000 description 1
229940009456 adriamycin Drugs 0.000 description 1
230000029936 alkylation Effects 0.000 description 1
238000005804 alkylation reaction Methods 0.000 description 1
238000010171 animal model Methods 0.000 description 1
229940088710 antibiotic agent Drugs 0.000 description 1
PYMYPHUHKUWMLA-WDCZJNDASA-N arabinose Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)C=O PYMYPHUHKUWMLA-WDCZJNDASA-N 0.000 description 1
PYMYPHUHKUWMLA-UHFFFAOYSA-N arabinose Natural products OCC(O)C(O)C(O)C=O PYMYPHUHKUWMLA-UHFFFAOYSA-N 0.000 description 1
238000011888 autopsy Methods 0.000 description 1
WDIHJSXYQDMJHN-UHFFFAOYSA-L barium chloride Chemical compound [Cl-].[Cl-].[Ba+2] WDIHJSXYQDMJHN-UHFFFAOYSA-L 0.000 description 1
229910001626 barium chloride Inorganic materials 0.000 description 1
SRBFZHDQGSBBOR-UHFFFAOYSA-N beta-D-Pyranose-Lyxose Natural products OC1COC(O)C(O)C1O SRBFZHDQGSBBOR-UHFFFAOYSA-N 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
239000000460 chlorine Substances 0.000 description 1
229910052801 chlorine Inorganic materials 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
230000003013 cytotoxicity Effects 0.000 description 1
231100000135 cytotoxicity Toxicity 0.000 description 1
238000007865 diluting Methods 0.000 description 1
238000010828 elution Methods 0.000 description 1
NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 description 1
238000001914 filtration Methods 0.000 description 1
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
239000008103 glucose Substances 0.000 description 1
208000015181 infectious disease Diseases 0.000 description 1
229910003480 inorganic solid Inorganic materials 0.000 description 1
238000001990 intravenous administration Methods 0.000 description 1
IFZJXZDOECGKIH-UHFFFAOYSA-N methyl 2-(2-oxoethoxy)acetate Chemical compound COC(=O)COCC=O IFZJXZDOECGKIH-UHFFFAOYSA-N 0.000 description 1
239000012074 organic phase Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
239000000047 product Substances 0.000 description 1
239000011541 reaction mixture Substances 0.000 description 1
238000005932 reductive alkylation reaction Methods 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
238000000638 solvent extraction Methods 0.000 description 1
238000001228 spectrum Methods 0.000 description 1
239000007858 starting material Substances 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1
238000005406 washing Methods 0.000 description 1

Classifications

- 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
- 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
- A61P35/00—Antineoplastic agents
- A61P35/02—Antineoplastic agents specific for leukemia

Landscapes

Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Biochemistry (AREA)
Pharmacology & Pharmacy (AREA)
General Chemical & Material Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Engineering & Computer Science (AREA)
Medicinal Chemistry (AREA)
Biotechnology (AREA)
Genetics & Genomics (AREA)
Molecular Biology (AREA)
Hematology (AREA)
Oncology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Saccharide Compounds (AREA)

BG098531A 1985-03-22 1994-02-23 Нови морфолинови производни на даунорубицина и на доксорубицина BG60535B2 (bg)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
GB08507577A GB2172594B (en)	1985-03-22	1985-03-22	New morpholino derivatives of daunorubicin and doxorubicin

Publications (1)

Publication Number	Publication Date
BG60535B2 true BG60535B2 (bg)	1995-07-28

Family

ID=10576503

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
BG098531A BG60535B2 (bg)	1985-03-22	1994-02-23	Нови морфолинови производни на даунорубицина и на доксорубицина

Country Status (10)

Country	Link
US (1)	US4672057A (fr)
JP (1)	JPS61221194A (fr)
BE (1)	BE904431A (fr)
BG (1)	BG60535B2 (fr)
BR (1)	BR1100255A (fr)
CZ (1)	CZ419591A3 (fr)
DE (1)	DE3609052C2 (fr)
GB (1)	GB2172594B (fr)
HK (1)	HK37392A (fr)
MX (1)	MX9203114A (fr)

Families Citing this family (32)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3823224A1 (de) *	1988-07-08	1990-01-11	Behringwerke Ag	Morpholino-derivate der rhodomycine, verfahren zu ihrer herstellung und ihre verwendung
GB8905668D0 (en) *	1989-03-13	1989-04-26	Erba Carlo Spa	New 3'-(4-morpholinyl)-and 3'-(2-methoxy-4-morpholinyl)-anthracycline derivatives
US5304687A (en) *	1989-12-19	1994-04-19	Farmitalia Carlo Erba S.R.L.	Morpholinyl derivatives of doxorubicin and process for their preparation
DK0434960T3 (da) *	1989-12-19	1996-10-14	Pharmacia Spa	Chirale 1,5-diiod-2-methoxy- eller benzyloxymellemprodukter
GB9019934D0 (en) *	1990-09-12	1990-10-24	Erba Carlo Spa	2-hydroxy-and 2-acyloxy-4-morpholinyl anthracyclines
GB9019933D0 (en) *	1990-09-12	1990-10-24	Erba Carlo Spa	13-dihydro-3'-(2-alkoxy-4-morphlinyl)anthracyclines
GB9026491D0 (en) *	1990-12-05	1991-01-23	Erba Carlo Spa	Anthracycline-conjugates
US5776458A (en) *	1990-12-05	1998-07-07	Pharmacia & Upjohn S.P.A.	Anthracycline-conjugates
GB9028105D0 (en) *	1990-12-27	1991-02-13	Erba Carlo Spa	Process for the preparation of substituted benzofuran derivatives
GB9216962D0 (en) *	1992-08-11	1992-09-23	Erba Carlo Spa	Therapeutically active naphthalenesulfonic-pyrrolecarboxamido derivatives
GB9909925D0 (en) *	1999-04-29	1999-06-30	Pharmacia & Upjohn Spa	Combined preparations comprising anthracycline derivatives
AU767394C (en) *	1999-12-29	2005-04-21	Immunogen, Inc.	Cytotoxic agents comprising modified doxorubicins and daunorubicins and their therapeutic use
US20040038904A1 (en) *	2002-05-21	2004-02-26	Angela Ogden	Method of treating multiple sclerosis
EP1603575A2 (fr) *	2003-03-18	2005-12-14	Pharmacia Italia S.p.A.	Polytherapie contre des tumeurs comprenant l'administration de nemorubicine combinee a une radiotherapie
US20060198882A1 (en) *	2003-03-21	2006-09-07	Yechezkel Barenholz	Stable liposomes or micelles comprising a sphinolipid and a peg-lipopolymer
WO2006051549A2 (fr) *	2004-11-15	2006-05-18	Yissum Research Development Company Of The Hebrew University Of Jerusalem	Therapie combinee
JP4513765B2 (ja) *	2005-04-15	2010-07-28	日本ビクター株式会社	電気音響変換器
US20100069317A1 (en) *	2006-07-12	2010-03-18	Nerviano Medical Sciences S.R.L.	Crystalline nemorubicin hydrochloride
US20100104566A1 (en) *	2007-01-29	2010-04-29	Nerviano Medical Sciences S.R.L.	Antitumor combination comprising a morpholinyl anthracycline and an antibody
JP5302300B2 (ja)	2007-05-11	2013-10-02	ネルビアーノ・メデイカル・サイエンシーズ・エツセ・エルレ・エルレ	アンスラサイクリンの医薬組成物
WO2009016072A2 (fr) *	2007-08-02	2009-02-05	Nerviano Medical Sciences S.R.L.	Dérivé de la morpholinyle anthracycline combiné à des inhibiteurs de protéine kinases
EP2240495B1 (fr)	2008-02-01	2015-07-15	Genentech, Inc.	Métabolite de némorubicine et réactifs analogues, conjugués anticorps-médicament et procédés
US20110021517A1 (en) *	2008-02-26	2011-01-27	Nerviano Medical Sciences S.R.L.	Antitumor combination comprising a morpholinyl anthracycline derivative and demethylating agents
AU2009270988A1 (en)	2008-07-15	2010-01-21	Genentech, Inc.	Anthracycline derivative conjugates, process for their preparation and their use as antitumor compounds
JP2013530993A (ja)	2010-07-02	2013-08-01	アンジオケムインコーポレーテッド	治療用コンジュゲートのための短く且つｄ−アミノ酸を含有するポリペプチドおよびその使用
KR20190120439A (ko)	2010-11-08	2019-10-23	제넨테크, 인크.	피하 투여용 항―ｉｌ―6 수용체 항체
KR101897307B1 (ko)	2010-12-02	2018-09-10	네르비아노 메디칼 사이언시스 에스.알.엘.	모르폴리닐 안트라사이클린 유도체의 제조 방법
US8962577B2 (en)	2012-03-16	2015-02-24	The Johns Hopkins University	Controlled release formulations for the delivery of HIF-1 inhibitors
KR101640912B1 (ko) *	2014-07-03	2016-07-20	현대자동차주식회사	고온 저마찰성 코팅층 및 이의 제조방법
WO2016040825A1 (fr)	2014-09-12	2016-03-17	Genentech, Inc.	Intermédiaires disulfure d'anthracycline, conjugué anticorps-médicaments et procédés
EP4180061A1 (fr)	2021-11-10	2023-05-17	Nerviano Medical Sciences S.r.l.	Réactifs de liaison dérivés d'anthracycline, conjugués anticorps-médicament et procédés
WO2025168481A1 (fr)	2024-02-05	2025-08-14	Nerviano Medical Sciences S.R.L.	Dérivés d'imino-anthracycline et procédés

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
BE639897A (fr) *
US4464529A (en) *	1982-07-20	1984-08-07	Sri International	Analogues of morpholinyl daunorubicin and morpholinyl doxorubicin

1985
- 1985-03-22 GB GB08507577A patent/GB2172594B/en not_active Expired
1986
- 1986-03-17 US US06/839,936 patent/US4672057A/en not_active Expired - Lifetime
- 1986-03-18 DE DE3609052A patent/DE3609052C2/de not_active Expired - Lifetime
- 1986-03-18 BE BE0/216422A patent/BE904431A/fr not_active IP Right Cessation
- 1986-03-19 JP JP61059630A patent/JPS61221194A/ja active Granted
1991
- 1991-12-31 CZ CS914195A patent/CZ419591A3/cs unknown
1992
- 1992-05-28 HK HK373/92A patent/HK37392A/xx not_active IP Right Cessation
- 1992-06-22 MX MX9203114A patent/MX9203114A/es unknown
1994
- 1994-02-23 BG BG098531A patent/BG60535B2/bg unknown
1997
- 1997-04-10 BR BR1100255-7A patent/BR1100255A/pt active IP Right Grant

Also Published As

Publication number	Publication date
DE3609052A1 (de)	1986-09-25
JPH0482160B2 (fr)	1992-12-25
GB8507577D0 (en)	1985-05-01
MX9203114A (es)	1992-07-01
BE904431A (fr)	1986-07-16
US4672057A (en)	1987-06-09
BR1100255A (pt)	2002-04-02
HK37392A (en)	1992-06-04
GB2172594A (en)	1986-09-24
GB2172594B (en)	1988-06-08
DE3609052C2 (de)	1994-10-27
CZ419591A3 (en)	1993-03-17
JPS61221194A (ja)	1986-10-01

Publication	Publication Date	Title
BG60535B2 (bg)	1995-07-28	Нови морфолинови производни на даунорубицина и на доксорубицина
DE69710573T2 (de)	2002-10-31	Morpholinyl-anthracyclinderivate
US5304687A (en)	1994-04-19	Morpholinyl derivatives of doxorubicin and process for their preparation
RU2100366C1 (ru)	1997-12-27	Антрациклиновые гликозиды и их фармацевтически приемлемые кислотно-аддитивные соли, способ их получения, дииодопромежуточное соединение и способ его получения
US4585859A (en)	1986-04-29	Analogues of morpholinyl daunorubicin and morpholinyl doxorubicin
US5049549A (en)	1991-09-17	Rhodomycins with a modified carbohydrate unit
AU632102B2 (en)	1992-12-17	New 3'-(4-morpholinyl)- and 3'-(2-methoxy-4-morpholinyl)- anthracycline derivatives
RU2146261C1 (ru)	2000-03-10	8-фторантрациклины, способы их получения и содержащие их фармацевтические композиции
RU2144540C1 (ru)	2000-01-20	Антрациклиновые дисахариды, способ их получения и содержащие их фармацевтические композиции
US4870058A (en)	1989-09-26	14-Acyloxy-2'-halo-anthracycline anti-cancer antibiotics
AU749578B2 (en)	2002-06-27	13-dihydro-3'aziridino anthracyclines
US4772688A (en)	1988-09-20	14-acyloxy-2'-halo-anthracycline anti-cancer antibiotics
US4604381A (en)	1986-08-05	4-demethoxy-13-dihydrodaunorubicin and use thereof
DE3913759A1 (de)	1990-10-31	Zytostatisch wirksame rhodomycin-dimere
RU2081878C1 (ru)	1997-06-20	Антрациклин гликозид и способ его получения
EP0683787B1 (fr)	1997-09-10	Derives de 4'-o-sulfonyl-anthracycline
JPH01153694A (ja)	1989-06-15	新規４‐デメトキシアントラサイクリン誘導体
FI70414C (fi)	1986-09-19	Foerfarande foer framstaellning av nya 4'-jodderivater av antracyklinglykosider
KR0142228B1 (ko)	1998-06-15	신규 안트라사이클린 글리코시드유도체 및 그 제조방법
FI89496C (fi)	1993-10-11	Foerfarande foer framstaellning av 4-demetoxi-4-aminoantracykliner
JPS6260397B2 (fr)	1987-12-16
MXPA99011455A (en)	2000-06-01	13-dihydro-3'aziridino anthracyclines
JP2001039969A (ja)	2001-02-13	多剤耐性克服効果を有する新規化合物
GB2118932A (en)	1983-11-09	A daunorubicin derivative