US4263428A
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US
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Bis-anthracycline nucleic acid function inhibitors and improved method for administering the same
Assignee: University of California, San Diego
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Filing: 1979-02-23
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Granted: 1981-04-21
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Expires: 1999-02-23
Abstract
Abstract A new group of compounds having an enhanced ability to inhibit nucleic acid functions have been prepared. These drugs are bis-anthracyclines wherein two anthracycline molecules are linked through their C-13 carbon atoms by amino and/or hydroxy-dicarboxylic acids and their derivatives to form the bis-compounds. Such bis-anthracyclines may be even more effectively delivered to selected sites in a mammalian organism by incorporating the same within uniformly sized liposomes.
Inventors
- 👤 Martin A. Apple
- 👤 C. Anthony Hunt
- 👤 Hiroaki Yanagisawa
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 02:27
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K9/00; A61K9/10; A61K9/127; A61K9/1277; A61P; A61P35/00; C; C07; C07H; C07H15/00; C07H15/20; C07H15/24; C07H15/252
Claims Analysis
Total Claims: 28
Claim 1
Independent Claim
33 words
As compositions of matter, bis-anthracycline compounds wherein two anthracycline moieties are linked through their respective C-13 carbon atoms by a cross-linking substituent, said cross-linking substituent being hydroxy-dicarboxylic acid hydrazones or amino-dicarboxylic acid hydrazones.
Claim 2
Dependent Claim
33 words
As compositions of matter, bis-anthracycline compounds wherein two anthracycline moieties are linked through their respective C-13 carbon atoms by a cross-linking substituent, said cross-linking substituent being hydroxy-dicarboxylic acid hydrazones or amino-dicarboxylic acid hydrazones.
Claim 3
Dependent Claim
16 words
The compounds of claim 1, wherein both of said anthracycline moieties are either daunorubicin or adriamycin.
Claim 4
Dependent Claim
33 words
As compositions of matter, bis-anthracycline compounds wherein two anthracycline moities are linked through their respective C-14 carbon atoms by a cross-linking substituent, said cross-linking substituent being hydroxy-dicarboxylic acid hydrazones or amino-dicarboxylic acid hydrazones.
Claim 5
Dependent Claim
33 words
As compositions of matter, bis-anthracycline compounds wherein two anthracycline moities are linked through their respective C-14 carbon atoms by a cross-linking substituent, said cross-linking substituent being hydroxy-dicarboxylic acid hydrazones or amino-dicarboxylic acid hydrazones.
Claim 6
Dependent Claim
21 words
The compositions of claim 1 or 3 wherein the anthracycline moieties are linked by the substituent ##STR35## wherein n=1 to 6.
Claim 7
Dependent Claim
15 words
The compositions of claim 1 wherein said cross-linking substituent is ##STR36## wherein n=1 to 6.
Claim 8
Dependent Claim
26 words
The compounds: ##STR37## wherein n=1 to 6 and R 1 is H or CH 3 , and R 2 is CH 3 or CH 2 OH.
Claim 9
Dependent Claim
26 words
The compounds: ##STR37## wherein n=1 to 6 and R 1 is H or CH 3 , and R 2 is CH 3 or CH 2 OH.
Claim 10
Dependent Claim
16 words
The bis-anthracyclines of claim 1 wherein said bis-anthracyclines are in the pharmacologically acceptable addition salt form.
Claim 11
Dependent Claim
26 words
The compounds: ##STR38## wherein n=1 to 4 and R 1 is H or CH 3 , and R 2 is CH 3 or CH 2 OH.
Claim 12
Dependent Claim
26 words
The compounds: ##STR38## wherein n=1 to 4 and R 1 is H or CH 3 , and R 2 is CH 3 or CH 2 OH.
Claim 13
Dependent Claim
34 words
The bis-anthracycline compound: ##STR39## wherein R 1 is H or CH 3 ; R 2 is CH 3 or CH 2 OH or; and R 3 is H or OH and n=0 to 3.
Claim 14
Dependent Claim
34 words
The bis-anthracycline compound: ##STR39## wherein R 1 is H or CH 3 ; R 2 is CH 3 or CH 2 OH or; and R 3 is H or OH and n=0 to 3.
Claim 15
Dependent Claim
13 words
The bis-anthracyclines of claim 1 in the alpha-, beta-, or alpha-beta, isomeric forms.
Claim 16
Independent Claim
58 words
A method of producing bis-anthracycline compounds comprising reacting anthracyclines in a solvent medium with a cross-linking agent in the presence of an acid at slightly elevated temperatures, said cross-linking agent being hydroxy-dicarboxylic acid dihydrizades or amino-dicarboxylic acid dihydrizides, for a period of time sufficient to produce the bis-anthracycline compounds, and recovering the bis-anthracycline compounds from the reactant solution.
Claim 17
Independent Claim
58 words
A method of producing bis-anthracycline compounds comprising reacting anthracyclines in a solvent medium with a cross-linking agent in the presence of an acid at slightly elevated temperatures, said cross-linking agent being hydroxy-dicarboxylic acid dihydrizades or amino-dicarboxylic acid dihydrizides, for a period of time sufficient to produce the bis-anthracycline compounds, and recovering the bis-anthracycline compounds from the reactant solution.
Claim 18
Dependent Claim
19 words
The method of claim 11 wherein the cross-linking agent is a reaction product of a hydroxy-dicarboxylic acid and hydrazine.
Claim 19
Dependent Claim
19 words
The method of claim 11 wherein the cross-linking agent is a reaction product of an amino-dicarboxylic acid and hydrazine.
Claim 20
Dependent Claim
18 words
The method as in claim 11 wherein the cross-linking agent is a reaction product of amino-diesters and hydrazine.
Claim 21
Dependent Claim
17 words
The method of claim 11 wherein the reaction takes place at a temperature of about 25° C.
Claim 22
Dependent Claim
16 words
The method of claim 11 wherein a strong organic acid is added to the reaction medium.
Claim 23
Dependent Claim
12 words
The method of claim 16 wherein the organic acid is acetic acid.
Claim 24
Dependent Claim
15 words
The method of claim 11 wherein a mineral acid is added to the reaction medium.
Claim 25
Dependent Claim
16 words
The method of claim 11 wherein a strong organic base is added to the reaction medium.
Claim 26
Dependent Claim
11 words
The method of claim 19 wherein the organic base is pyridine.
Claim 27
Dependent Claim
15 words
The method of claim 11 wherein an inorganic base is added to the reaction medium.
Claim 28
Dependent Claim
16 words
The bis-anthracycline compounds of claim 1, 2, 3, 6, 7, 8 or 9 incorporated into liposomes.
References Cited (Backward Citations)
US4112217A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-04-20 | 1984-10-20 | 1985-04-21 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-04-20 | 1988-10-20 | 1989-04-21 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-04-20 | 1992-10-20 | 1993-04-21 | $7700.00 | Window Closed / Lapsed |