Drug containing benzophenone derivative or its salt

Abstract

Pharmaceutical agents characterized by containing benzophenone derivatives represented by the general formula: wherein the each substituent is as defined in the specification, or salts thereof have suppressive effect on RANKL production, suppressive effect on OPG reduction and inhibitory effects on differentiation/activation of osteoclasts, and are extremely useful for treating, for example therapy and/or prevention, of various diseases in which differentiation/activation of osteoclast are involved, such as osteoporosis.

1 . A treating agent of osteoporosis, comprising a benzophenone derivative represented by general formula (I): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  represents a substituted or unsubstituted heterocyclic group, a substituted phenyl group or a substituted or unsubstituted alkyl group; 
 Z represents a substituted or unsubstituted alkylene group; 
 R 2  represents a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted alkoxycarbonyl or heterocyclic carbonyl group or a protected or unprotected carboxyl group; 
 R 3  represents a hydrogen atom, a halogen atom, a cyano group, a nitro group, a protected or unprotected carboxyl group, a protected or unprotected hydroxyl group, a protected or unprotected amino group, a mercapto group, a carbamoyl group or a substituted or unsubstituted alkyl, alkenyl, cycloalkyl, aryl, aralkyl, alkoxy, aryloxy, acyl, alkoxycarbonyl, aryloxycarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, alkylamino, acylamino, alkylsulfonylamino, arylsulfonylamino or heterocyclic group; 
 R 4  represents a substituted or unsubstituted alkoxy, cycloalkyloxy, cycloalkenyloxy, alkyl, cycloalkyl, heterocyclic-oxy or heterocyclic group; 
 R 5  represents a hydrogen atom, a halogen atom or a hydroxyl group, or a salt thereof. 
 
     
     
         2 . The treating agent of osteoporosis according to  claim 1 , wherein R′ is a substituted or unsubstituted heterocyclic group or a substituted phenyl group; R 2  is a carboxyl group that is optionally protected with alkyl group; R 3  is a protected or unprotected hydroxyl group; R 4  is a substituted or unsubstituted cycloalkyloxy group; R 5  is a hydrogen atom; and Z is an alkylene group. 
     
     
         3 . The treating agent of osteoporosis according to  claim 1 , wherein R 1  is a substituted or unsubstituted heterocyclic group; R 2  is a carboxyl group; and R 3  is a hydroxyl group. 
     
     
         4 . The treating agent of osteoporosis according to  claim 1 , comprising 2-(4-morpholinyl)ethyl 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionate or a salt thereof. 
     
     
         5 . The treating agent of osteoporosis according to  claim 1 , comprising 4-((2-(2-carboxyethyl)-4-(4-(cyclopentyloxy)-2-hydroxybenzoyl)phenoxy)methyl)benzoic acid or a salt thereof. 
     
     
         6 . The treating agent of osteoporosis according to  claim 1 , comprising 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((4-(3-hydroxy-5-isoxazolyl)benzyl)oxy)phenyl)propionic acid or a salt thereof. 
     
     
         7 . The treating agent of osteoporosis according to  claim 1 , comprising 3-(5-(4-(cyclopentyloxy)-2-hydroxybenzoyl)-2-((3-hydroxy-1,2-benzisoxazol-6-yl)methoxy)phenyl)propionic acid or a salt thereof. 
     
     
         8 . A RANKL production suppressant, comprising the benzophenone derivative or a salt thereof according to  claim 1  as an active ingredient. 
     
     
         9 . An OPG reduction suppressant, comprising the benzophenone derivative or salt thereof according to  claim 1  as an active ingredient. 
     
     
         10 . A pharmaceutical agent that inhibits RANKL production and suppresses OPG production decrement, comprising the benzophenone derivative or a salt thereof according to  claim 1  as an active ingredient. 
     
     
         11 . An inhibitor of differentiation/activation of osteoclast comprising the benzophenone derivative or a salt thereof according to  claim 1  as an active ingredient.