US2016166550A1PendingUtilityA1

Combination Therapies for the Treatment of Alzheimer's Disease and Related Disorders

Assignee: GEN HOSPITAL CORPPriority: Oct 25, 2012Filed: Feb 19, 2016Published: Jun 16, 2016
Est. expiryOct 25, 2032(~6.3 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 25/28A61P 29/00A61P 25/00A61P 17/02A61K 31/047C07K 16/18A61K 31/075A61K 48/00A61K 31/706A61K 39/0005A61K 45/06A61K 31/225A61K 38/185A61K 31/5415A61K 31/438A61K 31/13A61K 31/428A61K 31/55A61K 51/0453A61K 31/713A61K 31/435A61K 31/353A61K 31/194A61K 31/352A61K 31/192
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Claims

Abstract

The present invention relates to combination therapies for treating Alzheimer's disease or an amyloidosis-associated pathological condition comprising co-administering a therapeutically effective amount of a first compound, and a therapeutically effective amount of a second compound. In certain embodiments, the first compound or the second compound inhibits AB peptide polymerization; is an anti-inflammatory; improves cognitive function, mood, or social behavior; is associated with Tau or alpha-synuclein; or regulates amyloid peptide washout.

Claims

exact text as granted — not AI-modified
1 - 20 . (canceled) 
     
     
         21 . A method of treating a disease or condition in a subject in need thereof comprising co-administering a therapeutically effective amount of a first compound, and a therapeutically effective amount of a second compound, wherein the disease or condition is Alzheimer's disease, dementia, an amyloidosis-associated condition, or a head injury. 
     
     
         22 . A method of slowing the progression of a disease or condition in a subject in need thereof comprising co-administering a therapeutically effective amount of a first compound, and a therapeutically effective amount of a second compound, wherein the disease or condition is Alzheimer's disease, dementia, an amyloidosis-associated condition, or a head injury. 
     
     
         23 . The method of  claim 21 , wherein at least one of the first compound and the second compound is a compound inhibiting Aβ peptide polymerization, and the compound inhibiting Aβ peptide polymerization is selected from the group consisting of formula I-IV: 
       
         
           
           
               
               
           
         
         wherein, independently for each occurrence, 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are hydrogen, halo, azido, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, amino, alkylamino, arylamino, acylamino, heteroarylamino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, acyl, carboxyl, oxycarbonyl, acyloxy, silyl, thioether, sulfo, sulfonate, sulfonyl, sulfonamido, formyl, cyano, isocyano, or —Y-(haloalkylene)-alkyl; 
         R 7  is hydrogen, halo, azido, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, amino, alkylamine, arylamino, acylamino, heteroarylamino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, acyl, carboxyl, oxycarbonyl, acyloxy, silyl, thioether, sulfo, sulfonate, sulfonyl, sulfonamide, formyl, cyano, isocyano, —Y-(haloalkylene)-alkyl, or —Y-(haloalkylene)-R; 
         R N  is hydrogen, lower alkyl, or -(haloalkylene)-alkyl; 
         Y is a bond, N(R N ), O, or S; and 
       
       
         
           
           
               
               
           
         
         R is 
       
       
         
           
           
               
               
           
         
       
       provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , or R 10  is —Y-(haloalkylene)-alkyl; or R N  is -(haloalkylene)-alkyl. 
     
     
         24 . The method of  claim 22 , wherein at least one of the first compound and the second compound is a compound inhibiting Aβ peptide polymerization, and the compound inhibiting Aβ peptide polymerization is selected from the group consisting of formula I-IV: 
       
         
           
           
               
               
           
         
         wherein, independently for each occurrence, 
         R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are hydrogen, halo, azido, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, amino, alkylamino, arylamino, acylamino, heteroarylamino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, acyl, carboxyl, oxycarbonyl, acyloxy, silyl, thioether, sulfo, sulfonate, sulfonyl, sulfonamido, formyl, cyano, isocyano, or —Y-(haloalkylene)-alkyl; 
         R 7  is hydrogen, halo, azido, alkyl, haloalkyl, perhaloalkyl, fluoroalkyl, perfluoroalkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl, heteroaryl, aralkyl, heteroaralkyl, hydroxy, alkoxy, aryloxy, heteroaryloxy, aralkyloxy, heteroaralkyloxy, amino, alkylamine, arylamino, acylamino, heteroarylamino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, acyl, carboxyl, oxycarbonyl, acyloxy, silyl, thioether, sulfo, sulfonate, sulfonyl, sulfonamide, formyl, cyano, isocyano, —Y-(haloalkylene)-alkyl, or —Y-(haloalkylene)-R; 
         R N  is hydrogen, lower alkyl, or -(haloalkylene)-alkyl; 
         Y is a bond, N(R N ), O, or S; and 
       
       
         
           
           
               
               
           
         
         R is 
       
       
         
           
           
               
               
           
         
       
       provided that at least one of R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , or R 10  is —Y-(haloalkylene)-alkyl; or R N  is -(haloalkylene)-alkyl. 
     
     
         25 . The method of any of  claim 23 , the compound inhibiting Aβ peptide polymerization is 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method of any of  claim 25 , the compound inhibiting Aβ peptide polymerization is 
       
         
           
           
               
               
           
         
       
     
     
         27 . The method of any of  claim 24 , the compound inhibiting Aβ peptide polymerization is 
       
         
           
           
               
               
           
         
       
     
     
         28 . The method of any of  claim 27 , the compound inhibiting Aβ peptide polymerization is

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