Substituted Quinazolinones For Inhibiting PI3K

Abstract

The present invention relates to novel quinazolinone derivatives inhibiting PI3K; a method for preparing the derivatives; and a pharmaceutical composition for treating hematologic neoplasms or liver diseases, containing the quinazolinone derivatives, wherein the novel quinazolinone derivatives according to the present invention have a beneficial effect in the treatment of hematologic neoplasms or liver diseases. Particularly, the quinazolinone derivatives inhibit PI3Kδ with high selectivity compared to that of a conventional anticancer drug of PI3Kδ inhibitors, thereby significantly reducing immunotoxicity, or simultaneously inhibit PI3Kδ and PI3Kγ, thereby enabling the treatment of autoimmune diseases, and anticancer therapy for blood cancer and the like. These targeted drugs have an advantage of enabling the problem of side effects of a conventional highly toxic anticancer therapy to be resolved.

1 - 5 . (canceled) 
     
     
         6 . A method of preparing a compound of Formula 1, the method comprising:
 preparing a compound of Formula 2;   preparing a compound of Formula 3; and   reacting a compound of Formula 2 with a compound of Formula 3 to prepare the compound of Formula 1:   
       
         
           
           
               
               
           
         
         wherein, in Formula 1, 
         X is —H, halogen, or —CH 3 ; and 
         Y is C 3-4  cycloalkyl, 
       
       
         
           
           
               
               
           
         
         wherein, in Formula 2, 
         X is —H, halo, or —CH 3 ; and 
         Y is C 3-4  cycloalkyl, 
       
       
         
           
           
               
               
           
         
         wherein, in Formula 3, 
         Z is halo. 
       
     
     
         7 . The method according to  claim 6 , wherein the preparing the compound of Formula 2 comprises:
 preparing a compound of Formula 4, and   deprotecting the compound of Formula 4 to prepare the compound of Formula 2;   
       
         
           
           
               
               
           
         
         wherein, in Formula 4, 
         X is —H, halogen, or —CH 3 ; and 
         Y is C 3-4  cycloalkyl, 
         R is C 1-6  alkyl, phenyl, or benzyl. 
       
     
     
         8 . The method according to  claim 6 , wherein R is tertiary butyl or benzyl. 
     
     
         9 . The method according to  claim 6 , wherein the preparing the compound of Formula 4 comprises:
 preparing a compound of Formula 5,   preparing a compound of Formula 6,   reacting the compound of Formula 5 with the compound of Formula 6 to prepare the compound of Formula 4,   
       
         
           
           
               
               
           
         
         wherein, in Formula 2, 
         X is —H, halo, or —CH 3   
       
       
         
           
           
               
               
           
         
         wherein, in Formula 3, 
         Y is C 3-4  cycloalkyl 
         R is C 1-6  alkyl, phenyl, or benzyl. 
       
     
     
         10 . The method according to  claim 9 , wherein R is tertiary butyl or benzyl.