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US5344841A
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Bis-(hydroxylakylamino)-anthraquinone inhibitors of protein kinase C
Assignee: Eli Lilly and Co
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Filing: 1991-10-30
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Granted: 1994-09-06
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Expires: 2011-10-30
Abstract
Abstract PCT No. PCT/US91/08026 Sec. 371 Date Jun. 8, 1992 Sec. 102(e) Date Jun. 8, 1992 PCT Filed Oct. 30, 1991 PCT Pub. No. WO92/07557 PCT Pub. Date May 14, 1992. <IMAGE> ( alpha ) The present invention provides novel substituted anthraquinones having formula ( alpha ), wherein R1 and R2 are independently H, C1-C10 alkyl, aryl, arylalkyl, alkylaryl, or R1 and R2 taken together with the adjacent nitrogen atom N form a substituted or unsubstituted cyclic ring which may contain additional heteroatoms; n and m are independently 1, 2, or 3; A is halogen, OH, alkoxy, OCO(NR3R4), S-C(NH2)=NR5, or when m=1, comprises an oxirane ring with the adjacent oxygen atom; R3, R4, and R5 are independently H, alkyl, or aryl; X is H, OH, NR6R7, Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR8, or CONR9R10; and R6, R7, R8, R9, and R10 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
2026-10-24 22:51
CPC Classifications
C; C07; C07D; C07D303/00; C07D303/02; C07D303/36; A; A61; A61P; A61P35/00; A61P43/00; C07C; C07C225/00; C07C225/24; C07C225/26; C07C225/32; C07C225/34; C07C225/36; C07C229/00; C07C229/52; C07C229/68; C07C229/72; C07C229/74; C07C271/00; C07C271/06; C07C271/08; C07C271/10; C07C271/12; C07C335/00; C07C335/30; C07C335/32; C07C2603/00; C07C2603/02; C07C2603/04; C07C2603/22; C07C2603/24
Claims Analysis
Total Claims: 25
Claim 1
Independent Claim
152 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 ##STR4## wherein R 1 and R 2 are independently H, C 1 -C 10 alkyl, aryl, arylalkyl, or alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 9 R 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl.
Claim 2
Independent Claim
152 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 ##STR4## wherein R 1 and R 2 are independently H, C 1 -C 10 alkyl, aryl, arylalkyl, or alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 9 R 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl.
Claim 3
Dependent Claim
70 words
The method of claim 1 wherein R 1 and R 2 independently are H or lower alkyl; n and m are independently 1 or 2; A is halogen, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or when m=1 , comprises said oxirane; R 3 , R 4 , and R 5 are independently H or alkyl; and X is H, HO, Cl, Br, I, F, or alkoxy.
Claim 4
Dependent Claim
56 words
The method of claim 2 wherein R 1 and R 2 independently are lower alkyl; m and n are 1; A is Cl, Br, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or comprises said oxirane ring; R 3 , R 4 , and R 5 are H; and X is H or OH.
Claim 5
Independent Claim
157 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with a substituted anthraquinone having the formula ##STR5## wherein R 1 and R 2 are independently H, C 1-C 10 alkyl, aryl, arylalkyl, or alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 9 R 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl in an amount effective to inhibit said oxidative burst.
Claim 6
Independent Claim
157 words
A method of inhibiting an oxidative burst in neutrophils which comprises contacting a neutrophil with a substituted anthraquinone having the formula ##STR5## wherein R 1 and R 2 are independently H, C 1-C 10 alkyl, aryl, arylalkyl, or alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 9 R 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl in an amount effective to inhibit said oxidative burst.
Claim 7
Dependent Claim
70 words
The method of claim 4 wherein R 1 and R 2 independently are H or lower alkyl; n and m are independently 1 or 2; A is halogen, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or when m=1, comprises said oxirane ring; R 3 , R 4 , and R 5 are independently H or alkyl; and X is H, HO, Cl, Br, I, F, or alkoxy.
Claim 8
Dependent Claim
56 words
The method of claim 5 wherein R 1 and R 2 independently are lower alkyl; m and n are 1; A is Cl, Br, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or comprises said oxirane ring; R 3 , R 4 , and R 5 are H; and X is H or OH.
Claim 9
Dependent Claim
15 words
The method of claim 4 wherein said amount is a protein kinase C inhibitory amount.
Claim 10
Dependent Claim
15 words
The method of claim 5 wherein said amount is a protein kinase C inhibitory amount.
Claim 11
Dependent Claim
15 words
The method of claim 6 wherein said amount is a protein kinase C inhibitory amount.
Claim 12
Independent Claim
153 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation a substituted anthraquinone having the formula ##STR6## wherein R 1 and R 2 are independently H, C 1 -C 10 alkyl, aryl, arylalkyl, or alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl in an amount effective to inhibit inflammation.
Claim 13
Independent Claim
153 words
A method for treating inflammation which comprises administering to a mammal suffering from inflammation a substituted anthraquinone having the formula ##STR6## wherein R 1 and R 2 are independently H, C 1 -C 10 alkyl, aryl, arylalkyl, or alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl in an amount effective to inhibit inflammation.
Claim 14
Dependent Claim
69 words
The method of claim 10 wherein R 1 and R 2 independently are H or lower alkyl; n and m are independently 1 or 2; A is halogen, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or when m=1, comprises said oxirane ring; R.sub. 3, R 4 , and R 5 are independently H or alkyl; and X is H, HO, Cl, Br, I, F, or alkoxy.
Claim 15
Dependent Claim
56 words
The method of claim 11 wherein R 1 and R 2 independently are lower alkyl; m and n are 1; A is Cl, Br, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or comprises said oxirane ring; R 3 , R 4 , and R 5 are H; and X is H or OH.
Claim 16
Dependent Claim
15 words
The method of claim 10 wherein said amount is a protein kinase C inhibitory amount.
Claim 17
Dependent Claim
15 words
The method of claim 11 wherein said amount is a protein kinase C inhibitory amount.
Claim 18
Dependent Claim
15 words
The method of claim 12 wherein said amount is a protein kinase C inhibitory amount.
Claim 19
Independent Claim
153 words
A method of inhibiting keratinocyte proliferation comprising administering to a keratinocyte a compound having the formula ##STR7## wherein R 1 and R 2 are independently H, C 1 -C 10 alkyl, aryl, arylalkyl, alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 9 R 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl in an amount effective to inhibit proliferation of said keratinocyte.
Claim 20
Independent Claim
153 words
A method of inhibiting keratinocyte proliferation comprising administering to a keratinocyte a compound having the formula ##STR7## wherein R 1 and R 2 are independently H, C 1 -C 10 alkyl, aryl, arylalkyl, alkylaryl; n and m are independently 1, 2, or 3; A is Halogen, OH, alkoxy, OCO(NR 3 R 4 ), S--C(NH 2 )═NR 5 , or when m=1, A represents the attachment of the oxygen atom from the adjacent hydroxyl group to form an oxirane ring; R 3 , R 4 , and R 5 are independently H, alkyl, or aryl; X is H, OH, NR 6 R 7 , Cl, Br, I, F, alkyl, aryl, alkoxy, aryloxy, COOR 8 , or CONR 9 R 10 ; and R 6 , R 7 , R 8 , R 9 , and R 10 are independently H, lower alkyl, or aryl in an amount effective to inhibit proliferation of said keratinocyte.
Claim 21
Dependent Claim
70 words
The method of claim 16 wherein R 1 and R 2 independently are H or lower alkyl; n and m are independently 1 or 2; A is halogen, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or when m=1, comprises said oxirane ring; R 3 , R 4 , and R 5 are independently H or alkyl; and X is H, HO, Cl, Br, I, F, or alkoxy.
Claim 22
Dependent Claim
56 words
The method of claim 17 wherein R 1 and R 2 independently are lower alkyl; m and n are 1; A is Cl, Br, OCO(NR 3 R 4 ), SC(NH 2 )═NR 5 , or comprises said oxirane ring; R 3 , R 4 , and R 5 are H; and X is H or OH.
Claim 23
Dependent Claim
15 words
The method of claim 11 wherein said amount is a protein kinase C inhibitory amount.
Claim 24
Dependent Claim
15 words
The method of claim 17 wherein said amount is a protein kinase C inhibitory amount.
Claim 25
Dependent Claim
15 words
The method of claim 18 wherein said amount is a protein kinase C inhibitory amount.
References Cited (Backward Citations)
US1540733A
Cited
US2411148A
Cited
US3960751A
Cited
US4197249A
Cited
US4310666A
Cited
US4526989A
Cited
US4598155A
Cited
US4540788A
Cited
US4762648A
Cited
US4894451A
Cited
JPS6315853A
Cited
US4816450A
Cited
JPH0219819A
Cited
DE3827974A1
Cited
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