2-Amino-7,8-dihydro-6H-pyrido[4,3-D]pyrimidin-5-ones

Abstract

Disclosed are 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, their stereoisomers, tautomers, pharmaceutically acceptable salts, and prodrugs thereof; compositions that include a pharmaceutically acceptable carrier and one or more of the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent. Disclosed also are methods of using the 2-amino-7,8-dihydro-6H-pyrido[4,3-d]pyrimidin-5-one compounds, either alone or in combination with at least one additional therapeutic agent, in the prophylaxis or treatment of cellular proliferative, viral, autoimmune, cardiovascular, and central nervous system diseases.

1 - 22 . (canceled) 
     
     
         23 . A method for treating a condition by modulating HSP90 activity comprising administering to a human or animal subject in need of such treatment an effective amount of a compound, a stereoisomer, tautomer, oxide, or ester of Formula (I) or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
       
       effective to inhibit HSP90 activity in the human or animal subject, wherein
 R a  is selected from the group consisting of
 (1) hydrogen, 
 (2) halogen, 
 (3) hydroxyl, 
 (4) C 1 -C 6  alkoxy, 
 (5) thiol, 
 (6) C 1 -C 6  alkylthiol, 
 (7) substituted or unsubstituted C 1 -C 6  alkyl, 
 (8) amino or substituted amino, 
 (9) substituted or unsubstituted aryl, 
 (10) substituted or unsubstituted heteroaryl, and 
 (11) substituted or unsubstituted heterocyclyl; 
 
 R is selected from the group consisting of
 (1) hydrogen, 
 (2) substituted or unsubstituted C 1 -C 6  alkyl, 
 (3) substituted or unsubstituted C 2 -C 6  alkenyl, 
 (4) substituted or unsubstituted C 2 -C 6  alkynyl, 
 (5) substituted or unsubstituted C 3 -C 7  cycloalkyl, 
 (6) substituted or unsubstituted C 5 -C 7  cycloalkenyl. 
 (7) substituted or unsubstituted aryl, 
 (8) substituted or unsubstituted heteroaryl, and 
 (9) substituted or unsubstituted heterocyclyl; 
 
 R b  is selected from the group consisting of
 (1) substituted or unsubstituted C 3 -C 7  cycloalkyl, 
 (2) substituted or unsubstituted C 5 -C 7  cycloalkenyl, 
 (3) substituted or unsubstituted aryl, 
 (4) substituted or unsubstituted heteroaryl, and 
 (5) substituted or unsubstituted heterocyclyl; and 
 
 
       with the proviso that when R a  is amino, then R b  is not phenyl, 4-alkyl-phenyl, 4-alkoxy-phenyl, or 4-halo-phenyl. 
     
     
         24 . The method of  claim 23 , wherein the condition is cancer. 
     
     
         25 . A method for preparing a compound of formula (I) or a stereoisomer, tautomer, pharmaceutically acceptable salt, or prodrug thereof, comprising
 (a) reacting a compound of formula (I) with an acid to form an acid addition salt; or   (b) reacting an acid addition salt of formula (I) to form a free base compound of formula (I); or   (c) reacting an intermediate compound of formula (VI) with guanidine or a guanidine derivative   
       
         
           
           
               
               
           
         
       
       wherein R a , R, and R b  are as defined for formula (I) and W is O or NR′R″ where R′ and R″ are independently H or alkyl to form a compound of formula (I). 
     
     
         26 . The intermediate compound of  claim 25  having formula (VI). 
     
     
         27 . The intermediate compound of  claim 26  wherein R a  is methyl. 
     
     
         28 . The intermediate compound of  claim 26  having formula (VII) 
       
         
           
           
               
               
           
         
       
       wherein
 R is as defined for formula (VI); 
 R 5  is hydrogen or halo; and R 6a  is selected from the group consisting of halo, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.