Compounds and methods for inhibiting phosphate transport

Abstract

Compounds having activity as phosphate transport inhibitors, more specifically, inhibitors of intestinal apical membrane Na/phosphate co-transport, are disclosed. The compounds have the following structure (I): including stereoisomers, pharmaceutically acceptable salts and prodrugs thereof, wherein X, Y, A, R 1 and R 2 are as defined herein. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed.

1 . A compound having the following structure (I): 
       
         
           
           
               
               
           
         
       
       or a stereoisomer, prodrug or pharmaceutically acceptable salt thereof,
 wherein:
 A is —CR 1 — or —N—; 
 X is substituted aryl or substituted heteroaryl; 
 Y is halogen, optionally substituted alkylamino, optionally substituted alkoxy, optionally substituted thioalkyl, optionally substituted cycloalkyl, optionally substituted heterocyclyl, optionally substituted aryl, —O(optionally substituted cycloalkyl), —O(optionally substituted heterocyclyl) or —O(optionally substituted aryl); 
 each R 1  is, independently, hydrogen, halogen, C 1-6 alkyl or C 1-6 haloalkyl; 
 R 2  is —C(═O)NR 2a R 2b , —NR 2a C(═O)R 2b , —C(═O)R 2b , —NR 2a R 2b , —OR 2b  or —R 2b ; 
 R 2a  is hydrogen or optionally substituted C 1-6 alkyl; and 
 R 2b  is optionally substituted alkyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted heterocyclyl, optionally substituted heterocyclylalkyl, optionally substituted aryl, optionally substituted aralkyl, optionally substituted heteroaryl, or optionally substituted heteroarylalkyl. 
 
 
     
     
         2 - 32 . (canceled) 
     
     
         33 . A pharmaceutical composition comprising a compound of  claim 1 , or a stereoisomer, pharmaceutically acceptable salt or prodrug thereof, and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
         34 - 38 . (canceled) 
     
     
         39 . A method of inhibiting phosphate transport in a mammal, comprising administering to the mammal an effective amount of a compound of  claim 1  or a pharmaceutical composition of  claim 33 . 
     
     
         40 - 43 . (canceled) 
     
     
         44 . A method of treating hyperphosphatemia in a mammal in need thereof, comprising administering to the mammal an effective amount of a compound of  claim 1  or a pharmaceutical composition of  claim 33 .