Methotrexate derivatives

Abstract

Antirheumatic agent containing as an active ingredient a compound resented by the following general formula (II): {where W is a group represented by the general formula: [where R 1 is a lower alkyl group having 1-4 carbon atoms; R 2 is a lower alkyl group having 1-4 carbon atoms or a trifluoromethyl group; R 3 is a hydrogen atom, a lower alkyl group having 1-4 carbon atoms or a trifluoromethyl group; R 4 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms: R 5 is a group represented by the general formula COOR 6 (where R 6 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms) or a group represented by the formula SO 3 H; and n is an integer of 1-4) or the general formula: {where R7 is a lower alkyl group having 1-4 carbon atoms; R 8 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 9 is a group represented by the general formula COOR 10 (where R 10 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms) or a group represented by the formula SO 3 H; and m is an integer of 1-4], or the general formula: [where R 11 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 12 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 13 is a group represent by the general formula COOR 14 (where R 14 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms) or a group represented by the formula SO 3 H; and l is an integer of 1 4], or the general formula: [where R 15 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 16 is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; and k is an integer of 2 or 3]}. All compounds represented by the general formula (II) 5 are novel except in the case where k is 2.

What is claimed is:  
     
         1 . A compound represented by the formula (I)  
       
         
           
           
               
               
           
         
       
       wherein W is represented by  
       
         
           
           
               
               
           
         
       
       where R 7  is a lower alkyl group having 1-4 carbon atoms; R 8  is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 9  is represented by the formula COOR 10  wherein R 10  is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms or R 9  is represented by the formula So 3 H; and m is an interger of 1-4, or 
 W is represented by  
                     
 where R 11  is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 12  is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms; R 13  is represented by the formula COOR 14  where R 14  is a hydrogen atom or a lower alkyl group having 1-4 carbon atoms or R 13  is represented by the formula SO 3 H; and l is an interger of 1-4.  
 
     
     
         2 . A compound according to  claim 1  wherein W is  
       
         
           
           
               
               
           
         
       
     
     
         3 . A compound according to  claim 1  wherein W is