Phosphonate analogs of hiv inhibitor compounds

Abstract

The invention is related to phosphorus substituted anti-viral inhibitory compounds, compositions containing such compounds, and therapeutic methods that include the administration of such compounds, as well as to processes and intermediates useful for preparing such compounds.

1 - 58 . (canceled) 
     
     
         59 . An in vivo metabolic product of a compound of Formula MBF-I or a pharmaceutically acceptable salt or ester thereof: 
       
         
           
           
               
               
           
         
         wherein B is hypoxanthinyl, K1 is cyclopentane ester of L-alanine, and K2 is OPh. 
       
     
     
         60 . The metabolic product of  claim 59  which is substantially isolated. 
     
     
         61 . A method of preparing the in vivo metabolic product of  claim 59  comprising contacting the compound of Formula MBF-I with a mammal for a period of time sufficient to yield the in vivo metabolic product. 
     
     
         62 . The method of  claim 61  wherein the mammal is a rat, mouse, guinea pig, monkey, or human. 
     
     
         63 . The method of  claim 61  wherein the compound of Formula MBF-I is orally administered to the mammal. 
     
     
         64 . The method of  claim 61  wherein the compound of Formula MBF-I is radiolabeled. 
     
     
         65 . The method of  claim 64  wherein the radiolabel comprises C 14  or H 3 . 
     
     
         66 . A method of determining the optimal therapeutic dose of the compound of Formula MBF-I in a mammal comprising measuring the quantity of the in vivo metabolic product of  claim 59  produced upon contacting the mammal with a radiolabeled the compound of Formula MBF-I and correlating the measured quantity of the in vivo metabolic product with therapeutic effectiveness of the compound of Formula MBF-I. 
     
     
         67 . A prodrug of a compound of Formula MBF-I: 
       
         
           
           
               
               
           
         
         Wherein B is hypoxanthinyl, K1 is cyclopentane ester of L-alanine, and K2 is OPh. 
       
     
     
         68 . A pharmaceutical composition comprising the prodrug of  claim 67 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient. 
     
     
         69 . 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 67 , or a pharmaceutically acceptable salt thereof. 
     
     
         70 . A solvate of a compound of Formula MBF I: 
       
         
           
           
               
               
           
         
         Wherein B is hypoxanthinyl, K1 is cyclopentane ester of L-alanine, and K2 is OPh. 
       
     
     
         71 . A pharmaceutical composition comprising the solvate of  claim 70 , or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier or excipient. 
     
     
         72 . 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 70 , or a pharmaceutically acceptable salt thereof.