Novel delta dicarbonyl compounds and methods for using the same

Abstract

Amidomethyl esters, carbonylmercaptomethyl esters, keto-containing esters, amidomethyl thioesters, amidomethyl amides, and methylene dithioesters are disclosed. The novel compounds have two carbonyl groups connected by a linking moiety having an oxygen, sulfur or nitrogen attached to a methylene group, to which is further attached a sulfur, nitrogen or CH 2 group. Methods of treating illnesses and conditions, such as cancer, hemological disorders, inherited metabolic disorders and others, using these compounds are also disclosed.

What is claimed is:  
     
         1 . A compound having the formula (1):  
       
         
           
           
               
               
           
         
         wherein X is selected from the group consisting of oxygen, sulfur and N(R);  
         wherein Y is selected from the group consisting of sulfur, N(R), and CH 2 ;  
         wherein R is either H or CH 3 ;  
         wherein R 1  and R 2  are the same or different and have the general formula (2);  
         —(CH 2 ) o —(R 3 ) p —(CH 2 ) q —(R 4 ) r —(CH 2 ) s -Z  (2)  
         wherein R 3  and R 4  are the same or different and are selected from the group (CH═CH), (C≡C), sulfur and oxygen;  
         wherein Z is selected from the group consisting of hydrogen and substituted or unsubstituted aryl, heteroaryl, cycloalkyl having the general formula C n H 2n-1  and alkoxy;  
         wherein n is 3 or greater; and  
         wherein o, p, q, r and s are the same or different and are each between 0 and 10.  
       
     
     
         2 . The compound of  claim 1 , wherein Z is substituted with one or more members of the group consisting of halogen, hydroxy, alkyl, alkoxy, cyano, amino, nitro, carbonyl, and halogenated hydrocarbon groups, and when more than one substituents are present they can be the same or different.  
     
     
         3 . The compound of  claim 1 , wherein X is oxygen and Y is N(CH 3 ).  
     
     
         4 . The compound of  claim 1 , wherein X is oxygen, Y is N(CH 3 ), one of R 1  or R 2  is CH 2 CH 2 CH 3 , and the other of R 1  or R 2  is —CH═CH—C 6 H 5 .  
     
     
         5 . The compound of  claim 1 , wherein X is oxygen, Y is sulfur, one of R 1  or R 2  is CH 2 CH 2 CH 3 , and the other of R 1  or R 2  is —CH═CH—C 6 H 5 .  
     
     
         6 . The compound of  claim 1 , wherein X is oxygen, Y is CH 2 , R 1  is —CH═CH—C 6 H 5 , and R 2  is CH 2 CH 2 CH 3 .  
     
     
         7 . The compound of  claim 1 , wherein X is oxygen, Y is N(CH 3 ), R 1  is CH 2 CH 2 CH 3  and R 2  is CH 2 OCH 2 CH 2 OCH 3 .  
     
     
         8 . The compound of  claim 1 , wherein R 1  and R 2  are the same or different and are selected from the group consisting of CH 2 CH 3 ; CH 2 CH 2 CH 3 ; and CH 2 CH 2 CH 2 CH 3 .  
     
     
         9 . The compound of  claim 1 , wherein both X and Y are sulfur and both R 1  and R 2  are CH 2 CH 2 CH 3 .  
     
     
         10 . The compound of  claim 1 , wherein both X and Y are sulfur and both R 1  and R 2  are CH 2 CH 3 .  
     
     
         11 . A method for treating an illness in a patient comprising administering to said patient an effective amount of a compound having the formula:  
       
         
           
           
               
               
           
         
         wherein X is selected from the group consisting of oxygen, sulfur and N(R);  
         wherein Y is selected from the group consisting of sulfur, N(R), and CH 2 ;  
         wherein R is either H or CH 3 ;  
         wherein R 1  and R 2  are the same or different and having the general formula (2);  
         —(C 2 ) o —(R 3 ) p —(CH 2 ) q —(R 4 ) r —(CH 2 ) s -Z  (2)  
         wherein R 3  and R 4  are the same or different and are selected from the group (CH═CH), (C≡C), sulfur and oxygen;  
         wherein Z is selected from the group consisting of hydrogen and substituted or unsubstituted aryl, heteroaryl, cycloalkyl having the general formula C n H 2n-1  and alkoxy;  
         wherein n is 3 or greater;  
         wherein o, p, q, r and s are the same or different and are each between 0 and 10.  
       
     
     
         12 . The method of  claim 11 , wherein said compound is contained in a pharmaceutically acceptable carrier.  
     
     
         13 . The method of  claim 11 , wherein said illness is cancer, hemological disease or an inherited metabolic disease.  
     
     
         14 . The method of  claim 11 , wherein said treatment results in one or more therapeutic benefits selected from the group consisting of retarding or eliminating tumor growth, inducing apoptosis of tumor cells, healing wounds, healing cutaneous ulcers, ameliorating gastrointestinal disorders, modulating gene expression, inhibiting telomerase activity, inducing tolerance to antigens, preventing or ameliorating protozoan infection, inhibiting histone deacetylace in cells, modulating an immune response, and ameliorating the effects of a cytotoxic agent, stimulating hematopoietic cells ex vivo and protecting against injury to hair follicles.  
     
     
         15 . The method of  claim 11 , wherein said effective amount is at least about 10 milligrams per meter 2  of body mass, per day.  
     
     
         16 . The method of  claim 11 , wherein said compound is administered orally, parenterally, transdermally, transmucosally, intranasally, rectally or topically.  
     
     
         17 . The method of  claim 11 , wherein said effective amount is an amount sufficient to effect a therapeutic benefit.  
     
     
         18 . A pharmaceutical composition comprising an effective amount of a compound of  claim 1  and a pharmaceutically acceptable carrier.