4-Substituted piperidine compound

Abstract

The present invention provides a novel compound having a superior acetylcholinesterase inhibitory action. It provides a compound represented by the formula: (In the formula, R 1 represents a group represented by the formula: (wherein, R 3 , R 4 , R 5 and R 6 are the same as or different from each other and each represents a hydrogen atom, an optionally substituted C 1-6 alkoxy group and the like; and m represents an integer from 0 to 6) and the like; and R 2 represents a hydrogen atom, an optionally substituted C 1-6 alkyl group, an optionally substituted C 2-6 alkenyl group or an optionally substituted C 2-6 alkynyl group), a salt thereof or a hydrate of them.

1 . A method for treating a disease or condition against which an acetylcholinesterase inhibitory action is efficacious, said method comprising: 
 administering a therapeutically effective amount of a compound, a salt thereof, or a hydrate of said compound or salt thereof to a patient in need thereof,    wherein said compound is represented by the formula:                          wherein R 2  of formula (I) represents a hydrogen atom, an optionally substituted C 1-6  alkyl group, an optionally substituted C 1-6  alkenyl group or an optionally substituted C 1-6  alkynyl group, a salt thereof, or a hydrate of said compound or salt thereof; and    R 1  of formula (I) represents any one of group selected from the group consisting of the formulae:                                          wherein R 3 , R 4 , R 5  and R 6  are the same as or different from each other and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted hydrocarbon group, an optionally substituted C 1-6  alkoxy group, a C 1-6  acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group or a C 1-6  thioalkoxy group;    R 7  represents a hydrogen atom or a C 1-6  alkyl group;    the partial structure   represents a single bond or a double bond;    m is 0 or an integer from 1 to 6; and    p represents an integer of 1 or 2.      
     
     
         2 . The method of  claim 1 , wherein said R 1  in said formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a group selected from the group of formulae consisting of  
       
         
           
           
               
               
           
         
         wherein R 3 , R 4 , R 5  and R 6  are the same as or different from each other and each represents a hydrogen atom, a halogen atom, a hydroxyl group, an optionally substituted hydrocarbon group, an optionally substituted C 1-6  alkoxy group, a C 1-6  acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group or a C 1-6  thioalkoxy group; and  
         m is 0 or an integer from 1 to 6.  
       
     
     
         3 . The method of  claim 1  or  2 , wherein said wherein said substituent in the optionally substituted C 1-6  alkyl group, optionally substituted C 2-6  alkenyl group or optionally substituted C 2-6  alkynyl group of R 2  of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is at least one selected from the group consisting of a halogen atom, a hydroxyl group, a nitrile group, a C 1-6  alkyl group, C 3-8  cycloalkyl group, a C 1-6  alkoxy group, a C 1-6  alkoxyalkoxy group, an aryloxy group, an aralkyloxy group, a halogenated C 1-6  alkyl group, a hydroxy C 1-6  alkyl group, a cyano C 1-6  alkyl group, a halogenated C 1-6  alkoxy group, a hydroxy C 1-6  alkoxy group, a cyano C 1-6  alkoxy group, a C 1-6  acyl group, a nitro group, an optionally substituted amino group, an optionally substituted amide group, a mercapto group and a C 1-6  thioalkoxy group.  
     
     
         4 . The method of  claim 1  or  2 , wherein said R 3 , R 4 , R 5  and R 6  in formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, are the same as or different from each other and each represents a hydrogen atom or an optionally substituted C 1-6  alkoxy group.  
     
     
         5 . The method according to  claim 1  or  2 , wherein said R 3 , R 4 , R 5  and R 6  in formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, are the same as or different from each other and each represents a hydrogen atom or an optionally substituted methoxy group.  
     
     
         6 . The method according to  claim 1  or  2 , wherein m of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is an integer of 1.  
     
     
         7 . The method according to  claim 1 , wherein R 1  of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a [(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl group.  
     
     
         8 . The method according to  claim 1  or  2 , wherein R 2  of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a hydrogen atom.  
     
     
         9 . The method according to  claim 1  or  2 , wherein R 2  of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is an optionally substituted C 1-6  alkyl group.  
     
     
         10 . The method according to  claim 1  or  2 , wherein R 2  of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a C 1-6  alkyl group substituted with (1) a halogen atom, (2) a hydroxyl group or (3) a nitrile group.  
     
     
         11 . The method according to  claim 1  or  2 , wherein R 2  of formula (1) of the compound, a salt thereof, or a hydrate of said compound or salt thereof, is a methyl group, an ethyl group, a n-propyl group, an iso-propyl group, a 2-methyl-1-propyl group or a tert-butyl group.  
     
     
         12 . The method according to  claim 1 , wherein said compound, a salt thereof, or a hydrate of said compound or salt thereof, is 
 4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methylpiperidine,    4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-methylpiperidine,    4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-(1-methylethyl)piperidine or    4-[(5,6-dimethoxy-2-fluoro-1-indanon)-2-yl]methyl-1-(2-methylpropyl)piperidine.    
     
     
         13 . The method according to  claim 1  or  2 , wherein the disease or condition is senile dementia, cerebrovascular dementia or attention deficit hyperactivity disorder.