Antiallergic

Abstract

A medicament for the preventive and/or therapeutic treatment of allergic diseases and/or endometriosis and/or hysteromyoma which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof: wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted), A represents hydrogen atom or acetyl group, E represents an aryl group which may be substituted or a hetero aryl group which may be substituted, ring Z represents an arene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above.

1 . A medicament for the preventive and/or therapeutic treatment of an allergic disease and/or endometriosis and/or hysteromyoma, which comprises as an active ingredient a substance selected from the group consisting of a compound represented by the following general formula (I) and a pharmacologically acceptable salt thereof, and a hydrate thereof and a solvate thereof:  
     
       
         
         
             
             
         
       
       wherein X represents a connecting group whose number of atoms in the main chain is 2 to 5 (said connecting group may be substituted),  
       A represents hydrogen atom or acetyl group,  
       E represents an aryl group which may be substituted or a heteroaryl group which may be substituted,  
       ring Z represents an arene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above, or a heteroarene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined above and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined above.  
     
   
   
       2 . The medicament according to  claim 1 , wherein X is a group selected from the following connecting group α (said group may be substituted): [Connecting Group α] The groups of the following formulas:  
     
       
         
         
             
             
         
       
       wherein a bond at the left end binds to ring Z and a bond at the right end binds to E.  
     
   
   
       3 . The medicament according to  claim 2 , wherein X is a group represented by the following formula (said group may be substituted):  
     
       
         
         
             
             
         
       
       wherein a bond at the left end binds to ring Z and a bond at the right end binds to E.  
     
   
   
       4 . The medicament according to  claim 1 , wherein A is a hydrogen atom.  
   
   
       5 . The medicament according to  claim 1 , wherein ring Z is a C 6  to C 10  arene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I), or a 5 to 1 3-membered heteroarene which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I).  
   
   
       6 . The medicament according to  claim 5 , wherein ring Z is a ring selected from the following ring group β: 
 [Ring Group β] benzene ring, naphthalene ring, thiophene ring, pyridine ring, indole ring, quinoxaline ring, and carbazole ring wherein said ring may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I).    
   
   
       7 . The medicament according to clam  6 , wherein ring Z is a benzene ring which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I).  
   
   
       8 . The medicament according to  claim 7 , wherein ring Z is a benzene ring which is substituted with halogen atom(s) in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I).  
   
   
       9 . The medicament according to  claim 6 , wherein ring Z is a naphthalene ring which may have one or more substituents in addition to the group represented by formula —O-A wherein A has the same meaning as that defined in the general formula (I) and the group represented by formula —X-E wherein each of X and E has the same meaning as that defined in the general formula (I).  
   
   
       10 . The medicament according to  claim 1 , wherein E is a C 6  to C 10  aryl group which may be substituted or a 5 to 13-membered heteroaryl group which may be substituted.  
   
   
       11 . The medicament according to  claim 10 , wherein E is a phenyl group which may be substituted.  
   
   
       12 . The medicament according to  claim 11 , wherein E is 3,5-bis(trifluoromethyl)phenyl group.  
   
   
       13 . The medicament according to  claim 10 , wherein E is a 5-membered heteroaryl group which may be substituted.  
   
   
       14 . The medicament according to  claim 1 , having inhibitory activity against production of IgE, inhibitory activity against degranulation from activated a mast cell, and/or inhibitory activity against proliferation of a mast cell.  
   
   
       15 . A compound represented by the general formula (I-1) or a salt thereof, or a hydrate thereof or a solvate thereof:  
     
       
         
         
             
             
         
       
       wherein Z 1  represents 2-hydroxyphenyl group which may be substituted in the 5-position or 2-acetoxyphenyl group which may be substituted in the 5-position, and E 1  represents a phenyl group which may be substituted.  
     
   
   
       16 . The compound according to  claim 15  or a salt thereof, or a hydrate thereof or a solvate thereof, wherein E 1  is 2,5-bis(trifluoromethyl)phenyl group or 3,5-bis(trifluoromethyl)phenyl group, provided that the following compounds are excluded: 
 N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxybenzamide,    N-[3,5-bis(trifluoromethyl)phenyl]-5-chloro-2-hydroxybenzamide,    N-[3,5-bis(trifluoromethyl)phenyl]-5-bromo-2-hydroxybenzamide,    N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-5-iodobenzamide, and    N-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxy-5-nitrobenzamide.    
   
   
       17 . The compound according to  claim 16  or a salt thereof, or a hydrate thereof or a solvate thereof, wherein Z 1  is 2-hydroxyphenyl group which is substituted with a halogen atom in the 5-position or 2-acetoxyphenyl group which is substituted with a halogen atom in the 5-position.  
   
   
       18 . A compound represented by the general formula (I-2) or a salt thereof, or a hydrate thereof or a solvate thereof:  
     
       
         
         
             
             
         
       
       wherein Z 2  represents 2-hydroxyphenyl group which may be substituted in the 5-position or 2-acetoxyphenyl group which may be substituted in the 5-position, E 2  represents a 2,5-di-substituted phenyl group wherein one of said substituents is trifluoromethyl group or a 3,5-di-substituted phenyl group wherein one of said substituents is trifluoromethyl group, provided that the following compounds are excluded:  
       5-chloro-N-[5-chloro-3-(trifluoromethyl)phenyl]-2-hydroxybenzamide,  
       5-fluoro-2-hydroxy-N-[2-(2,2,2-trifluoroethoxy)-5-(trifluoromethyl)phenyl]benzamide,  
       5-fluoro-2-hydroxy-N-[2-(6,6,6-trifluorohexyloxy)-5-(trifluoromethyl)phenyl]benzamide,  
       5-chloro-N-[2-(4-chlorophenoxy)-5-(trifluoromethyl)phenyl]-2-hydroxybenzamide,  
       5-chloro-2-hydroxy-N-[2-(4-methylphenoxy)-5-(trifluoromethyl)phenyl]benzamide,  
       5-chloro-N-[2-(4-chlorophenyl)sulfanyl-5-(trifluoromethyl)phenyl]-2-hydroxybenzamide,  
       5-chloro-2-hydoxy-N-[2-(1-naphthyloxy)-5-(trifluoromethyl)phenyl]benzamide, and  
       5-chloro-2-hydoxy-N-[2-(2-naphthyloxy)-5-(trifluoromethyl)phenyl]benzamide.  
     
   
   
       19 . The compound according to  claim 18  or a salt thereof, or a hydrate thereof or a solvate thereof, wherein Z 2  is 2-hydroxyphenyl group which is substituted with a halogen atom in the 5-position or 2-acetoxyphenyl group which is substituted with a halogen atom in the 5-position.  
   
   
       20 . The compound represented by the general formula (I-3) or a salt thereof, or a hydrate thereof or a solvate thereof:  
     
       
         
         
             
             
         
       
       wherein Z 3  represents 2-hydroxyphenyl group which may be substituted in the 5-position or 2-acetoxyphenyl group which may be substituted in the 5-position, E 3  represents a group represented by the following formula:  
       
         
           
           
               
               
           
         
       
       wherein one of R 3e2  and R 3e3  represents hydrogen atom and the other represents a hydrocarbon group which may be substituted or hydroxyl group which may be substituted, and R 3e5  represents a C 2  to C 6  hydrocarbon group which may be substituted.  
     
   
   
       21 . The compound according to  claim 20  or a salt thereof, or a hydrate thereof or a solvate thereof, wherein Z 3  is 2-hydroxyphenyl group which is substituted with a halogen atom in the 5-position or 2-acetoxyphenyl group which is substituted with a halogen atom in the 5-position.  
   
   
       22 . A compound represented by the general formula (I-4) or a salt thereof, or a hydrate thereof or a solvate thereof:  
     
       
         
         
             
             
         
       
       wherein Z 4  represents 2-hydroxyphenyl group which may be substituted in the 5-position or 2-acetoxyphenyl group which may be substituted in the 5-position, E 4  represents a group represented by the following formula:  
       
         
           
           
               
               
           
         
       
       wherein R 4e4  represents a hydrocarbon group which may be substituted, R 4e5  represents a halogen atom, cyano group, an acyl group which may be substituted, or a heterocyclic group which may be substituted.  
     
   
   
       23 . The compound according to  claim 22  or a salt thereof, or a hydrate thereof or a solvate thereof, wherein Z 4  is 2-hydroxyphenyl group which is substituted with a halogen atom in the 5-position or 2-acetoxyphenyl group which is substituted with a halogen atom in the 5-position.