Pyrazolopyrimidinone kinase inhibitor

Abstract

The present invention provides a novel pyrazolo[3,4-d]pyrimidin-4-one, specifically a derivative of 1-(pyridine-4-yl)-pyrazolo[3,4-d]pyrimidin-4-one. This compound is a kinase inhibitor that shows unexpected anti-proliferative activity against cells, including against tumor cells, and anti-tumor activity in xenograft tumor models. The compound or a suitable salt or prodrug thereof is useful for the treatment of individuals suffering from a cancer or another proliferative disorder or disease.

1 . A packaged pharmaceutical product, comprising a pharmaceutical composition comprising a compound having the structure of Formula (1): 
       
         
           
           
               
               
           
         
       
       or a tautomer or pharmaceutically acceptable salt thereof, and instructions for administering said pharmaceutical composition to an individual in need thereof. 
     
     
         2 . The packaged pharmaceutical product of  claim 1 , wherein said instructions are for administering said pharmaceutical composition to an individual suffering from a cancer. 
     
     
         3 . The packaged pharmaceutical product of  claim 2 , wherein said individual is a human. 
     
     
         4 . A method for treating an individual suffering from a cancer, comprising administering to said individual an active ingredient comprising a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         5 . The method of  claim 4 , wherein said individual is a mammal selected from the group consisting of: domestic mammals, rodents, and humans. 
     
     
         6 . A method for killing or inhibiting the proliferation or growth of a tumor cell, comprising contacting said tumor cell with a compound of Formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         7 . The method of  claim 6 , wherein said tumor cell is a malignant cell in an individual. 
     
     
         8 . The method of  claim 7 , wherein said individual is a mammal selected from the group consisting of: domestic mammals, rodents, and humans. 
     
     
         9 . The method of  claim 6 , wherein said tumor cell is exposed to said compound or said pharmaceutically acceptable salt thereof in vitro. 
     
     
         10 . A method of treating an individual suffering from a disorder or disease associated with the activity of one or more cyclin dependent kinases selected from: CDK1, CDK2, CDK4, CDK7 and CDK9, comprising administering to said individual an active ingredient comprising a compound of Formula (1): 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 10 , wherein said disorder or disease is a cancer. 
     
     
         12 . The method of  claim 10 , wherein said disorder is associated with the activity of CDK9. 
     
     
         13 . The method of  claim 10 , wherein said individual is a mammal selected from the group consisting of: domestic mammals, rodents, and humans. 
     
     
         14 . A method of synthesizing a compound of formula (I): 
       
         
           
           
               
               
           
         
       
       or optionally a salt thereof, comprising reacting a compound having the structure of formula (II) with a compound having the structure of formula (III), 
       
         
           
           
               
               
           
         
       
       wherein X is selected from —O-alkyl, —O-alkenyl, —O-alkynyl, —O-acyl, and halogen; and, optionally, reacting the resultant compound with an acid to make an acid salt. 
     
     
         15 . The method of  claim 14 , wherein X is —OEt. 
     
     
         16 . A method of synthesizing the pharmaceutically acceptable salt of a compound of formula (1): 
       
         
           
           
               
               
           
         
       
       comprising the step of reacting the compound with an acid. 
     
     
         17 . The method of  claim 16 , wherein the acid is hydrochloric acid or maleic acid.