US5436243A
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Aminoanthraquinone derivatives to combat multidrug resistance
Assignee: PHARMACEUTICALS Corp
•
Filing: 1993-11-17
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Granted: 1995-07-25
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Expires: 2013-11-17
Abstract
Abstract Potentiating agents inhibit the development of multidrug resistance, reduce drug-resistance in drug-resistant tumors, or sensitize tumors to antineoplastic drugs, thereby potentiating the effect of antineoplastic agents. The potentiating agents are aminoanthraquinones, preferably 1,4-bis(N-substituted) amino anthraquinones, and pharmaceutically acceptable salts thereof.
Inventors
- 👤 Clifford W. Sachs
- 👤 Robert L. Fine
- 👤 Lawrence M Ballas
- 👤 R. Ivy Carroll
- 👤 Robert Bell
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:07
CPC Classifications
A; A61; A61K; A61K31/00; A61K31/70; A61K31/33; A61K31/395; A61K31/435; A61K31/44; A61K31/445; A61K31/47; A61K31/475; A61K31/495; A61K31/535; A61K45/00; A61K45/06
Claims Analysis
Total Claims: 26
Claim 1
Independent Claim
135 words
A method of reducing drug-resistance in a subject having a drug-resistant cancer, said method comprising: administering to the subject a drug-resistance reducing amount of a potentiating agent, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR11## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group of moieties consisting of: ##STR12##
Claim 2
Independent Claim
135 words
A method of reducing drug-resistance in a subject having a drug-resistant cancer, said method comprising: administering to the subject a drug-resistance reducing amount of a potentiating agent, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR11## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group of moieties consisting of: ##STR12##
Claim 3
Dependent Claim
40 words
The method of claim 1, wherein the potentiating agents are compounds according to Formula I, or a pharmaceutically acceptable salt thereof, or combinations thereof, and wherein R 1 , R 2 , R 3 , and R 4 are H.
Claim 4
Dependent Claim
98 words
A pharmaceutical composition for the potentiation of the effect of anticancer drugs, said composition comprising a potentiating agent together with a pharmaceutically acceptable carrier or diluent, and an antineoplastic drug, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), or a pharmaceutically acceptable salt thereof or combinations thereof, wherein ##STR13## wherein: R 1 , R 2 , R 3 , and R 4 are H; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR14##
Claim 5
Dependent Claim
98 words
A pharmaceutical composition for the potentiation of the effect of anticancer drugs, said composition comprising a potentiating agent together with a pharmaceutically acceptable carrier or diluent, and an antineoplastic drug, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), or a pharmaceutically acceptable salt thereof or combinations thereof, wherein ##STR13## wherein: R 1 , R 2 , R 3 , and R 4 are H; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR14##
Claim 6
Independent Claim
145 words
A method for sensitizing multidrug resistant tumor cells to an antineoplastic drug, said method comprising: administering to multidrug resistant tumor cells an effective sensitizing amount of a potentiating agent and an effective anti-tumor amount of an antineoplastic drug, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I) , a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR15## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR16##
Claim 7
Independent Claim
145 words
A method for sensitizing multidrug resistant tumor cells to an antineoplastic drug, said method comprising: administering to multidrug resistant tumor cells an effective sensitizing amount of a potentiating agent and an effective anti-tumor amount of an antineoplastic drug, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I) , a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR15## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR16##
Claim 8
Dependent Claim
31 words
The method of claim 4, wherein the antineoplastic drug is selected from the group consisting of Vinca alkaloids, anthracyclines, antibiotics, epipodophlotoxins, topoisomerase I and II inhibitors, taxol, taxotere, and taxol derivatives.
Claim 9
Dependent Claim
15 words
The method of claim 4, wherein M is selected from the group consisting of: ##STR17##
Claim 10
Dependent Claim
39 words
The method of claim 6, wherein the potentiating agents are compounds according to Formula I or a pharmaceutically acceptable salt thereof or combinations thereof, wherein R 1 , R 2 , R 3 , and R 4 are H.
Claim 11
Dependent Claim
141 words
A pharmaceutical formulation comprising an effective antitumor amount of an antineoplastic agent and an effective sensitizing amount of a potentiating agent, wherein said potentiating agent sensitizes multidrug resistant tumor cells to said antitumor agent and wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR18## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR19##
Claim 12
Dependent Claim
141 words
A pharmaceutical formulation comprising an effective antitumor amount of an antineoplastic agent and an effective sensitizing amount of a potentiating agent, wherein said potentiating agent sensitizes multidrug resistant tumor cells to said antitumor agent and wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR18## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR19##
Claim 13
Dependent Claim
31 words
The formulation of claim 8, wherein the antineoplastic drug is selected from the group consisting of Vinca alkaloids, anthracyclines, antibiotics, epipodophlotoxins, topoisomerase I and II inhibitors, taxol, taxotere, and taxol derivatives.
Claim 14
Dependent Claim
15 words
The formulation of claim 8, wherein M is selected from the group consisting of: ##STR20##
Claim 15
Dependent Claim
40 words
The formulation of claim 8, wherein the potentiating agents are compounds according to Formula I or a pharmaceutically acceptable salt thereof or combinations thereof, and wherein R 1 , R 2 , R 3 , and R 4 are H.
Claim 16
Independent Claim
146 words
A method of selectively inhibiting the growth of tumor cells in a subject in need of such treatment, said method comprising: administering to said subject an effective amount of an anticancer drug independently or in combination with a potentiating agent, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR21## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR22##
Claim 17
Independent Claim
146 words
A method of selectively inhibiting the growth of tumor cells in a subject in need of such treatment, said method comprising: administering to said subject an effective amount of an anticancer drug independently or in combination with a potentiating agent, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR21## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR22##
Claim 18
Dependent Claim
31 words
The method of claim 12, wherein the antineoplastic drug is selected from the group consisting of Vinca alkaloids, anthracyclines, antibiotics, epipodophlotoxins, topoisomerase I and II inhibitors, taxol, taxotere, and taxol derivatives.
Claim 19
Dependent Claim
27 words
The method of claim 12, wherein the amount of the potentiating agent administered ranges from about 1 to about 400 mg/kg/day in a single or divided dose.
Claim 20
Dependent Claim
15 words
The method of claim 12, wherein M is selected from the group consisting of: ##STR23##
Claim 21
Dependent Claim
40 words
The method of claim 12, wherein the potentiating agents are compounds according to Formula I or a pharmaceutically acceptable salt thereof or combinations thereof, and wherein R 1 , R 2 , R 3 , and R 4 are H.
Claim 22
Independent Claim
141 words
A method for sensitizing tumor cells to an antineoplastic drug, said method comprising: administering to said tumor cells an effective sensitizing amount of a potentiating agent and an effective anti-tumor amount of said antineoplastic drug, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR24## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR25##
Claim 23
Independent Claim
141 words
A method for sensitizing tumor cells to an antineoplastic drug, said method comprising: administering to said tumor cells an effective sensitizing amount of a potentiating agent and an effective anti-tumor amount of said antineoplastic drug, wherein said potentiating agent is a compound selected from the group consisting of a compound of Formula (I), a compound of Formula (II), a pharmaceutically acceptable salt thereof and combinations thereof, wherein ##STR24## wherein: R 1 is H or an alkyl chain with 1-7 carbon atoms; R 2 is H or an alkyl chain with 1-7 carbon atoms; R 3 is H or an alkyl chain with 1-7 carbon atoms; R 4 is H or an alkyl chain with 1-7 carbon atoms; x is an integer ranging from 3 to 12; Y is O or NH; and M is selected from the group consisting of: ##STR25##
Claim 24
Dependent Claim
13 words
The method of claim 17, wherein the antineoplastic drug is a Vinca alkaloid.
Claim 25
Dependent Claim
15 words
The method of claim 17, wherein M is selected from the group consisting of: ##STR26##
Claim 26
Dependent Claim
40 words
The method of claim 19, wherein the potentiating agents are compounds according to Formula I or a pharmaceutically acceptable salt thereof or combinations thereof; and wherein R 1 , R 2 , R 3 , and R 4 are H.
References Cited (Backward Citations)
BE639298A
Cited
DE1794385A1
Cited
US3960751A
Cited
GB2000029A
Cited
DE2835661A1
Cited
US4197249A
Cited
US4310666A
Cited
US4526989A
Cited
US4598155A
Cited
US4540788A
Cited
US4762648A
Cited
US4675283A
Cited
US4732893A
Cited
US4837306A
Cited
US4894451A
Cited
US4782056A
Cited
US4765972A
Cited
US5187266A
Cited
US5091552A
Cited
US5055459A
Cited
US4816450A
Cited
US4897403A
Cited
US4923871A
Cited
US4911924A
Cited
US4904582A
Cited
US4999344A
Cited
US5004758A
Cited
US5130303A
Cited
US5182267A
Cited
US5104858A
Cited
WO1990004177A1
Cited
US5112817A
Cited
US5134168A
Cited
US5114951A
Cited
US4973675A
Cited
US5124330A
Cited
US5124338A
Cited
WO1990015599A1
Cited
US5124339A
Cited
WO1991002084A1
Cited
US4990538A
Cited
US5025020A
Cited
US5005588A
Cited
WO1991006658A2
Cited
US5190957A
Cited
US5182293A
Cited
US5160727A
Cited
US4996321A
Cited
US5021426A
Cited
US5114919A
Cited
WO1992007557A1
Cited
WO1992007558A1
Cited
WO1992011034A1
Cited
WO1992013551A1
Cited
WO1992014467A1
Cited
WO1992018131A1
Cited
WO1992020698A1
Cited
US5173486A
Cited
US5182387A
Cited
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| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
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| 3.5 Years (Year 4) | 1998-07-24 | 1999-01-23 | 1999-07-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 2002-07-24 | 2003-01-23 | 2003-07-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2006-07-24 | 2007-01-23 | 2007-07-25 | $7700.00 | Window Closed / Lapsed |