Modulators of pharmacokinetic properties of therapeutics

Abstract

The present application provides for a compound of Formula I, or a pharmaceutically acceptable salt, solvate, and/or ester thereof, compositions containing such compounds, therapeutic methods that include the administration of such compounds, and therapeutic methods and include the administration of such compounds with at least one additional therapeutic agent.

1 - 20 . (canceled) 
     
     
         21 . A method of preparing Compound 19: 
       
         
           
           
               
               
           
         
       
       comprising reacting Compound 17 
       
         
           
           
               
               
           
         
       
       with Compound 18 
       
         
           
           
               
               
           
         
       
     
     
         22 . The method of  claim 21 , wherein the reaction is performed in the presence of a strong base. 
     
     
         23 . The method of  claim 21 , further comprising performing an elimination reaction of Compound 19 to provide Compound 20 
       
         
           
           
               
               
           
         
       
     
     
         24 . The method of  claim 23 , wherein the elimination reaction is performed in the presence of a reductant. 
     
     
         25 . The method of  claim 23 , further comprising removing the benzyl protecting group of Compound 20 to provide Compound 21 
       
         
           
           
               
               
           
         
       
     
     
         26 . The method of  claim 25 , wherein the deprotection reaction is performed in the presence of sodium. 
     
     
         27 . The method of  claim 25 , further comprising reducing Compound 21 to provide Compound 22 
       
         
           
           
               
               
           
         
       
     
     
         28 . The method of  claim 27 , wherein the reduction is performed in the presence of hydrogenation catalyst. 
     
     
         29 . The method of  claim 28 , wherein the hydrogenation catalyst is Pd/C. 
     
     
         30 . The method of  claim 27 , further comprising reacting Compound 22 with Compound 16 
       
         
           
           
               
               
           
         
       
       to provide Compound 88