Benzimidazole vascular damaging agents
AssigneeAngiogene Pharmaceuticals Ltd.
InventorPeter David Davis
Life of this patent
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Abstract
Vascular damaging agents composed of substituted 5(6)-substituted benzimidazole-2-carbamates are provided. These agents are useful in the preparation of medicaments for the treatment of diseases involving neovascularisation, particularly for the treatment of solid tumors, macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis, and atherosclerosis. Embodiments include a 5(6)-substituted benzimidazole-2-carbamate of formula I wherein A represents a multi-substituted alkyl group or aromatic ring.
Claims6
A composition for treatment of diseases involving angiogenesis comprising at least one 5(6)-substituted benzimidazole-2-carbamate of formula I in an amount sufficient to damage new vasculature:
- wherein:
- alk is an alkyl group;
- X is oxygen, sulfur, sulphinyl, sulphonyl, carbonyl (CO), thiocarbonyl (CS), sulphonyloxy, NH, iminomethylene (C═NH), N-hydroxyiminomethylene, N-alkoxyiminomethylene, dialkoxymethylene, 1,3-dioxolan-2yl, 1,1-ethenyl, a group CHR3 or a bond;
- R1 is hydrogen, alkylaminocarbonyl oralkoxycarbonyl;
- R2 is hydrogen, alkoxycarbonyl, cyanomethyl, cyanoethyl, alkoxymethyl or acetoxymethyl;
- R3 is hydrogen, hydroxy, alkoxy or amino;
- A is a substituted aromatic ring or substituted alkyl group in which at least one substituent is Y selected from phosphate, alkylphosphate, NHCOR4 and NR5COR4 where R4 and R5, which may be the same or different, are each an alkyl group substituted with one or more substituents selected from hydroxy, amino, alkylamino, guanidino, carboxyl, SO3H, sulfate and phosphate;
- and
- prodrugs and pharmaceutically acceptable salts, solvates and hydrates thereof.
A composition for treatment of diseases involving angiogenesis comprising at least one 5(6)-substituted benzimidazole-2-carbamate of formula II in an amount sufficient to damage new vasculature:
- wherein:
- alk is an alkyl group;
- B is an aromatic ring;
- X is oxygen, sulfur, sulphinyl, sulphonyl, carbonyl (CO), thiocarbonyl (CS), sulphonyloxy, NH, iminomethylene (C═NH), N-hydroxyiminomethylene, N-alkoxyiminomethylene, dialkoxymethylene, 1,3-dioxolan-2yl, 1,1-ethenyl, a group CHR3 or a bond;
- R1 is hydrogen, alkylaminocarbonyl or alkoxycarbonyl;
- R2 is hydrogen, alkoxycarbonyl, cyanomethyl, cyanoethyl, alkoxymethyl or acetoxymethyl;
- R3 is hydrogen, hydroxy, alkoxy or amino;
- Y is selected from phosphate, alkylphosphate, NHCOR4 and NR5COR4 where R4 and R5, which may be the same or different, are each an alkyl group substituted with at least one substituent selected from the group consisting of hydroxy, amino, alkylamino, guanidino, carboxyl, SO3H, sulfate and phosphate;
- R7 and R8 are each independently H, alkyl, halogen, hydroxy, amino, alkylamino, dialkylamino, alkoxy, alkylthio, cyano, nitro, or trifluoromethyl;
- and
- prodrugs and pharmaceutically acceptable salts, solvates and hydrates thereof.
Dependencies are inferred from the claim text.