Furanone derivative

Abstract

To provide a novel furanone derivative, and a medicine including the same. The furanone derivative is represented by the formula (I): wherein A represents —COOR1 or a hydrogen atom; R1 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocycle; R2 and R3 are the same or different and each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted phenyl group, an optionally substituted heterocycle, an optionally substituted heterocyclic fused ring, or an optionally substituted amino group; or alternatively, R2 and R3, taken together with the nitrogen atom to which they are attached, may form an optionally substituted heterocycle or an optionally substituted heterocyclic fused ring; and R4 represents a hydrogen atom or a halogen atom; with the proviso that when A represents —COOR1, R2 and R3 are not optionally substituted amino groups at the same time, and when A represents a hydrogen atom, R3 represents a hydrogen atom.

The invention claimed is: 
     
       1. A furanone derivative or a pharmaceutically acceptable salt thereof, represented by the formula (I):
 [Chemical Formula 1] 
 
       
         
           
           
               
               
           
         
       
       
        
         the formula (I-Z) or the formula (I-E): 
       
       
         
           
           
               
               
           
         
       
       
        
         wherein 
         A represents —COOR1 or a hydrogen atom; 
         R1 represents a hydrogen atom, an optionally substituted hydrocarbon group, or an optionally substituted heterocycle; 
         R2 and R3 are the same or different and each independently represent a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted phenyl group, an optionally substituted heterocycle, an optionally substituted heterocyclic fused ring, or an optionally substituted amino group; 
         or alternatively, R2 and R3, taken together with the nitrogen atom to which they are attached, form an optionally substituted heterocycle or an optionally substituted heterocyclic fused ring; 
         and R4 represents a hydrogen atom or a halogen atom; 
         with the proviso that when A represents —COOR1, R2 and R3 are not optionally substituted amino groups at the same time, and when A represents a hydrogen atom, R3 represents a hydrogen atom. 
       
     
     
       2. The furanone derivative or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein A is —COOR1. 
     
     
       3. The furanone derivative or a pharmaceutically acceptable salt thereof according to  claim 1 , wherein A is a hydrogen atom. 
     
     
       4. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein the furanone derivative or a pharmaceutically acceptable salt thereof is represented by the formula (II-Z) or formula (II-E): 
       
         
           
           
               
               
           
         
       
       
         
           
           
               
               
           
         
         wherein 
         A represents —COOR1 or a hydrogen atom; 
         R1 is selected from the group consisting of a hydrogen atom, an optionally substituted 1 to 6 carbon hydrocarbon group, and an optionally substituted 3 to 8 membered heterocycle; 
         R2 and R3, taken together with the nitrogen atom to which they are attached, form an optionally substituted 3 to 8 membered heterocycle or an optionally substituted 3 to 8 membered heterocyclic fused ring; 
         R4 represents a hydrogen atom or a halogen atom; 
         wherein any and all heterocyclic groups contain up to four heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen; 
         with the proviso that when A represents —COOR1, R2 and R3 are not optionally substituted amino groups at the same time, and when A represents a hydrogen atom, R3 represents a hydrogen atom.  
       
     
     
       5. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein any and all heterocyclic groups are optionally substituted 3 to 8 membered heterocycle groups that contain up to two heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen.  
     
     
       6. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein any and all hydrocarbon groups are 1 to 6 carbon hydrocarbon groups; and wherein any and all heterocyclic groups are optionally substituted 3 to 8 membered heterocycle groups that contain up to two heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen.  
     
     
       7. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 4, wherein A and R4 are both a hydrogen atom and R2 and R3 form a 3 to 8 membered heterocycle.  
     
     
       8. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 4, wherein A is —COOR1 where R1 is an optionally substituted 1 to 6 carbon hydrocarbon group, R4 is a hydrogen atom and R2 and R3 form a 3 to 8 membered heterocycle containing up to two heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen.  
     
     
       9. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is —COOR1 where R1 is an optionally substituted 1 to 6 carbon hydrocarbon group, R4 is a hydrogen atom and one of either of R2 and R3 is a hydrogen atom.  
     
     
       10. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is —COOR1 where R1 is an optionally substituted 1 to 6 carbon hydrocarbon group, R4 is a fluorine atom and one of either of R2 and R3 is a hydrogen atom.  
     
     
       11. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A and R4 are both a hydrogen atom, and one of either of R2 and R3 is a hydrogen atom.  
     
     
       12. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is —COOR1 where R1 is an optionally substituted 1 to 6 carbon hydrocarbon group, R4 is a hydrogen atom, one of either of R2 and R3 is a hydrogen atom and one of either of R2 and R3 is an optionally substituted amino group.  
     
     
       13. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is —COOR1 where R1 is an optionally substituted 1 to 6 carbon hydrocarbon group, R4 is a hydrogen atom, one of either of R2 and R3 is an optionally substituted 1 to 6 carbon hydrocarbon group and one of either of R2 and R3 is a 3 to 8 membered heterocycle containing up to two heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen.  
     
     
       14. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is —COOR1 where R1 is an optionally substituted 1 to 6 carbon hydrocarbon group, R4 is a hydrogen atom, one of either of R2 and R3 is a hydrogen atom and one of either of R2 and R3 is an optionally substituted 3 to 8 membered heterocyclic fused ring.  
     
     
       15. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein A is —COOR1 where R1 is a 3 to 8 membered heterocycle containing up to two heteroatoms selected from the group consisting of nitrogen, sulfur, and oxygen, R4 is a hydrogen atom and one of either of R2 and R3 is a hydrogen atom.  
     
     
       16. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein the furanone derivative or pharmaceutically acceptable salt thereof is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       
        
       
     
     
       17. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein the furanone derivative or pharmaceutically acceptable salt thereof is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       
        
       
     
     
       18. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein the furanone derivative or pharmaceutically acceptable salt thereof is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       
        
       
     
     
       19. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 1, wherein the pharmaceutically acceptable salt is the hydrochloride or p-toluenesulfonate salt.  
     
     
       20. The furanone derivative or a pharmaceutically acceptable salt thereof according to claim 16, wherein the pharmaceutically acceptable salt is the hydrochloride or p-toluenesulfonate salt.