Therapeutic curcumin derivatives

Abstract

Curcumin analogues and methods are provided for treatment of disease.

1 . A method of treating a subject afflicted with Alzheimer's disease or type 2 diabetes, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a curcumin derivative selected from the group consisting of:
 (a) Ar 1 -L-Ar 2  (Formula I); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; and Ar 1  and Ar 2  are each independently aryl groups; and   (b) Ar 1 -L-R 11  (Formula IV); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; Ar 1  is an aryl group; and R 11  is an alkyl group, a heterocyclic group, or a hydrogen.   
     
     
         2 .- 21 . (canceled) 
     
     
         22 . A method of treating a subject afflicted with cancer or a precancerous condition, the method comprising administering to the subject a therapeutically effective amount of a composition comprising a curcumin derivative selected from the group consisting of:
 (a) Ar 1 -L-Ar 2  (Formula I); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; and Ar 1  and Ar 2  are each independently aryl groups; and   (b) Ar 1 -L-R 11  (Formula IV); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; Ar 1  is an aryl group; and R 11  is an alkyl group, a heterocyclic group, or a hydrogen.   
     
     
         23 .- 28 . (canceled) 
     
     
         29 . A compound according to the chemical structure:
 (a) Ar 1 -L-Ar 2  (Formula I); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; and Ar 1  and Ar 2  are each independently aryl groups; or   (b) Ar 1 -L-R 11  (Formula IV); wherein L is a divalent linking group comprising an alkylene or an alkenylene comprising 3, 4, 5, 6, or 7 backbone carbon atoms, wherein one or more of the backbone carbon atoms form part of a carbonyl or secondary alcohol; Ar 1  is an aryl group; and R 11  is an alkyl group, a heterocyclic group, or a hydrogen, or a pharmaceutically acceptable salt thereof.   
     
     
         30 . The compound of  claim 29 , wherein either or both of Ar 1  and Ar 2  is independently a heteroaryl group. 
     
     
         31 . The compound of  claim 29 , wherein the divalent linking group L is unsaturated. 
     
     
         32 . The compound of  claim 29 , wherein L is an alkylene or an alkenylene selected from the group consisting of:
   —CH═CH—CHO—,
     —CH═CH—(CO)—CH═CH—,
     —CH 2 —CH 2 —(CO)—CH 2 —CH 2 —,
     —CH 2 —CH 2 —CH(OH)—CH 2 —CH 2 —,
                       —CH═CH—(CO)—CR═C(OH)—CH═CH—,
     —CH═CH—(CO)—CR 2 —(CO)—CH═CH—, and
     —CH═CH—(CO)—CH—C(OH)—CH═CH—;
   wherein R consists of an alkyl or aryl group comprising 10 carbon atoms or less.   
     
     
         33 . The compound of  claim 29 , wherein at Ar 1  is a phenyl group according to Formula II: 
       
         
           
           
               
               
           
         
         and each of R 1 -R 5  is independently selected from the group consisting of hydroxyl, methyl, methoxyl, dimethylamine, trifluoromethyl, chloro, fluoro, acetoxyl, cyano, and carboxymethyl. 
       
     
     
         34 . The compound of  claim 33 , wherein Ar 2  is a phenyl group according to Formula III: 
       
         
           
           
               
               
           
         
         and each of R 6 -R 10  is independently selected from the group consisting of hydroxyl, methyl; methoxyl, dimethylamine, trifluoromethyl, chloro, fluoro, acetoxyl, cyano, and carboxymethyl.