Bicyclo-substituted pyrazolon azo derivatives, preparation process and pharmaceutical use thereof

Abstract

The bicyclo-substituted pyrazolon-azo derivatives of formula (I) or pharmaceutical acceptable salts, hydrates or solvates thereof, methods for their preparation, pharmaceutical compositions containing the same and their use as a therapeutic agent, especially as thrombopoietin (TPO) mimetics and their use as agonists of thrombopoietin receptor are disclosed. The definition of substituents in formula (I) are the same as defined in the description.

1 - 13 . (canceled) 
     
     
         14 . A compound of formula (IA) 
       
         
           
           
               
               
           
         
         wherein:
 A is selected from the group consisting of carbon and oxygen; 
 R 5 , R 6 , and R 7  are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, halogen, hydroxyl, amino, nitro, cyano, carboxylic acid, and carboxylic ester; 
 R 8 , R 9 , R 10 , and R 11  are each independently selected from the group consisting of hydrogen and alkyl, wherein R 8 , R 9 , R 10 , and R 11  can substitute any open valence of the ring to which they attach; and 
 n is 0, 1, or 2. 
 
       
     
     
         15 . The compound according to  claim 14 , wherein R 5 , R 6 , and R 7  are hydrogen. 
     
     
         16 . The compound according to  claim 14 , wherein R 8 , R 9 , R 10 , and R 11  are each independently hydrogen, methyl, and ethyl. 
     
     
         17 . The compound according to  claim 14 , which is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         18 . A process for preparing the compound of  claim 14 , comprising: 
       
         
           
           
               
               
           
         
         converting an amino substituted benzocycle of formula (IA_a), in the presence of a carbonyl compound, to the corresponding compound of formula (IA). 
       
     
     
         19 . The process according to  claim 18 , wherein the converting step comprises converting the amino substituted benzocycle of formula (IA_a) to the corresponding diazo substituted benzocycle; 
       
         
           
           
               
               
           
         
         reducing the diazo substituted benzocycle to obtain a hydrazine of formula (IA_b); and 
         coupling the hydrazine of formula (IA_b) with the carbonyl compound to obtain the compound of formula (IA).