Therapeutic agent for senile dementia

Abstract

A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the following formula [1]: wherein Z is a group of the formula [2]: D is a group of —(CH 2 ) p —A—(CH 2 ) q —; G is =N—, —CH—, etc.; and Ar is an aromatic heterocyclic group, etc.

1 . A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient an imide derivative of the formula [1]:  
       
         
           
           
               
               
           
         
       
       {wherein Z is a group of the formula [2]:  
       
         
           
           
               
               
           
         
       
       (in which B is a carbonyl or a sulfonyl; R 1  R 2 , R 3  and R 4  are independently a hydrogen atom or a lower alkyl, provided that R 1  and R 2 , or R 1  and R 3  may combine each other to form a hydrocarbon ring, or R 1  and R 3  may combine each other to form an aromatic hydrocarbon ring; said hydrocarbon ring may optionally be cross-linked with a lower alkylene or an oxygen atom; said lower alkylene and hydrocarbon ring may optionally be substituted by at least one alkyl; and n is 0 or 1), D is a group of the formula [3]: —(CH 2 ) p —A—(CH 2 ) q — [3] (in which A is a hydrocarbon ring optionally be cross-linked with a lower alkylene or an oxygen atom; said lower alkylene or said hydrocarbon ring may optionally be substituted by at least one alkyl; and p and q are independently 0, 1 or 2), G is N, CH or COH, and —Ar is an aromatic heterocyclic group, an aromatic hydrocarbon group, benzoyl, phenoxy, or phenylthio, or G is a carbon atom, and —Ar is biphenylmethylidene, where said aromatic heterocyclic group, aromatic hydrocarbon group, benzoyl, phenoxy, phenylthio, and biphenylmethylidene may optionally be substituted by at least one group selected from a lower alkyl, a lower alkoxy and a halogen atom}, or an acid addition salt thereof.  
     
     
         2 . The therapeutic/preventive agent for cognitive dysfunctions according to  claim 1 , which is a therapeutic agent for senile dementia.  
     
     
         3 . A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient the imide derivative as disclosed in  claim 1 , wherein —Ar is an aromatic heterobicyclic group, naphthyl, benzoyl, phenoxy or phenylthio, and G is N, CH or COH, or —Ar is biphenylmethylidene, and G is a carbon atom (said aromatic heterobicyclic group, naphthyl, benzoyl, phenoxy, phenylthio and biphenylmethylidene may optionally be substituted by at least one group selected from a lower alkyl, a lower alkoxy and a halogen atom), or an acid addition salt thereof.  
     
     
         4 . The therapeutic/preventive agent for cognitive dysfunctions according to  claim 3 , which is a therapeutic agent for senile dementia.  
     
     
         5 . A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient the imide derivative as disclosed in  claim 1 , wherein —Ar is an aromatic heterocyclic group condensed with a benzene ring, or naphthyl, benzoyl, phenoxy or phenylthio (said aromatic heterocyclic group condensed with a benzene ring, naphthyl, benzoyl, phenoxy, and phenylthio may optionally be substituted by at least one group selected from a lower alkyl, a lower alkoxy and a halogen atom), and G is N, CH or COH, or an acid addition salt thereof.  
     
     
         6 . The therapeutic/preventive agent for cognitive dysfunctions according to  claim 5 , which is a therapeutic agent for senile dementia.  
     
     
         7 . A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient the imide derivative as disclosed in  claim 1 , wherein Z is a group of the formula [4] 
       
         
           
           
               
               
           
         
       
       in which —L— is a single bond or a double bond, E is a lower alkylene optionally substituted by a lower alkyl, or an oxygen atom, R 5  is a hydrogen atom or a lower alkyl, and B is the same as defined in  claim 1;  a group of the formula [5]:  
       
         
           
           
               
               
           
         
       
       in which —L—, E, R 5  and B are as defined above; a group of the formula [6]:  
       
         
           
           
               
               
           
         
       
       in which R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R1 4 , R 15  are independently a hydrogen atom or a lower alkyl, or the adjacent two groups of R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15  may combine each other to form a double bond, and B is as defined above; a group of the formula [7]:  
       
         
           
           
               
               
           
         
       
       in which R 16  and R 17  are independently a hydrogen atom or a lower alkyl, or R 16  and R 17  may combine each other to form a saturated hydrocarbon ring, and R 5  and B are as defined above; or a group of the formula [8]:  
       
         
           
           
               
               
           
         
       
       in which B is as defined above, or an acid addition salt thereof.  
     
     
         8 . The therapeutic/preventive agent for cognitive dysfunctions according to  claim 7 , which is a therapeutic agent for senile dementia.  
     
     
         9 . A therapeutic/preventive agent for cognitive dysfunctions, which comprises as an active ingredient the imide derivative as diclosed in  claim 1 , wherein the compound of the formula [1] is a compound of the formula [9]:  
       
         
           
           
               
               
           
         
       
       or an acid addition salt thereof.  
     
     
         10 . The therapeutic/preventive agent for cognitive dysfunctions according to  claim 9 , which is a therapeutic agent for senile dementia.  
     
     
         11 . The therapeutic/preventive agent for cognitive dysfunctions according to any one of claims  2 ,  4 ,  6 ,  8  and  10 , which is a therapeutic agent for the Alzheimer type dementia.  
     
     
         12 . The therapeutic/preventive agent for cognitive dysfunctions according to any one of claims  2 ,  4 ,  6 ,  8  and  10 , which is a therapeutic agent for the cerebrovascular dementia.