Dicarbonyl derivatives and methods of use

Abstract

Derivatives of dicarbonyl compounds having antitumor and antibiotic activity which can be used as anticancer agents.

1 - 17 . (canceled) 
     
     
         18 . A method for treating a disease or condition in a mammal characterized by undesired cellular proliferation or hyperproliferation comprising identifying the mammal afflicted with said disease or condition and administering to said afflicted mammal a composition comprising the compound or pharmaceutically acceptable salt thereof having the formula (I) 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2 , R 3 , R 4 , R 5 , and R 6  are independently a hydrogen atom or an alkyl, alkenyl, alkynyl, or aryl comprising 1 to 30 carbon atoms and which is unsubstituted or substituted by at least one of hydroxy, cyano, mercapto, halogen, —OR 7 , SR 7 , —NR 7 R 8 , —CONR 7 R 8 , or —OCONR 7 R 8 , wherein 
         R 7  and R 8  are a hydrogen atom; an alkyl, alkenyl, or alkynyl comprising 1 to 20 carbon atoms; a cyclic or heterocyclic group comprising 5 or 6 ring atoms of which from 0 to 3 are nitrogen, oxygen, sulphur or a combination thereof of hetero-atoms, said cyclic or heterocyclic group being unsubstituted or substituted by at least one of hydroxy, cyano, mercapto, halogen, or an alkyl group comprising 1 to 6 carbon atoms; and 
         X and Y are respectively O, NR 7  or S, wherein when X and Y are O, and if R 2 , R 4  are hydrogen, R 1 -R 3  or both R 1 -R 3  and R 5 -R 6  form a cyclic or an acyclic alkenyl; when X and Y are O, and if R 2 , R 4  form a single bond, R 1  is 
       
       
         
           
           
               
               
           
         
         wherein Ar is an aryl or heteroaryl. 
       
     
     
         19 . The method of  claim 18 , comprising administering to said afflicted mammal a composition comprising compound or pharmaceutically acceptable salt thereof having the formula (I) wherein X and Y are O, and R 6  is NR 7 R 8 . 
     
     
         20 . The method of  claim 18 , comprising administering to said afflicted mammal a composition comprising compound or pharmaceutically acceptable salt thereof having the formula (I) wherein, wherein X and Y are O. 
     
     
         21 . The method of  claim 18 , comprising administering to said afflicted mammal a composition comprising compound or pharmaceutically acceptable salt thereof, wherein the compound has the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 21 , wherein in said compound R 7  and R 8  are C 1 -C 10  alkyl and C 6 -C 10  aryl, respectively. 
     
     
         23 . The method of  claim 18 , comprising administering to said afflicted mammal a composition comprising compound or pharmaceutically acceptable salt thereof, wherein the compound has the following formula: 
       
         
           
           
               
               
           
         
       
     
     
         24 . The method of  claim 23 , wherein in said compound R 7  and R 8  are C 1 -C 10  alkyl and C 6 -C 10  aryl, respectively. 
     
     
         25 . The method of  claim 24 , wherein in said compound X is H, 3-OMe, 4-OMe, or 3,4-di-OMe. 
     
     
         26 . The method of  claim 18 , wherein said disease or condition is cancer. 
     
     
         27 . The method of  claim 18 , wherein said composition is administered as a single intravenous dose, a single intraperitoneal dose, a slow long-term infusion, multiple short-term daily infusions, and combinations thereof. 
     
     
         28 . The method of  claim 18 , wherein said cancer is selected from the group consisting of cancers of the liver and biliary tree, intestinal cancers, colorectal cancer, ovarian cancer, small cell and non-small cell lung cancer, breast cancer, sarcomas, fibrosarcoma, malignant fibrous histiocytoma, embryonal rhabdomysocarcoma, leiomysosarcoma, neuro-fibrosarcoma, osteosarcoma, synovial sarcoma, liposarcoma, alveolar soft part sarcoma, neoplasms of the central nervous systems, brain cancer, and lymphomas, including Hodgkin's lymphoma, lymphoplasmacytoid lymphoma, follicular lymphoma, mucosa-associated lymphoid tissue lymphoma, mantle cell lymphoma, B-lineage large cell lymphoma, Burkitt's lymphoma, and T-cell anaplastic large cell lymphoma, and combinations thereof. 
     
     
         29 . The method of  claim 27 , further comprising administering to said afflicted mammal a said second active agent selected from the group consisting of taxane, doxorubicin, 5-FU and other anticancer drugs.