Compositions and methods to treat diseases characterized by cellular proliferation and angiogenesis

Abstract

Described herein are compositions and methods for preventing and/or treating diseases involving aberrant angiogenesis employing one or more benzo[c]chromen-6-one derivatives.

What is claimed is: 
     
       1. A composition comprising a compound according to Formula I: 
       
         
           
           
               
               
           
         
         wherein, 
         R1 is H or alkyl; 
         R2 is H, OH, O-alkyl, amino, O-heterocyc, O-aryl, O—Ac, O—PO3, O—SO3, OSO2NH2 or O-substituted alkyl wherein said substitution is halo, aryl, or heteroaryl; 
         R3 is OH, O—CH2Aryl, O—CH2heteroaryl, or O-alkylaryl, or O-acyl; 
         R4 is H, Alkyl, CH2Aryl, substituted alkyl, OH, O-alkyl, O-aryl, OCH2Aryl, OCH2Heteroaryl, O-Acyl, OPO3, OSO3, or OSO2NH2; 
         R5 is H, Oxo, aryl, hydroxyl, alkyl, or O-alkyl; 
         R6 is H; 
         R7 is H, Acyl, alkyl, O-alkyl, substituted alkyl wherein said substitution is hydroxyl or sulfamoyl, or O-substituted alkyl wherein said substitution is O—PO3 or OSO3; 
         R8 is H; and 
         X is O, N, or S; and wherein if R3 is OH or O-acyl then R7 is Acyl, alkyl, or substituted alkyl wherein said substitution is hydroxyl; 
         and wherein said compound according to Formula I is selected from the group consisting of 
       
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       . 
     
     
       2. The composition of  claim 1 , wherein said compound comprises 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       3. The composition of  claim 1 , wherein said composition is formulated in a biodegradable or non-biodegradable format for sustained release. 
     
     
       4. A method of treating cancer comprising administering an effective amount to a subject a composition of  claim 1 , wherein said cancer is selected from the group consisting of fibrosarcoma, myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma, endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumor, leiomyosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma, basal cell carcinoma, adenocarcinoma, sweat gland carcinoma, sebaceous gland carcinoma, papillary carcinoma, papillary adenocarcinomas, cystadenocarcinoma, hemangioma, medullary carcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinomas, seminoma, embryonal carcinoma, Wilms' tumor, cervical cancer, testicular tumor, lung carcinoma, small cell lung carcinoma, bladder carcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma, hemangioblastoma, acoustic neuroma, oligodendroglioma, osteosarcoma, meningioma, melanoma, neuroblastoma, retinoblastoma, acousticneuroma, neurofibromas, trachoma and pyogenic granulomas, acute lymphocytic leukemia and acute myelocytic leukemia, chronic leukemia, polycythemia vera, lymphoma, multiple myeloma, Waldenstrom's macroblobulinemia macroglobulinemia, and heavy chain disease. 
     
     
       5. The method of  claim 4  further comprising the co-administration to said subject said one or more compositions of Formula I and a therapeutic agent directed toward the treatment of said disease. 
     
     
       6. The method of  claim 5 , wherein said therapeutic agent is selected from the group consisting of an oncolytic agent, an anti-cancer agent, an anti-nausea agent and an anti-emesis agent. 
     
     
       7. The method of  claim 4 , wherein said administration includes topical, oral, nasal, rectal, and parenteral administration of said one or more compositions. 
     
     
       8. The method of  claim 4 , wherein said one or more compositions is coated on an implant. 
     
     
       9. The method of  claim 8 , wherein said device is a vascular stent. 
     
     
       10. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       11. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       12. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       13. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       14. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       15. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       16. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       17. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       18. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       19. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       20. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       21. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       22. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       23. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       24. The composition of claim 1, wherein said compound according to Formula I is: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       25. The composition of claim 1, wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       26. The composition of claim 10, wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       27. The composition of claim 13, wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       28. The composition of claim 16, wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       29. The composition of claim 23, wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent, or excipient. 
     
     
       30. The composition of claim 24, wherein said composition is a pharmaceutical composition further comprising a pharmaceutically acceptable carrier, diluent, or excipient.