Modulators of pharmacokinetic properties of therapeutics

Abstract

The present application provides for a compound of Formula IV, 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 - 41 . (canceled) 
     
     
         42 . An in vivo metabolic product of Compound P: 
       
         
           
           
               
               
           
         
       
     
     
         43 . The metabolic product of  claim 42  which is substantially isolated. 
     
     
         44 . A method of preparing the in vivo metabolic product of  claim 42  comprising contacting Compound P with a mammal for a period of time sufficient to yield the in vivo metabolic product. 
     
     
         45 . The method of  claim 44  wherein the mammal is a rat, mouse, guinea pig, monkey, or human. 
     
     
         46 . The method of  claim 44  wherein Compound P is orally administered to the mammal. 
     
     
         47 . The method of  claim 44  wherein Compound P is radiolabeled. 
     
     
         48 . The method of  claim 47  wherein the radiolabel comprises C 14  or H 3 . 
     
     
         49 . A method of determining the optimal therapeutic dose of Compound P in a mammal comprising measuring the quantity of the in vivo metabolic product of  claim 42  produced upon contacting the mammal with a radiolabeled Compound P and correlating the measured quantity of the in vivo metabolic product with therapeutic effectiveness of Compound P. 
     
     
         50 . A prodrug of Compound P: 
       
         
           
           
               
               
           
         
       
     
     
         51 . The prodrug of  claim 50  which is an ester of Compound P. 
     
     
         52 . A pharmaceutical composition comprising the prodrug of  claim 50 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient. 
     
     
         53 . A method of improving the pharmacokinetics of a drug, comprising administering to a patient treated with said drug, a therapeutically effective amount of the prodrug of  claim 50 , or a pharmaceutically acceptable salt thereof. 
     
     
         54 . A solvate of Compound P: 
       
         
           
           
               
               
           
         
       
     
     
         55 . A pharmaceutical composition comprising the solvate of  claim 54 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient. 
     
     
         56 . A method of improving the pharmacokinetics of a drug, comprising administering to a patient treated with said drug, a therapeutically effective amount of the solvate of  claim 54 , or a pharmaceutically acceptable salt thereof.