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 diagnostic assay for determining a therapeutic dose in a mammal of a compound of formula IB: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof, wherein, 
         L 2  is a covalent bond, —C(R 6 ) 2 — or —C(O)—; 
         Z 1  is —O— or —N(R 7 )—; 
         R 6  is selected from the group consisting of H, alkyl, substituted alkyl, and heteroalkyl; 
         R 7  is selected from the group consisting of H, alkyl, substituted alkyl, heteroalkyl, carbocyclyl, substituted carbocyclyl, heterocyclyl, and substituted heterocyclyl; and 
         R 8  and R 9  are each one or more substituents independently selected from the group consisting of H, alkyl, substituted alkyl, halogen, aryl, substituted aryl, heterocyclyl, substituted heterocyclyl, and —CN; 
         the diagnostic assay comprising 
         a) administering to the mammal a radiolabeled compound of formula IB, 
         b) measuring the quantity of a metabolic product of the radiolabeled compound of formula IB; and 
         c) determining the therapeutic dose of a compound of formula IB for the mammal. 
       
     
     
         22 : The diagnostic assay of  claim 21 , wherein the radiolabeled compound of Formula IB comprises C 14 . 
     
     
         23 : The diagnostic assay of  claim 21 , wherein the radiolabeled compound of formula IB comprises H 3 . 
     
     
         24 : The diagnostic assay of  claim 21 , wherein the metabolic product results from a physiological pathway selected from the group consisting of oxidation, reduction, hydrolysis, amidation, and esterification.