US4303785A
Expired / Lapsed
US
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Antitumor anthracycline antibiotics
Assignee: Microbial Chemistry Research Foundation
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Filing: 1980-01-31
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Granted: 1981-12-01
•
Expires: 2000-01-31
Abstract
Abstract New anthracycline derivatives of adriamycin and daunomycin prepared by the etherification of the C-4' and/or C-14 hydroxyl groups of the starting material glycosides are found to be useful antimicrobial and antitumor agents.
Inventors
- 👤 Hamao Umezawa
- 👤 Tomio Takeuchi
- 👤 Hiroshi Naganawa
- 👤 Kuniaki Tatsuta
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-01 02:07
CPC Classifications
C; C07; C07H; C07H15/00; C07H15/20; C07H15/24; C07H15/252
Claims Analysis
Total Claims: 70
Claim 1
Independent Claim
75 words
An anthracycline glycoside of the formula ##STR35## wherein R 1 represents hydrogen, hydroxyl, tetrahydropyranyloxy, C 2 -C 7 alkanoyloxy or phenylacetyloxy and R 2 represents hydrogen, C 1 -C 8 alkyloxyethyl, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, with the provisos that (1) when R 1 is hydrogen or hydroxyl, R 2 is not hydrogen and (2) when R 1 is tetrahydropyranyloxy, R 2 is hydrogen or tetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 2
Dependent Claim
75 words
An anthracycline glycoside of the formula ##STR35## wherein R 1 represents hydrogen, hydroxyl, tetrahydropyranyloxy, C 2 -C 7 alkanoyloxy or phenylacetyloxy and R 2 represents hydrogen, C 1 -C 8 alkyloxyethyl, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, with the provisos that (1) when R 1 is hydrogen or hydroxyl, R 2 is not hydrogen and (2) when R 1 is tetrahydropyranyloxy, R 2 is hydrogen or tetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 3
Dependent Claim
58 words
An anthracycline glycoside of the formula ##STR36## wherein R 1 represents a hydrogen atom, a hydroxyl group or a tetrahydropyranyloxy group and R 2 represents a hydrogen atom or a tetrahydropyranyl group, providing that when R 1 is a hydrogen atom or a hydroxyl group, R 2 is a tetrahydropyranyl group, or a nontoxic acid addition salt thereof.
Claim 4
Dependent Claim
58 words
An anthracycline glycoside of the formula ##STR36## wherein R 1 represents a hydrogen atom, a hydroxyl group or a tetrahydropyranyloxy group and R 2 represents a hydrogen atom or a tetrahydropyranyl group, providing that when R 1 is a hydrogen atom or a hydroxyl group, R 2 is a tetrahydropyranyl group, or a nontoxic acid addition salt thereof.
Claim 5
Dependent Claim
21 words
An anthracycline glycoside of the formula ##STR37## wherein R 2 is a tetrahydropyranyl group, or a nontoxic acid addition salt thereof.
Claim 6
Dependent Claim
21 words
An anthracycline glycoside of the formula ##STR37## wherein R 2 is a tetrahydropyranyl group, or a nontoxic acid addition salt thereof.
Claim 7
Dependent Claim
19 words
The compound according to claim 3 which is 4'-O-tetrahydropyranyl daunomycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 8
Dependent Claim
19 words
The compound according to claim 3 which is 4'-O-tetrahydropyranyl daunomycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 9
Dependent Claim
26 words
The anthracycline glycoside of the formula ##STR38## wherein R 1 is a tetrahydropyranyloxy group and R 2 is hydrogen, or a nontoxic acid addition salt thereof.
Claim 10
Dependent Claim
26 words
The anthracycline glycoside of the formula ##STR38## wherein R 1 is a tetrahydropyranyloxy group and R 2 is hydrogen, or a nontoxic acid addition salt thereof.
Claim 11
Dependent Claim
24 words
An anthracycline glycoside of the formula ##STR39## wherein R 1 is tetrahydropyranyloxy and R 2 is tetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 12
Dependent Claim
24 words
An anthracycline glycoside of the formula ##STR39## wherein R 1 is tetrahydropyranyloxy and R 2 is tetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 13
Dependent Claim
18 words
The compound according to claim 7 which is 4',14-bis(O-tetrahydropyranyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 14
Dependent Claim
18 words
The compound according to claim 7 which is 4',14-bis(O-tetrahydropyranyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 15
Dependent Claim
21 words
An anthracycline glycoside of the formula ##STR40## wherein R 2 is a tetrahydropyranyl group, or a nontoxic acid addition salt thereof.
Claim 16
Dependent Claim
21 words
An anthracycline glycoside of the formula ##STR40## wherein R 2 is a tetrahydropyranyl group, or a nontoxic acid addition salt thereof.
Claim 17
Dependent Claim
19 words
The compound according to claim 10 which is 4'-O-tetrahydropyranyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 18
Dependent Claim
19 words
The compound according to claim 10 which is 4'-O-tetrahydropyranyl adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 19
Dependent Claim
80 words
An anthracycline glycoside of the formula ##STR41## wherein R 1 is a hydrogen atom, a hydroxyl group, an alkoanoyloxy group having from 2 to 7 carbon atoms inclusive or a phenylacetyloxy group and R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, with the proviso that when R 1 is hydrogen or hydroxyl, R 2 is not tetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 20
Dependent Claim
80 words
An anthracycline glycoside of the formula ##STR41## wherein R 1 is a hydrogen atom, a hydroxyl group, an alkoanoyloxy group having from 2 to 7 carbon atoms inclusive or a phenylacetyloxy group and R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, with the proviso that when R 1 is hydrogen or hydroxyl, R 2 is not tetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 21
Dependent Claim
47 words
An anthracycline glycoside according to claim 13 wherein R 1 is acetyloxy, isobutyloyloxy or phenylacetyloxy and R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 22
Dependent Claim
44 words
An anthracycline glycoside according to claim 13 wherein R 1 is hydrogen or hydroxyl and R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, 6-methoxytetrahydropyranyl, or 6-acetoxymethyltetrahydropyranyl, or a nonotoxic acid addition salt thereof.
Claim 23
Dependent Claim
18 words
The compound of claim 13 which is 14-O-acetyl-4'-O-tetrahydropyranyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 24
Dependent Claim
18 words
The compound of claim 13 which is 14-O-acetyl-4'-O-tetrahydropyranyl adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 25
Dependent Claim
18 words
The compound of claim 13 which is 14-O-isobutyloyl-4'-O-tetrahydropyranyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 26
Dependent Claim
18 words
The compound of claim 13 which is 14-O-isobutyloyl-4'-O-tetrahydropyranyl adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 27
Dependent Claim
18 words
The compound of claim 13 which is 14-O-phenylacetyl-4'-O-tetrahydropyranyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 28
Dependent Claim
18 words
The compound of claim 13 which is 14-O-phenylacetyl-4'-O-tetrahydropyranyl adriamycin (isomber b), or a nontoxic acid addition salt thereof.
Claim 29
Dependent Claim
16 words
The compound of claim 13 which is 14-O-acetyl-4'-O-tetrahydrofuranyl adriamycin, or a nontoxic acid addition salt thereof.
Claim 30
Dependent Claim
16 words
The compound of claim 13 which is 4'-O-tetrahydrofuranyl adriamycin, or a nontoxic acid addition salt thereof.
Claim 31
Dependent Claim
18 words
The compound of claim 13 which is 4'-O-tetrahydrofuranyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 32
Dependent Claim
18 words
The compound of claim 13 which is 4'-O-tetrahydrofuranyl adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 33
Dependent Claim
15 words
The compound of claim 13 which is 14-O-phenylacetyl-4'-O-(6-acetoxymethyltetrahydropyranyl)adriamycin, or a nonotoxic acid addition salt thereof.
Claim 34
Dependent Claim
15 words
The compound of claim 13 which is 4'-O-(6-acetoxymethyltetrahydropyranyl)adriamycin, or a nontoxic acid addition salt thereof.
Claim 35
Dependent Claim
15 words
The compound of claim 13 which is 14-O-phenylacetyl-4'-O-(1-ethyloxyethyl)adriamycin, or a nontoxic acid addition salt thereof.
Claim 36
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-ethyloxyethyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 37
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-ethyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 38
Dependent Claim
17 words
The compound of claim 13 which is 14-O-acetyl-4'-O-(1-butyloxyethyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 39
Dependent Claim
17 words
The compound of claim 13 which is 14-O-acetyl-4'-O-(1-butyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 40
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-butyloxyethyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 41
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-butyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 42
Dependent Claim
17 words
The compound of claim 13 which is 14-O-acetyl-4'-O-(1-isobutyloxyethyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 43
Dependent Claim
17 words
The compound of claim 13 which is 14-O-acetyl-4'-O-(1-isobutyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 44
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-isobutyloxyethyl)adriamycin (isomer a), or a nonotoxic acid addition salt thereof.
Claim 45
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-isobutyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 46
Dependent Claim
17 words
The compound of claim 13 which is 14-O-acetyl-4'-O-(6-methylheptyloxyethyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 47
Dependent Claim
17 words
The compound of claim 13 which is 14-O-acetyl-4'-O-(6-methylheptyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 48
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(6-methylheptyloxyethyl)adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 49
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(6-methylheptyloxyethyl)adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 50
Dependent Claim
18 words
The compound of claim 13 which is 14-O-acetyl-4'-O-cyclohexyloxyethyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 51
Dependent Claim
18 words
The compound of claim 13 which is 14-O-acetyl-4'-O-cyclohexyloxyethyl adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 52
Dependent Claim
18 words
The compound of claim 13 which is 4'-O-cyclohexyloxyethyl adriamycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 53
Dependent Claim
18 words
The compound of claim 13 which is 4'-O-cyclohexyloxyethyl adriamycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 54
Dependent Claim
15 words
The compound of claim 13 which is 4'-O-(tetrahydrofuranyl)daunomycin, or a nontoxic acid addition salt thereof.
Claim 55
Dependent Claim
15 words
The compound of claim 13 which is 4'-O-(6-acetoxymethyltetrahydropyranyl)daunomycin, or a nontoxic acid addition salt thereof.
Claim 56
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(6-methoxytetrahydropyranyl)daunomycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 57
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(6-methoxytetrahydropyranyl)daunomycin (isomber b), or a nontoxic acid addition salt thereof.
Claim 58
Dependent Claim
15 words
The compound of claim 13 which is 4'-O-(6-carbomethoxytetrahydropyranyl)daunomycin, or a nonotoxic acid addition salt thereof.
Claim 59
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-ethyloxyethyl)daunomycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 60
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-ethyloxyethyl)daunomycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 61
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-isobutyloxyethyl)daunomycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 62
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-isobutyloxyethyl)daunomycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 63
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-butyloxyethyl)daunomycin (isomer a), or a nontoxic acid addition salt thereof.
Claim 64
Dependent Claim
17 words
The compound of claim 13 which is 4'-O-(1-butyloxyethyl)daunomycin (isomer b), or a nontoxic acid addition salt thereof.
Claim 65
Dependent Claim
54 words
An anthracycline glycoside of the formula ##STR42## wherein R 3 is phenylacetyloxy or alkanoyloxy having from 2 to 7 carbon atoms inclusive and R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 66
Dependent Claim
54 words
An anthracycline glycoside of the formula ##STR42## wherein R 3 is phenylacetyloxy or alkanoyloxy having from 2 to 7 carbon atoms inclusive and R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, tetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 67
Dependent Claim
39 words
An anthracycline glycoside of the formula ##STR43## wherein R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, 6-methoxytetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 68
Dependent Claim
39 words
An anthracycline glycoside of the formula ##STR43## wherein R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, 6-methoxytetrahydropyranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 69
Dependent Claim
38 words
An anthracycline glycoside of the formula ##STR44## wherein R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
Claim 70
Dependent Claim
38 words
An anthracycline glycoside of the formula ##STR44## wherein R 2 is alkyloxyethyl in which the alkyl portion has from 1 to 8 carbon atoms inclusive, cyclohexyloxyethyl, tetrahydrofuranyl, 6-methoxytetrahydropyranyl, 6-carbomethoxytetrahydropyranyl or 6-acetoxymethyltetrahydropyranyl, or a nontoxic acid addition salt thereof.
References Cited (Backward Citations)
GB1003383A
Cited
US3616242A
Cited
US3590028A
Cited
US3803124A
Cited
US4020270A
Cited
US4025623A
Cited
US4012448A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-11-30 | 1985-06-01 | 1985-12-01 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-11-30 | 1989-06-01 | 1989-12-01 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-11-30 | 1993-06-01 | 1993-12-01 | $7700.00 | Window Closed / Lapsed |