Protein kinase c activity enhancer containing alkyl ether derivative or salt thereof

Abstract

Disclosed is a protein kinase C enhancer characterized by containing a benzothiophene alkyl ether derivative represented by the general formula below or a salt thereof. (In the formula, R 1 and R 2 may be the same or different and represent one or more groups selected from a hydrogen atom, a halogen atom, an alkyl group, an aryl group, an aralkyl group, an alkoxy group, an aryloxy group, an alkenyl group, an amino group, a heterocyclic group, an optionally protected amino group, a hydroxyl group, a carboxyl group, an oxo group and the like; R 3 represents an alkylamino group, an amino group, a hydroxyl group or the like; and m and n may be the same or different and represent an integer of 1-6.) This protein kinase C enhancer is useful for treatment or prevention of various diseases associated with protein kinase C.

1 - 5 . (canceled) 
     
     
         6 . A method for treating or preventing a disease where protein kinase C is involved, comprising administering to a subject in need thereof a benzothiophene alkyl ether compound represented by general formula (I): 
       
         
           
           
               
               
           
         
       
       wherein,
 R 1  and R 2  may be the same or different and each represents one or more groups selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted alkyl, aryl, aralkyl, alkoxy, aryloxy, alkylthio, arylthio, alkenyl, alkenyloxy, amino, alkylsulfonyl, arylsulfonyl, carbamoyl or heterocyclic group, an optionally protected amino, hydroxyl or carboxyl group, a nitro group, and an oxo group; 
 R 3  represents an optionally substituted alkylamino group, or an optionally protected amino or hydroxyl group; and 
 m and n may be the same or different and each represents an integer of 1 to 6, or 
 a pharmaceutically acceptable salt thereof. 
 
     
     
         7 . The method of  claim 6 , comprising administering a compound of formula (I) where R 1  is H; or a pharmaceutically acceptable salt thereof. 
     
     
         8 . The method of  claim 6 , comprising administering a compound of formula (I) where R 2  is H, halogen, or alkoxy; or a pharmaceutically acceptable salt thereof. 
     
     
         9 . The method of  claim 6 , comprising administering a compound of formula (I) where R 3  is hydroxyl; or a pharmaceutically acceptable salt thereof. 
     
     
         10 . The method of  claim 6 , comprising administering a compound of formula (I) where m is 2; or a pharmaceutically acceptable salt thereof. 
     
     
         11 . The method of  claim 6 , comprising administering a compound of formula (I) where n is 2 or 3; or a pharmaceutically acceptable salt thereof. 
     
     
         12 . The method of  claim 6 , comprising administering a compound of formula (I) where R1 and R2 are H, R3 is hydroxyl, m is 2 and n is 3; or a pharmaceutically acceptable salt thereof. 
     
     
         13 . The method of  claim 6 , comprising administering 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol (“T-817”); or a pharmaceutically acceptable salt thereof. 
     
     
         14 . A method for reducing the severity of a disease or disorder that is ameliorated by enhancing protein kinase C activity comprising:
 administering to a subject in need thereof a benzothiophene alkyl ether compound represented by general formula (I):   
       
         
           
           
               
               
           
         
       
       wherein,
 R 1  and R 2  may be the same or different and each represents one or more groups selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted alkyl, aryl, aralkyl, alkoxy, aryloxy, alkylthio, arylthio, alkenyl, alkenyloxy, amino, alkylsulfonyl, arylsulfonyl, carbamoyl or heterocyclic group, an optionally protected amino, hydroxyl or carboxyl group, a nitro group, and an oxo group; 
 R 3  represents an optionally substituted alkylamino group, or an optionally protected amino or hydroxyl group; and 
 m and n may be the same or different and each represents an integer of 1 to 6, or 
 a pharmaceutically acceptable salt thereof. 
 
     
     
         15 . The method of  claim 14 , wherein in said benzothiophene alkyl ether compound or salt thereof R 1  is a hydrogen atom, and R 2  is a hydrogen atom, a halogen atom, or an alkoxy group, or a pharmaceutically acceptable salt thereof. 
     
     
         16 . The method of  claim 14 , wherein in said benzothiophene alkyl ether compound or pharmaceutically acceptable salt thereof m is 2 and n is 2 or 3. 
     
     
         17 . The method of  claim 14 , wherein in said benzothiophene alkyl ether compound or pharmaceutically acceptable salt thereof R 2  is a hydrogen atom, R 3  is a hydroxyl group, and n is 3. 
     
     
         18 . The method of  claim 14  that comprises administering 1-(3-(2-(1-benzothiophen-5-yl)ethoxy)propyl)azetidin-3-ol or a pharmaceutically acceptable salt thereof. 
     
     
         19 . A method for enhancing protein kinase C activity comprising:
 administering to a subject in need thereof a benzothiophene alkyl ether compound represented by general formula (I):   
       
         
           
           
               
               
           
         
       
       wherein,
 R 1  and R 2  may be the same or different and each represents one or more groups selected from the group consisting of a hydrogen atom, a halogen atom, an optionally substituted alkyl, aryl, aralkyl, alkoxy, aryloxy, alkylthio, arylthio, alkenyl, alkenyloxy, amino, alkylsulfonyl, arylsulfonyl, carbamoyl or heterocyclic group, an optionally protected amino, hydroxyl or carboxyl group, a nitro group, and an oxo group; 
 R 3  represents an optionally substituted alkylamino group, or an optionally protected amino or hydroxyl group; and 
 m and n may be the same or different and each represents an integer of 1 to 6, or 
 a pharmaceutically acceptable salt thereof.