Metabolites of N-(4-{[6,7-Bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide

Abstract

The invention relates to metabolites of cabozantinib (I) as well as uses thereof.

1 . An isolated metabolite of cabozantinib or a pharmaceutically acceptable salt thereof. 
     
     
         2 . The isolated metabolite of  claim 1  which is a compound selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein GA is a glucuronic acid moiety, or a pharmaceutically acceptable salt thereof. 
       
     
     
         3 . The isolated metabolite of  claim 2 , which is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         4 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         6 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The isolated metabolite of  claim 2  which is 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         12 . A method of treating a disease treating diseases or disorders associated with uncontrolled, abnormal, and/or unwanted cellular activities, the method comprising administering, to a mammal in need thereof, a therapeutically effective amount of a compound of  claims 1 - 11 , or a pharmaceutically acceptable salt thereof. 
     
     
         13 . A pharmaceutical composition comprising: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof and at least one pharmaceutically acceptable carrier. 
       
     
     
         14 . The composition of claim of  claim 13 , which is suitable for oral administration. 
     
     
         15 . A compound which is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein GA is a glucuronic acid moiety, or a pharmaceutically acceptable salt thereof. 
       
     
     
         16 . The compound of  claim 15 , which is selected from: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         17 . A method for identifying a metabolite of cabozantinib, comprising:
 administering cabozantinib to a mammal;   detecting or measuring a level or concentration of a metabolite of N-(4-{[6,7-bis(methyloxy)quinolin-4-yl]oxy}phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide in a mammal in tissues or bodily fluids of the mammal;   wherein the metabolite it selected from the group consisting of:   
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         wherein GA is a glucuronic acid moiety. 
       
     
     
         18 . The method of  claim 17 , wherein the metabolite is selected from; 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         19 . The method according to  claim 17 , wherein the bodily fluids are selected from the group consisting of plasma, bile, urine, and feces.