Fumagillol type compounds and methods of making and using same

Abstract

The disclosure provides fumagillol type compounds and their use in treating medical disorders, such as obesity. Pharmaceutical compositions and methods of using, e.g. in the treatment of obesity are provided.

1 . A compound represented by: 
       
         
           
           
               
               
           
         
         wherein
 R 1  is H or C 1-3  alkyl; or a pharmaceutically acceptable salt or stereoisomer thereof. 
 
       
     
     
         2 . The compound of  claim 1 , represented by: 
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound represented by: 
       
         
           
           
               
               
           
         
         wherein
 R 2  is selected from the group consisting of H, hydroxyl, and isopropyl (optionally substituted with a hydroxyl); 
 R 3  is selected from the group consisting of H, and hydroxyl; or a pharmaceutically acceptable salt or stereoisomer thereof. 
 
       
     
     
         4 . A compound represented by: 
       
         
           
           
               
               
           
         
         wherein
 R′ is methyl; 
 R″ is H or methyl; or a pharmaceutically acceptable salt or stereoisomer thereof. 
 
       
     
     
         5 . A compound represented by: 
       
         
           
           
               
               
           
         
         wherein
 R 4  and R 5  are each methyl; or 
 R 4  and R 5 , together with the nitrogen to which they are attached, form a 4-5 membered ring optionally substituted by one or two substituents independently selected from the group consisting of methyl and hydroxyl; 
 or a pharmaceutically acceptable salt or stereoisomer thereof. 
 
       
     
     
         6 . The compound of  claim 5 , represented by: 
       
         
           
           
               
               
           
         
         wherein
 R 6  is selected from the group consisting of H, hydroxyl or methyl; and 
 R 7  is selected from the group consisting of H, hydroxyl or methyl. 
 
       
     
     
         7 . A compound represented by: 
       
         
           
           
               
               
           
         
         wherein
 n is 1 or 2; or a pharmaceutically acceptable salt or stereoisomer thereof. 
 
       
     
     
         8 . A compound selected from the group represented by: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or stereoisomer thereof. 
       
     
     
         9 . A compound selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         and a pharmaceutically acceptable salt or stereoisomer thereof. 
       
     
     
         10 . A method of treating and/or controlling obesity, comprising administering to a patient in need thereof an effective amount of the compound of  claim 9 . 
     
     
         11 . A method of inducing weight loss in a patient in need thereof, comprising administering to said patient an effective amount of the compound of  claim 9 . 
     
     
         12 . The method of  claim 10 , wherein the patient is a human. 
     
     
         13 . The method of  claim 10 , wherein the patient has a body mass index greater than or equal to about 25 kg/m 2  before the administration. 
     
     
         14 . The method  claim 10 , wherein the compound is administered orally, intravenously, or subcutaneously. 
     
     
         15 . The method of  claim 10 , wherein the compound is administered orally. 
     
     
         16 . A pharmaceutical composition comprising a compound of  claim 9 , and a pharmaceutically acceptable carrier. 
     
     
         17 . The composition of  claim 16 , wherein the composition is formulated as a unit dose. 
     
     
         18 . The method of  claim 10  comprising administering said compound in an amount insufficient to reduce angiogenesis in the patient.