1,4-bis-(amino-hydroxyalkylamino)-anthraquinones for inhibiting protein kinase C
AssigneeSphinx Pharmaceuticals Corporation
InventorsJack B. Jiang, Mary G. Johnson
Life of this patent
Estimating the term…
Abstract
The present invention provides novel substituted anthraquinones having the formula ##STR1## wherein R.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl; m and n are independently 1, 2, or 3; X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ; R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 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.
Claims39
A substituted anthraquinone having the formula ##STR4## wherein R.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
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.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
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.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl,;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
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.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4 Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
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.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
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.sub.1 and R.sub.2 are independently H, alkyl, aryl, or arylalkyl;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
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.sub.1 and R.sub.2 are independently, H, alkyl, aryl, or arylalkyl;
- m and n are independently 1, 2, or 3;
- X is H, OH, NR.sub.3 R.sub.4, Cl, Br, I, F, alkyl, aryl alkoxy, aroxy, COOR.sub.5, or CONR.sub.6 R.sub.7 ;
- R.sub.3, R.sub.4, R.sub.5, R.sub.6, and R.sub.7 are independently H, lower alkyl or aryl.
Dependencies are inferred from the claim text.