CA1095028A - Anthracyclines - Google Patents

Anthracyclines

Info

Publication number: CA1095028A
Authority: CA; Canada
Prior art keywords: daunorubicin; desacetyl; trifluoroacetyl; keto; chloroform
Prior art date: 1976-07-13
Legal status (The legal status 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 status listed.): Expired

Application number

CA348,323A

Other languages

English (en)

Inventor

Sergio Penco

Francesco Angelucci

Federico Arcamone

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Pfizer Italia SRL

Original Assignee

Farmaceutici Italia 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.)

1976-07-13

Filing date

1980-03-24

Publication date

1981-02-03

1976-07-13 Priority claimed from GB28986/76A external-priority patent/GB1524468A/en

1980-03-24 Application filed by Farmaceutici Italia SpA filed Critical Farmaceutici Italia SpA

1980-03-24 Priority to CA348,323A priority Critical patent/CA1095028A/fr

1981-02-03 Application granted granted Critical

1981-02-03 Publication of CA1095028A publication Critical patent/CA1095028A/fr

Status Expired legal-status Critical Current

Links

229940045799 anthracyclines and related substance Drugs 0.000 title description 3
JQWHASGSAFIOCM-UHFFFAOYSA-M sodium periodate Chemical compound [Na+].[O-]I(=O)(=O)=O JQWHASGSAFIOCM-UHFFFAOYSA-M 0.000 claims abstract description 10
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims abstract description 8
238000000034 method Methods 0.000 claims abstract description 4
238000004519 manufacturing process Methods 0.000 claims abstract description 3
230000001590 oxidative effect Effects 0.000 claims abstract description 3
239000000126 substance Substances 0.000 claims 1
150000001875 compounds Chemical class 0.000 abstract description 14
206010028980 Neoplasm Diseases 0.000 abstract description 5
STQGQHZAVUOBTE-VGBVRHCVSA-N daunorubicin Chemical class 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 abstract description 5
239000000543 intermediate Substances 0.000 abstract 1
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 11
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 8
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
229960000975 daunorubicin Drugs 0.000 description 7
239000000243 solution Substances 0.000 description 7
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 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 4
239000012279 sodium borohydride Substances 0.000 description 4
229910000033 sodium borohydride Inorganic materials 0.000 description 4
229910052938 sodium sulfate Inorganic materials 0.000 description 4
235000011152 sodium sulphate Nutrition 0.000 description 4
239000002904 solvent Substances 0.000 description 4
QAEDZJGFFMLHHQ-UHFFFAOYSA-N trifluoroacetic anhydride Chemical compound FC(F)(F)C(=O)OC(=O)C(F)(F)F QAEDZJGFFMLHHQ-UHFFFAOYSA-N 0.000 description 4
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 3
OAIVIYSBZFEOIU-UHFFFAOYSA-N chloroform;propan-2-one Chemical compound CC(C)=O.ClC(Cl)Cl OAIVIYSBZFEOIU-UHFFFAOYSA-N 0.000 description 3
229960004679 doxorubicin Drugs 0.000 description 3
239000012074 organic phase Substances 0.000 description 3
238000004809 thin layer chromatography Methods 0.000 description 3
PILBYTNNIUDJPF-UHFFFAOYSA-N 10-(4-amino-5-hydroxy-6-methyloxan-2-yl)oxy-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione Chemical compound C1=2C(O)=C3C(=O)C=4C(OC)=CC=CC=4C(=O)C3=C(O)C=2CC(O)CC1OC1CC(N)C(O)C(C)O1 PILBYTNNIUDJPF-UHFFFAOYSA-N 0.000 description 2
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 2
208000028018 Lymphocytic leukaemia Diseases 0.000 description 2
241000699670 Mus sp. Species 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
239000002253 acid Substances 0.000 description 2
125000003277 amino group Chemical group 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
230000000694 effects Effects 0.000 description 2
238000002474 experimental method Methods 0.000 description 2
239000000284 extract Substances 0.000 description 2
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 2
229910000041 hydrogen chloride Inorganic materials 0.000 description 2
239000002054 inoculum Substances 0.000 description 2
208000003747 lymphoid leukemia Diseases 0.000 description 2
230000004083 survival effect Effects 0.000 description 2
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 1
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
HJEZFVLKJYFNQW-FKKRWUELSA-N 13-dihydrodaunorubicin 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 HJEZFVLKJYFNQW-FKKRWUELSA-N 0.000 description 1
XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 description 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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
229910052783 alkali metal Inorganic materials 0.000 description 1
150000001340 alkali metals Chemical class 0.000 description 1
230000002927 anti-mitotic effect Effects 0.000 description 1
239000007864 aqueous solution Substances 0.000 description 1
LRHPLDYGYMQRHN-UHFFFAOYSA-N butyl alcohol Substances CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
238000006243 chemical reaction Methods 0.000 description 1
239000003638 chemical reducing agent Substances 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
125000001309 chloro group Chemical group Cl* 0.000 description 1
238000004587 chromatography analysis Methods 0.000 description 1
IQFVPQOLBLOTPF-HKXUKFGYSA-L congo red Chemical compound [Na+].[Na+].C1=CC=CC2=C(N)C(/N=N/C3=CC=C(C=C3)C3=CC=C(C=C3)/N=N/C3=C(C4=CC=CC=C4C(=C3)S([O-])(=O)=O)N)=CC(S([O-])(=O)=O)=C21 IQFVPQOLBLOTPF-HKXUKFGYSA-L 0.000 description 1
229960003109 daunorubicin hydrochloride Drugs 0.000 description 1
150000002009 diols Chemical class 0.000 description 1
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
239000003814 drug Substances 0.000 description 1
229930182470 glycoside Natural products 0.000 description 1
150000002338 glycosides Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000000203 mixture Substances 0.000 description 1
230000003647 oxidation Effects 0.000 description 1
238000007254 oxidation reaction Methods 0.000 description 1
KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
238000002360 preparation method Methods 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
239000012047 saturated solution Substances 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
RMAQACBXLXPBSY-UHFFFAOYSA-N silicic acid Chemical compound O[Si](O)(O)O RMAQACBXLXPBSY-UHFFFAOYSA-N 0.000 description 1
235000012239 silicon dioxide Nutrition 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000725 suspension Substances 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
238000005583 trifluoroacetylation reaction Methods 0.000 description 1

Landscapes

Saccharide Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

CA348,323A 1976-07-13 1980-03-24 Anthracyclines Expired CA1095028A (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA348,323A CA1095028A (fr)	1976-07-13	1980-03-24	Anthracyclines

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
GB28986/76A GB1524468A (en)	1976-07-13	1976-07-13	Anthracylines
GB28986/76		1976-07-13
CA282,526A CA1091225A (fr)	1976-07-13	1977-07-12	Anthracyclines
CA348,323A CA1095028A (fr)	1976-07-13	1980-03-24	Anthracyclines

Publications (1)

Publication Number	Publication Date
CA1095028A true CA1095028A (fr)	1981-02-03

Family

ID=27165176

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA348,323A Expired CA1095028A (fr)	1976-07-13	1980-03-24	Anthracyclines

Country Status (1)

Country	Link
CA (1)	CA1095028A (fr)

1980
- 1980-03-24 CA CA348,323A patent/CA1095028A/fr not_active Expired

Publication	Publication Date	Title
CA1239639A (fr)	1988-07-26	Derive epimere d'azahomoerythromycine a et intermediaires
CA1061335A (fr)	1979-08-28	Procede de preparation de glycosides oncolytiques
JPS63313796A (ja)	1988-12-21	４−デメントキシ−４−アミノ−アントラサイクリン類
Fuchs et al.	1979	Synthesis and antitumor activity of sugar-ring hydroxyl analogs of daunorubicin
EP0051280B1 (fr)	1984-07-11	Dérivés glycosidiques d'anthracyclines, méthode pour leur préparation, dérivés intermédiaires et leur préparation et compositions pharmaceutiques
JP2516769B2 (ja)	1996-07-24	新規なアントラサイクリン
EP0024727B1 (fr)	1982-05-26	Anthracycline glycosides, procédés pour leur préparation et composition pharmaceutique les contenant
EP0199920B1 (fr)	1988-08-17	Anthracyclines à activité antitumorale
CA1091225A (fr)	1980-12-09	Anthracyclines
EP0022515B1 (fr)	1983-08-03	Anthracycline glycosides, procédé pour leur préparation et composition thérapeutique les contenant
US4839346A (en)	1989-06-13	Antitumor anthracycline glycosides, intermediates thereof, and composition and use thereof
CA1128503A (fr)	1982-07-27	Procede de preparation d'anthracyclines substituees antitumorales
CA1095028A (fr)	1981-02-03	Anthracyclines
GB2144744A (en)	1985-03-13	4'-halo-anthracycline glycosides
US5045534A (en)	1991-09-03	4-demethoxy-4'-amino-4'-deoxy-anthracycline derivatives
DE3905431A1 (de)	1989-09-07	Neue 4-demethyl-4-0-(p-fluorobenzolsulfonyl)anthracyclinglycoside
CA1091657A (fr)	1980-12-16	Nouvel agent anti-tumeur, hydrochlorure de 9- desacetyl-9 ethylene oxyde daunorubicine
US3970643A (en)	1976-07-20	5"-Amino-3',5"-dideoxybutirosin A and derivatives
KR920000620B1 (ko)	1992-01-17	신규 안트라사이클린 글리코사이드 유도체
CA1177828A (fr)	1984-11-13	6"-desoxydibekacine, 4", 6"-didesoxydibekacine et derives 1-n-aminoacyles; preparation de ces nouveaux composes
CA1188684A (fr)	1985-06-11	Anthracycline glycosides iodes en 4'
IE49422B1 (en)	1985-10-02	Antitumor glycosides
CA1250284A (fr)	1989-02-21	Derive d'azahomoerythromycine epimere antibacterien et methode de production dudit derive
GB2034707A (en)	1980-06-11	Anthracycline glycosides
US3983102A (en)	1976-09-28	Process for preparing 5"-amino-4',5"-dideoxybutirosin A

Legal Events

Date	Code	Title	Description
1998-02-03	MKEX	Expiry