Radicicol derivatives

Abstract

Radicicol derivatives represented by the following formula (I) having tyrosine kinase inhibition activity or pharmacologically acceptable salts thereof: wherein R 1 and R 2 are the same or different, and each represents hydrogen, alkanoyl, alkenoyl, tert-butyldiphenylsilyl or tert-butyldimethylsilyl; R 3 represents Y—R 5 {wherein Y represents substituted or unsubstituted alkylene; and R 5 represents CONR 6 R 7 (wherein R 6 represents hydrogen, hydroxyl, substituted or unsubstituted lower alkyl, substituted or unsubstituted higher alkyl, and the like; R 7 represents hydroxyl, substituted lower alkyl, and the like), CO 2 R 12 (wherein R 12 represents substituted lower alkyl, substituted or unsubstituted higher alkyl, and the like), and the like} and the like; X represents halogen or is combined together with R 4 to represent a single bond; and R 4 is combined together with X to represent a single bond, or represents hydrogen, alkanoyl, and the like.

What is claimed is:  
     
         1 . A radicicol derivative represented by the following formula (I) or a pharmacologically acceptable salt thereof:  
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are the same or different, and each represents hydrogen, alkanoyl, alkenoyl, tert-butyldiphenylsilyl or tert-butyldimethylsilyl;  
         R 3  represents:  
         Y—R 5  {wherein Y represents substituted or unsubstituted alkylene; and R 5  represents CONR 6 R 7  (wherein R 6  represents hydrogen, hydroxyl, substituted or unsubstituted lower alkyl, substituted or unsubstituted higher alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclic group, or NR 8 R 9  (wherein R 8  and R 9  are the same or different, and each represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted higher alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclic group, substituted or unsubstituted alkanoyl, substituted or unsubstituted aroyl, carbonyl bound to a substituted or unsubstituted heterocyclic ring, or substituted or unsubstituted arylcarbamoyl), or is combined together with R 7  and adjoining N to represent a substituted or unsubstituted heterocyclic group; and R 7  is combined together with R 6  and adjoining N to represent a substituted or unsubstituted heterocyclic group, or represents hydroxyl, substituted lower alkyl, substituted or unsubstituted higher alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted lower alkoxy, substituted or unsubstituted aryl, a substituted or unsubstituted heterocyclic group, or NR 10 R 11  (wherein R 10  and R 11  have the same meaning as R 8  and R 9  defined above, respectively)), CO 2 R 12  (wherein R 12  represents substituted lower alkyl, substituted or unsubstituted higher alkyl, substituted or unsubstituted lower cycloalkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted aryl, or a substituted or unsubstituted heterocyclic group), substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyridonyl, substituted or unsubstituted pyrrolidonyl, substituted or unsubstituted uracilyl, substituted or unsubstituted piperidyl, substituted or unsubstituted piperidino, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted morpholino, substituted or unsubstituted morpholinyl, substituted or unsubstituted piperazinyl, substituted or unsubstituted thiomorpholino, or substituted or unsubstituted dioxolanyl}, COR 13  (wherein R 13  represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted higher alkyl, substituted or unsubstituted aryl, substituted or unsubstituted lower alkoxy, or NR 14 R 15  (wherein R 14  and R 15  are the same or different, and each represents hydrogen, substituted or unsubstituted lower alkyl, substituted or unsubstituted higher alkyl, substituted or unsubstituted aryl, or substituted or unsubstituted pyridyl, or R 14  and R 15  are combined together with adjoining N to represent a substituted or unsubstituted heterocyclic group)), or  
         substituted or unsubstituted aryl;  
         X represents halogen, or is combined together with R 4  to represent a single bond; and  
         R 4  is combined together with X to represent a single bond, or represents hydrogen, alkanoyl, alkenoyl, or —SO-Z {wherein Z represents formula (A):  
         
           
             
             
                 
                 
             
           
         
         wherein R 1A  and R 2A  have the same meaning as R 1  and R 2  defined above, respectively; X A  represents halogen; and W represents O or N—O—R 3A  (wherein R 3A  has the same meaning as R 3  defined above)}.  
       
     
     
         2 . The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein X is halogen.  
     
     
         3 . The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein X is combined together with R 4  to represent a single bond.  
     
     
         4 . The compound according to  claim 3  or a pharmacologically acceptable salt thereof, wherein R 1  and R 2  each is hydrogen.  
     
     
         5 . The compound according to  claim 4  or a pharmacologically acceptable salt thereof, wherein R 3  is Y—R 5 .  
     
     
         6 . The compound according to  claim 5  or a pharmacologically acceptable salt thereof, wherein R 5  is substituted or unsubstituted aryl, substituted or unsubstituted pyridyl, substituted or unsubstituted pyridonyl, substituted or unsubstituted pyrrolidonyl, substituted or unsubstituted uracilyl, substituted or unsubstituted piperidyl, substituted or unsubstituted piperidino, substituted or unsubstituted pyrrolidinyl, substituted or unsubstituted morpholino, substituted or unsubstituted morpholinyl, substituted or unsubstituted piperazinyl., substituted or unsubstituted thiomorpholino, or substituted or unsubstituted dioxolanyl.  
     
     
         7 . The compound according to  claim 5  or a pharmacologically acceptable salt thereof, wherein R 5  is pyrrolidonyl.  
     
     
         8 . A therapeutic agent of diseases caused by tyrosine kinase, which comprises at least one of the compounds according to any one of  claims 1  to  6  or a pharmacologically acceptable salt thereof.