US5141957A
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US
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1,4-bis-(amino-hydroxyalkylamino)-anthraquinones for inhibiting protein kinase c
Assignee: Eli Lilly and Co
•
Filing: 1990-11-05
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Granted: 1992-08-25
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Expires: 2010-11-05
Abstract
Abstract The present invention provides novel substituted anthraquinones having the formula <IMAGE> wherein R1 and R2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR3R4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR5, or CONR6R7; R3, R4, R5, R6, and R7 are independently H, lower alkyl or aryl useful for inhibiting protein kinase C and treating conditions related to, or affected by inhibition of protein kinase C, particularly cancer tumors, inflammatory disease, reperfusion injury, and cardiac dysfunctions related to reperfusion injury.
Inventors
- 👤 Jack B. Jiang
- 👤 Mary G. Johnson
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-06 04:16
CPC Classifications
C; C07; C07C; C07C225/00; C07C225/24; C07C225/26; C07C225/32; C07C225/34; C07C225/36; A; A61; A61P; A61P29/00; A61P35/00; A61P43/00; A61P7/00; A61P7/02; A61P9/00
Claims Analysis
Total Claims: 46
Claim 1
Independent Claim
77 words
A substituted anthraquinone having the formula ##STR4## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 2
Dependent Claim
77 words
A substituted anthraquinone having the formula ##STR4## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 3
Dependent Claim
38 words
The substituted anthraquinone of claim 1 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 4
Dependent Claim
28 words
The substituted anthraquinone of claim 2 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 5
Dependent Claim
22 words
A pharmaceutical composition for inhibiting protein kinase C comprising a substituted anthraquinone of claim 1 and a pharmaceutically acceptable carrier or diluent.
Claim 6
Dependent Claim
22 words
A pharmaceutical composition for inhibiting protein kinase C comprising a substituted anthraquinone of claim 2 and a pharmaceutically acceptable carrier or diluent.
Claim 7
Dependent Claim
22 words
A pharmaceutical composition for inhibiting protein kinase C comprising a substituted anthraquinone of claim 3 and a pharmaceutically acceptable carrier or diluent.
Claim 8
Independent Claim
95 words
A method of inhibiting protein kinase C which comprises contacting protein kinase C with an inhibitory amount of a substituted anthraquinone having the formula ##STR5## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 9
Independent Claim
95 words
A method of inhibiting protein kinase C which comprises contacting protein kinase C with an inhibitory amount of a substituted anthraquinone having the formula ##STR5## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 10
Dependent Claim
37 words
The method of claim 7 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 11
Dependent Claim
27 words
The method of claim 8 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 12
Independent Claim
99 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR6## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl,; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 13
Independent Claim
99 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR6## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl,; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 14
Dependent Claim
37 words
The method of claim 10 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 15
Dependent Claim
27 words
The method of claim 11 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 16
Dependent Claim
29 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with an amount of a compound of claim 1 effective to inhibit said oxidative burst.
Claim 17
Dependent Claim
29 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with an amount of a compound of claim 2 effective to inhibit said oxidative burst.
Claim 18
Dependent Claim
29 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with an amount of a compound of claim 3 effective to inhibit said oxidative burst.
Claim 19
Independent Claim
97 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR7## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 20
Independent Claim
97 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR7## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 21
Dependent Claim
37 words
The method of claim 16 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 22
Dependent Claim
27 words
The method of claim 17 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 23
Dependent Claim
26 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation an amount of a compound of claim 1 effective to inhibit inflammation.
Claim 24
Dependent Claim
26 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation an amount of a compound of claim 2 effective to inhibit inflammation.
Claim 25
Dependent Claim
26 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation an amount of a compound of claim 3 effective to inhibit inflammation.
Claim 26
Independent Claim
101 words
A method for inhibiting growth of mammalian tumor cells which comprises contacting a mammalian tumor cell with a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR8## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 27
Independent Claim
101 words
A method for inhibiting growth of mammalian tumor cells which comprises contacting a mammalian tumor cell with a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR8## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 28
Dependent Claim
37 words
The method of claim 22 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 29
Dependent Claim
27 words
The method of claim 23 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 30
Dependent Claim
34 words
A method for inhibiting growth of mammalian tumor cells which comprises contacting a mammalian tumor cell with an amount of a compound of claim 1 effective to inhibit growth of said mammalian tumor cell.
Claim 31
Dependent Claim
34 words
A method for inhibiting growth of mammalian tumor cells which comprises contacting a mammalian tumor cell with an amount of a compound of claim 2 effective to inhibit growth of said mammalian tumor cell.
Claim 32
Dependent Claim
34 words
A method for inhibiting growth of mammalian tumor cells which comprises contacting a mammalian tumor cell with an amount of a compound of claim 3 effective to inhibit growth of said mammalian tumor cell.
Claim 33
Independent Claim
99 words
A method for treating mammalian tumors which comprises administering to a mammal having a tumor a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR9## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 34
Independent Claim
99 words
A method for treating mammalian tumors which comprises administering to a mammal having a tumor a protein kinase C inhibitory concentration of a substituted anthraquinone having the formula ##STR9## wherein R 1 and R 2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 35
Dependent Claim
37 words
The method of claim 28 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 36
Dependent Claim
27 words
The method of claim 29 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 37
Dependent Claim
30 words
A method for treating mammalian tumors which comprises administering to a mammal having a tumor an amount of a compound of claim 1 effective to inhibit growth of said tumor.
Claim 38
Dependent Claim
30 words
A method for treating mammalian tumors which comprises administering to a mammal having a tumor an amount of a compound of claim 2 effective to inhibit growth of said tumor.
Claim 39
Dependent Claim
30 words
A method for treating mammalian tumors which comprises administering to a mammal having a tumor an amount of a compound of claim 3 effective to inhibit growth of said tumor.
Claim 40
Independent Claim
94 words
A method of inhibiting keratinocyte proliferation comprising administering to a keratinocyte a protein kinase C inhibitory amount of a compound having the formula ##STR10## wherein R 1 and R 2 are independently, H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 41
Independent Claim
94 words
A method of inhibiting keratinocyte proliferation comprising administering to a keratinocyte a protein kinase C inhibitory amount of a compound having the formula ##STR10## wherein R 1 and R 2 are independently, H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR 3 R 4 , Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR 5 , or CONR 6 R 7 ; R 3 , R 4 , R 5 , R 6 , and R 7 are independently H, lower alkyl or aryl.
Claim 42
Dependent Claim
37 words
The method of claim 33 wherein R 1 and R 2 independently are H, lower alkyl, or arylalkyl; m and n are independently 1 or 2; and X is H, OH, Cl, Br, I, F, or alkoxy.
Claim 43
Dependent Claim
27 words
The method of claim 35 wherein R 1 and R 2 independently are H or arylalkyl; m and n are 1; and X is H or OH.
Claim 44
Dependent Claim
28 words
A method of inhibiting mammalian keratinocyte cell proliferation comprising administering to said keratinocyte an amount of a compound of claim 1 effective to inhibit proliferation of said keratinocyte.
Claim 45
Dependent Claim
28 words
A method of inhibiting mammalian keratinocyte cell proliferation comprising administering to said keratinocyte an amount of a compound of claim 2 effective to inhibit proliferation of said keratinocyte.
Claim 46
Dependent Claim
28 words
A method of inhibiting mammalian keratinocyte cell proliferation comprising administering to said keratinocyte an amount of a compound of claim 3 effective to inhibit proliferation of said keratinocyte.
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USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1995-08-25 | 1996-02-24 | 1996-08-25 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1999-08-25 | 2000-02-24 | 2000-08-25 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 2003-08-25 | 2004-02-24 | 2004-08-25 | $7700.00 | Window Closed / Lapsed |