IE930184L - 4-demethoxy-4-amino-anthracyclines - Google Patents
4-demethoxy-4-amino-anthracyclinesInfo
- Publication number
- IE930184L IE930184L IE930184A IE930184A IE930184L IE 930184 L IE930184 L IE 930184L IE 930184 A IE930184 A IE 930184A IE 930184 A IE930184 A IE 930184A IE 930184 L IE930184 L IE 930184L
- Authority
- IE
- Ireland
- Prior art keywords
- demethoxy
- daunomycinone
- amino
- formula
- deoxy
- Prior art date
Links
- 229940045799 anthracyclines and related substance Drugs 0.000 title description 6
- 238000000034 method Methods 0.000 claims description 14
- ZUFQFGSMHXKORU-UHFFFAOYSA-N 9-acetyl-6,7,9,11-tetrahydroxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C(O)=C1C(O)CC(C(=O)C)(O)CC1=C2O ZUFQFGSMHXKORU-UHFFFAOYSA-N 0.000 claims description 12
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 claims description 8
- 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 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 6
- 239000007864 aqueous solution Substances 0.000 claims description 5
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 235000010288 sodium nitrite Nutrition 0.000 claims description 4
- 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 claims description 2
- 150000001989 diazonium salts Chemical class 0.000 claims description 2
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- GQZXNSPRSGFJLY-UHFFFAOYSA-N hydroxyphosphanone Chemical compound OP=O GQZXNSPRSGFJLY-UHFFFAOYSA-N 0.000 claims 1
- 229940046817 hypophosphorus acid Drugs 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229930182470 glycoside Natural products 0.000 description 4
- 150000002338 glycosides Chemical class 0.000 description 4
- 238000002360 preparation method Methods 0.000 description 4
- 150000003839 salts Chemical class 0.000 description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 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 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 3
- 125000003277 amino group Chemical group 0.000 description 3
- 229960000908 idarubicin Drugs 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 3
- XYDJGVROLWFENK-YBTHPKLGSA-N (7s,9s)-9-acetyl-4,6,7,9,11-pentahydroxy-8,10-dihydro-7h-tetracene-5,12-dione Chemical compound O=C1C2=C(O)C=CC=C2C(=O)C2=C1C(O)=C1[C@@H](O)C[C@@](C(=O)C)(O)CC1=C2O XYDJGVROLWFENK-YBTHPKLGSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 230000031709 bromination Effects 0.000 description 2
- 238000005893 bromination reaction Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 239000002904 solvent Substances 0.000 description 2
- 238000003756 stirring 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
- OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 1
- -1 4-fluoro-benzensulfonyl group Chemical group 0.000 description 1
- BFXHJFKKRGVUMU-UHFFFAOYSA-N 4-fluorobenzenesulfonyl chloride Chemical compound FC1=CC=C(S(Cl)(=O)=O)C=C1 BFXHJFKKRGVUMU-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- TWCMVXMQHSVIOJ-UHFFFAOYSA-N Aglycone of yadanzioside D Natural products COC(=O)C12OCC34C(CC5C(=CC(O)C(O)C5(C)C3C(O)C1O)C)OC(=O)C(OC(=O)C)C24 TWCMVXMQHSVIOJ-UHFFFAOYSA-N 0.000 description 1
- PLMKQQMDOMTZGG-UHFFFAOYSA-N Astrantiagenin E-methylester Natural products CC12CCC(O)C(C)(CO)C1CCC1(C)C2CC=C2C3CC(C)(C)CCC3(C(=O)OC)CCC21C PLMKQQMDOMTZGG-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- PFOARMALXZGCHY-UHFFFAOYSA-N homoegonol Natural products C1=C(OC)C(OC)=CC=C1C1=CC2=CC(CCCO)=CC(OC)=C2O1 PFOARMALXZGCHY-UHFFFAOYSA-N 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 238000006140 methanolysis reaction Methods 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- CQLFBEKRDQMJLZ-UHFFFAOYSA-M silver acetate Chemical compound [Ag+].CC([O-])=O CQLFBEKRDQMJLZ-UHFFFAOYSA-M 0.000 description 1
- 229940071536 silver acetate Drugs 0.000 description 1
- 229910052938 sodium sulfate Inorganic materials 0.000 description 1
- 235000011152 sodium sulphate Nutrition 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Saccharide Compounds (AREA)
Description
4-DEMETHOXY-4-AMINO-ANTHRACYCLINES The invention relates to a process for preparing intermediates for use in the preparation of anthracycline glycosides.
The intermediates may be used to prepare e.g. anthracycline glycosides having the general formula (I): wherein Rx represents a hydrogen atom or a hydroxyl group, one of Ra and R~ represents a hydrogen atom and the other of R2 and r3 represents a hydrogen atom or a hydroxyl group, and their pharmaceutically acceptable addition salts.
B 0 o 2 7 The glycosides of formula (I) and their pharmaceutically acceptable addition salts are prepared by a process in which the starting material is a daunomycinone derivative of formula (II): 21 wherein the 4-amino group is protected. This process is described in Irish application no: 1171/88 from which the present application is divided.
The daunomycinone derivative of formula (II) and protected derivatives thereof wherein the 4-amino group is protected . may be prepared by a process which comprises: 5 (a) removing by hydrogenolysis the 7a-hydroxyl group of carminomycinone of formula (V): H 6H (b) reacting the resultant 4-demethyl-7-deoxy-daunomycinone of formula (VI): VI with 4-fluorobenzensulfonyl chloride in the presence of N,N-diisopropylethylamine and a catalytic amount of 4-dimethylaminopyridine; (c) reacting the resultant 4-demethoxy-4-0-5 I4-fluorobenzensulfonyl]-7-deoxy-daunomycinone of formula (VII): VII with benzylamine; (d) removing the benzyl group from the resultant 4-demethoxy-4-benzylamino-7-deoxy-daunomycinone of formula (VIII): VIII by catalytic hydrogenation; (e) protecting the 4-amino group of the resultant 4-demethoxy-4-amino-7-deoxy-daunomycinone of formula (IX): (f) reintroducing the 7a-hydroxy group into the resultant compound of formula (X): - G - wherein X' represents the amino protecting group, thereby obtaining a protected derivative of formula (XI) of a daunomycinone derivative of formula (II): XI wherein X' is defined above; and (g) if desired, removing the 4-amino protecting group from the protected derivative of formula (XI), thereby obtaining the daunomycinone derivative of formula (II): II This process is illustrated in Scheme I below. The starting compound for the process is the natural carminomycinone (V). The sulfonylation reaction, step (b), leads only the substituted C-4-O-sulfonyl derivative (VII), 5 leaving the C-6-0H and C-11-0H unaffected. It should be stressed that this unexpected selectivity has been achieved only under the conditions described herein.
Reaction (c) is a new one in anthracycline chemistry, probably due to the withdrawing effect both of 10 the guinone moiety and of the 4-fluoro-benzensulfonyl group at the position C-4. Preferably, the reaction is effected in tetrahydrofuran at room temperature. Step (e) is preferably effected with trifluoroacetic anhydride. Preferably, therefore Xr represents a trifluoroacetyl group 15 in formulae (X) and (XI). Step (f) may be performed according to the method described by £.M. Hong et al., Can.J.Chem., 51, 446 (1973). Preferably, it is effected by protecting the 13-keto group of a 4-demethoxy-4-(protected - 8 -Scheme I (a) H 6h VI (c) (d) (f) IX XII COCF jNH A 6H XIII (g) amino)-7-deoxy-daunomycinone compound of formula (XII): XII by treatment with ethylene glycol; brominating the resultant compound at the 7-position; and hydrolysing the 7-bromo and 13-ketal groups to give 4-demethoxy-4-N-tri-fluoroacetamido-daunomycinone of formula (XIII): XIII Bromination is generally achieved by treatment with bromine or N-bromosuccinimide in the presence of 2,2'-azo-bis(iso-butyronitrile).
The intermediates of formula (II) and (IX) are also useful for the preparation of 4-demethoxy-7-deoxy-daunomycinone or 4-demethoxy-daunomycinone. 4-Demethoxy-7-deoxy-daunomycinone can be converted into 4-demethoxy-daunomycinone. Further antitumor anthracycline glycosides can be prepared from 4-demethoxy-daunomycinone.
According to the present invention, there therefore is provided a suitable process for preparing 4-demethoxy-7-deoxy-daunomycinone or 4-demethoxy-daunomycinone of formula (XIV): XIV in which R4 represents hydrogen or hydroxy, which process comprises diazotising the 4-amino group of 4-demethoxy-4-amino-7-deoxy-daunomycinone or 4-demethoxy-4-amino-daunomycinone of formula (XV): XV in which R4 is as defined above, and reducing under mild conditions the diazonium compound thus-formed.
Anthracyclinones bearing an amino group at position C-4 are therefore transformed into their corresponding desamino derivatives. The starting compounds are 4-demethoxy-4-amino-7-deoxy-daunomycinone (IX(XVa, R - H)) and 4-demethoxy-4-amino-daunomycinone (IX (XVb, R-OH)). The removal of the 4-amino group, via diazotisation and mild reduction, leads to the well known 4-demethoxy-7-deoxy-daunomycinone (XlVa, R«H) or 4-demethoxy-daunomycinone (XlVb, R-OH). As shown in Scheme II, diazotisation is preferably effected using aqueous sodium nitrite. The mild reduction is preferably effected using hypophosphorous acid.
Scheme II 1) aq H&H02 2) Hypophocphor acid Compound XVa in which R4-H can be easily transformed into compound XVb in which R4»OH by standard methods. Preferably, the 4-demethoxy-4-amino-7-deoxy-daunomycinone (XVa) or 4-demethoxy-4-amino-daunomycinone (XVb), dissolved in aqueous 37% hydrochloric acid, is reacted at a temperature of from 0° to 5°C and for 1 hour with an aqueous solution of sodium nitrite and, subsequently, for 5 hours at room temperature under vigorous stirring with an aqueous solution of 50% hypophosphorous acid, the reaction mixture is extracted with methylene dichloride and the solvent is removed under reduced pressure. converted into 4-demethoxy-daunomycinone (XlVb) by introducing a hydroxy group at the 7-position. This can be achieved according to the invention by bromination of the 7-position, for example by bromine or N-bromo-succinimide (NBS), followed by treatment with 4-Demethoxy-7-deoxy-daunomycinone (XlVa) may be alkali or with silver acetate or methanolysis of the acetate thus formed. 4-Demethoxy-daunomycinone (XlVb) is the aglycone moiety of the useful antitumor drug 4-demethoxy- daunorubicin (XVI). Accordingly, the present invention further provides a process for preparing 4-demethoxy-daunorubicin of formula (XVI): or a pharmaceutically acceptable salt thereof; which process comprises reacting 4-demethoxy-daunomycinone, which is represented by formula (XIV) in which R4 is hydroxy and which has been prepared from 4-demethoxy-4-amino-daunomycinone by a process according to the invention, with an appropriate sugar derivative and, if desired, converting the 4-demethoxy-daunorubicin thus-obtained into a pharmaceutically acceptable salt thereof.
The sugar derivative may have the formula (XVII): Hal wherein Bal represents a halogen atom, R4 represents a protected hydroxy group and R7 represents a protected amino group. The protecting groups are removed after reaction with 4-demethoxy-daunomycinone. Preferably Hal is a chlorine atom. The hydroxy group may be protected by a trifluoroacetyl group. The amino group may be protected by a trifluoroacetyl group also. - 15 Example 1 Preparation of 4-demethoxv-7-deoxy-daunomycinone (XlVa) 1.78 g (5 mmol) of 4-demethoxy-4-amino-7-deoxy-daunomycinone (IX) dissolved with 75 ml of aqueous 37% hydrochloric acid, are cooled at 0-5°C and 75 ml of an aqueous solution containing 0.6 g of sodium nitrite is added. The mixture is stirred for one hour at 0-5°C. Then 75 ml of an aqueous solution of 50% hypophosphorous acid is added and the mixture is kept at room temperature for five hours under vigorous stirring.
The solution is diluted with 200 ml of water and extracted with methylene dichloride. The organic layer is separated off, dried over anhydrous sodium sulphate and the solvent is removed under reduced pressure to give a quantitative yield (1.7 g) of 4-demethoxy-7-deoxy- 1 daunomycinone (XlVa), analytically compared with a standard i sample.
Example 2 preparation of 4-demethoxy-daunomycinone (XlVb) 1.86 g (5 mmol) of 4-demethoxy-4-amino-daunomycinone (II) 1 are transformed into the corresponding 4-demethoxy-daunomycinone (XlVb) following the method above described. Yield: 1.8 g of compound XlVb analytically compared with a standard sample.
Claims (4)
1. A process for preparing 4-demethoxy-7- deoxy daunomycinone or 4-demethoxy-daunomycinone of formula XIV XIV in which R4 is hydrogen or hydroxy which process comprises diazotising the 4-amino group of 4-demethoxy-4-amino-7-daunomycinone or 4-demethoxy-4-amino-daunomycinone of formula XV 0 OH 10 I ^ L JL^JL J yja XV in which R4 is defined above, and reducing under mild conditions the diazonium compound thus-formed.
2. A process according to claim 1 in which the diazotisation comprises treating the compound of formula XV 15 with an aqueous solution of sodium nitrite.
3. A process according to claim 1 or 2 in which the reduction is carried out by reaction using hypophosphorus acid. - 18 -
4. A process according to any one of claims 1 to 3 substantially as described herein with reference to the Examples. TOMKINS & CO.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IE930184A IE80627B1 (en) | 1987-04-21 | 1988-04-19 | 4-Demethoxy-4-Amino-Anthracyclines |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB878709353A GB8709353D0 (en) | 1987-04-21 | 1987-04-21 | 4-demethoxy-4-amino-anthracyclines |
| GB888803302A GB8803302D0 (en) | 1988-02-12 | 1988-02-12 | Conversion of 4-demethoxy-4-amino anthracyclinones into 4-demethoxy-anthracyclinones |
| IE117188A IE63510B1 (en) | 1987-04-21 | 1988-04-19 | 4-Demethoxy-4- amino-anthracyclines |
| IE930184A IE80627B1 (en) | 1987-04-21 | 1988-04-19 | 4-Demethoxy-4-Amino-Anthracyclines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IE930184L true IE930184L (en) | 1988-10-21 |
| IE80627B1 IE80627B1 (en) | 1998-10-21 |
Family
ID=27263393
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IE930184A IE80627B1 (en) | 1987-04-21 | 1988-04-19 | 4-Demethoxy-4-Amino-Anthracyclines |
Country Status (1)
| Country | Link |
|---|---|
| IE (1) | IE80627B1 (en) |
-
1988
- 1988-04-19 IE IE930184A patent/IE80627B1/en not_active IP Right Cessation
Also Published As
| Publication number | Publication date |
|---|---|
| IE80627B1 (en) | 1998-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP0426653B1 (en) | 4-demethoxy-4-amino-anthracyclines | |
| US4345070A (en) | Process for the preparation of 4'-deoxy-daunorubicin and 4'-deoxy-doxorubicin | |
| EP0051280B1 (en) | Anthracycline glycosides, process for the preparation thereof, intermediate compounds and their preparation and pharmaceutical compositions | |
| EP0254484B1 (en) | 6-amino anthracyclines, process for their preparation and use thereof | |
| JP2516769B2 (en) | New anthracyclines | |
| EP0199920B1 (en) | New antitumor anthracyclines | |
| EP0381989B1 (en) | New 4'-epi-4'-amino anthracyclines | |
| IE930184L (en) | 4-demethoxy-4-amino-anthracyclines | |
| AU632102B2 (en) | New 3'-(4-morpholinyl)- and 3'-(2-methoxy-4-morpholinyl)- anthracycline derivatives | |
| EP0475071B1 (en) | 2-acyloxy-4-morpholinyl anthracycline | |
| WO1990001490A1 (en) | 4-substituted anthracyclinones and anthracycline glycosides and their preparation | |
| JPH0778073B2 (en) | Nitroanthracycline, process for its production and use thereof | |
| US5412081A (en) | New 4'-epi-4'-amino anthracyclines | |
| CA1131218A (en) | Process for the preparation of new antitumor glycosides | |
| KR950013771B1 (en) | Method for preparing 14-chlorodaunomycin and method for preparing (2 "R) -4'-O-tetrahydropyranyl adriamycin | |
| GB2034707A (en) | Anthracycline glycosides | |
| SI8910940A8 (en) | Process for obtaining 4-demethoxy-antracyclinones | |
| IL104975A (en) | 4-Demethoxydoxorubicin- and daunomycin-4- carboxylic acids, esters thereof, their preparation and pharmaceutical compositions containing them |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MM4A | Patent lapsed |