4-methylsulfonyl-substituted piperidine urea compounds

Abstract

The present invention provides novel 4-methylsulphone-substituted piperidine urea compounds that are useful for the treatment of dilated cardiomyopathy (DCM) and conditions associated with left and/or right ventricular systolic dysfunction or systolic reserve. The synthesis and characterization of the compounds is described, as well as methods for treating DCM and other forms of heart disease.

1 - 35 . (canceled) 
     
     
         36 . A method for preparing a compound having the formula: 
       
         
           
           
               
               
           
         
         the method comprising: 
         reacting a compound 
       
       
         
           
           
               
               
           
         
         
           with sodium periodate to produce a compound 
         
       
       
         
           
           
               
               
           
         
         reacting the compound 
       
       
         
           
           
               
               
           
         
         
           with lithium diisopropylamide (LDA) followed by N-Fluorobenzenesulfonimide (NFSI) to produce a compound 
         
       
       
         
           
           
               
               
           
         
         reacting the compound 
       
       
         
           
           
               
               
           
         
         
           with iodomethane to produce a compound 
         
       
       
         
           
           
               
               
           
         
         
            and 
         
         reacting the compound 
       
       
         
           
           
               
               
           
         
         
           with n-Butyllithium to produce the compound 
         
       
       
         
           
           
               
               
           
         
       
     
     
         37 . The method of  claim 36 , further comprising:
 reacting a compound   
       
         
           
           
               
               
           
         
         
           with a compound 
         
       
       
         
           
           
               
               
           
         
         
           to produce a compound 
         
       
       
         
           
           
               
               
           
         
         reacting the compound 
       
       
         
           
           
               
               
           
         
         
           with diethylaminosulfur trifluoride (DAST) to produce a compound 
         
       
       
         
           
           
               
               
           
         
         
            and 
         
         reacting the compound 
       
       
         
           
           
               
               
           
         
       
       with N-butyllithium and perchloroethane to produce the compound 
       
         
           
           
               
               
           
         
       
     
     
         38 . A compound selected from the group consisting of 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         39 . The compound of  claim 38 , which is 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         40 . The compound of  claim 38 , which is 
       
         
           
           
               
               
           
         
         or a salt thereof. 
       
     
     
         41 . The compound of  claim 38 , which is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a salt thereof.