Small-molecule hsp90 inhibitors

Abstract

Purine scaffold Hsp90 inhibitors are useful in therapeutic applications and as radioimaging ligands.

1 - 35 . (canceled) 
     
     
         36 . A method of preparing a compound of formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof; 
         the method comprising a step using IN-2: 
       
       
         
           
           
               
               
           
         
         as a reactant, 
         wherein:
 X 3  is hydrogen or halogen; 
 X 1  is a C 1  to C 10  saturated or unsaturated moiety containing up to 10 carbon atoms and at least one heteroatom; 
 the linker is S; 
 X 2  is halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, COO-alkyl, NH 2 , OH, CN, SO 2 X 7 , NO 2 , NO, C═SR 2a , NHSO 2 X 7 , or C═OR 2a , where X 7  is F, NH 2 , alkyl or H, and R 2a  is alkyl, NH 2 , NH-alkyl or O-alkyl; and 
 n is 1 or 2. 
 
       
     
     
         37 . The method of  claim 36 , wherein the method comprises a step that includes a Mitsunobu reaction. 
     
     
         38 . The method of  claim 36 , wherein the method comprises a step carried out in the presence of PPh 3  and an azodicarboxylate. 
     
     
         39 . The method of  claim 37 , wherein the method comprises a step carried out in the presence of PPh 3  and an azodicarboxylate. 
     
     
         40 . The method of  claim 37 , wherein the X 2  is halogen, alkyl, alkylamino, or dialkylamino. 
     
     
         41 . The method of  claim 38 , wherein the X 2  is halogen, alkyl, alkylamino, or dialkylamino. 
     
     
         42 . The method of  claim 39 , wherein the X 2  is halogen, alkyl, alkylamino, or dialkylamino. 
     
     
         43 . The method of  claim 40 , wherein X 1  is a C 1  to C 10  alkyl, alkenyl, or alkynyl group, wherein the alkyl, alkenyl, or alkynyl group includes a nitrogen atom. 
     
     
         44 . The method of  claim 41 , wherein X 1  is a C 1  to C 10  alkyl, alkenyl, or alkynyl group, wherein the alkyl, alkenyl, or alkynyl group includes a nitrogen atom. 
     
     
         45 . The method of  claim 42 , wherein X 1  is a C 1  to C 10  alkyl, alkenyl, or alkynyl group, wherein the alkyl, alkenyl, or alkynyl group includes a nitrogen atom. 
     
     
         46 . The method of  claim 43 , wherein the linker is —S—. 
     
     
         47 . The method of  claim 44 , wherein the linker is —S—. 
     
     
         48 . The method of  claim 45 , wherein the linker is —S—. 
     
     
         49 . The method of  claim 46 , wherein n is 1. 
     
     
         50 . The method of  claim 47 , wherein n is 1. 
     
     
         51 . The method of  claim 48 , wherein nisi. 
     
     
         52 . The method of  claim 36 , wherein the compound is: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof.