Piperazine-substituted benzothiophene derivatives as antipsychotic agents

Abstract

Provided is a superior, novel heterocyclic compound with improved solubility in oil such as sesame oil and benzyl benzoate, which has a broader treatment spectrum, causes less side effects, and is superior in tolerability and Safety, and use thereof. A heterocyclic compound represented by the formula (I) wherein each symbol is as defined in the specification, or a salt thereof.

1 - 11 . (canceled) 
     
     
         12 . A method for treating a disease selected from the group consisting of bipolar disorder type I and bipolar disorder type II comprising administering a heterocyclic compound represented by formula (I) or a pharmaceutically acceptable salt thereof to a human or animal: 
       
         
           
           
               
               
           
         
         wherein 
         A is a lower alkylene group; 
       
       
         
           
           
               
               
           
         
         in the monocyclic heterocycle containing Q is 
       
       
         
           
           
               
               
           
         
         wherein 
         R 2′  is the following group 
       
       
         
           
           
               
               
           
         
         wherein 
         Y 1′  is a lower alkylene group, 
         R 3′  is 
         (1) an alkyl group, 
         (2) a cycloalkyl group optionally substituted by a lower alkyl group, 
         (3) a phenyl group, 
         (4) a phenyl lower alkyl group 
         (5) a lower alkoxy group, 
         (6) a cycloalkyloxy group, 
         (7) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group and a phenyl lower alkyl group, or 
         (8) a piperidyl group optionally having a piperidyl group; 
       
       
         
           
           
               
               
           
         
         at the 3-position and the 4-position of the bicyclic heterocycle skeleton containing Z and W is —CH═CH— or 
       
       
         
           
           
               
               
           
         
         wherein R 6  and R 7  are the same or different and each is a hydrogen or a lower alkyl group; 
       
       
         
           
           
               
               
           
         
         wherein 
         R 2  is a hydrogen or 
         the following group 
         (1) 
       
       
         
           
           
               
               
           
         
         (2) 
       
       
         
           
           
               
               
           
         
         (3) —Y 3 —O—R 5 , or 
         (4) 
       
       
         
           
           
               
               
           
         
         wherein 
         Y 1′  is a lower alkylene group optionally substituted by 
         (1) a lower alkoxycarbonyl group or 
         (2) a lower alkyl group, 
         Y 2  is a lower alkylene group, 
         Y 3  is a single bond or a lower alkylene group optionally substituted by a lower alkyl group, 
         R 3  is 
         (1) an alkyl group, 
         (2) a halogen-substituted lower alkyl group, 
         (3) an alkenyl group, 
         (4) an amino lower alkyl group, 
         (5) a cycloalkyl group, 
         (6) a phenyl group, 
         (7) a phenyl lower alkyl group, 
         (8) a piperidyl group optionally having 1 or 2 substituents selected from the group consisting of a lower alkyl group and a piperidyl group, 
         (9) a halogen-substituted piperidyl group, 
         (10) a morpholinyl group, 
         (11) a pyrrolidinyl group, 
         (12) a tetrahydropyranyl group, 
         (13) a furyl group, 
         (14) a thienyl group, 
         (15) a pyridyl group, 
         (16) a pyrimidinyl group, 
         (17) a pyridazinyl group, 
         (18) a benzofuryl group, 
         (19) a quinolyl group, 
         (20) a lower alkoxycarbonyl lower alkyl group, 
         (21) a lower alkoxy lower alkoxy lower alkyl group, 
         (22) a lower alkoxy lower alkoxy lower alkoxy lower alkyl group, 
         (23) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group, a cycloalkyl group, a cycloalkyl lower alkyl group, a lower alkenyl group, a halogen-substituted lower alkyl group, a lower alkoxy group, a lower alkoxy lower alkyl group, a lower alkoxycarbonyl lower alkyl group, a phenyl lower alkyl group, a phenyl lower alkoxy group, a furyl lower alkyl group, a pyridyl lower alkyl group, a hydroxy-substituted lower alkyl group, 
         (24) an amino lower alkyl group optionally having a lower alkylcarbonyl group, 
         (25) a piperazinyl group optionally having a lower alkyl group, or 
         (26) the following group 
       
       
         
           
           
               
               
           
         
         wherein Ac is an alkylene group, and other symbols are as defined above, 
         R 4  is 
         (1) an alkyl group, 
         (2) a phenyl group, 
         (3) a phenyl lower alkyl group, 
         (4) a halogen-substituted lower alkyl group, or 
         (5) a cycloalkyl group, 
         R 5  is 
         (1) a hydrogen, 
         (2) a lower alkyl group, 
         (3) a halogen-substituted lower alkyl group, 
         (4) a phenyl lower alkyl group, 
         (5) a phenyl lower alkoxy lower alkyl group, 
         (6) a tri-lower alkylsilyl group, 
         (7) a tetrahydropyranyl group, or 
         (8) a phosphono group, 
         R 10  is 
         (1) an alkenyl group, 
         (2) a phenyl lower alkyl group, 
         (3) a hydroxy-substituted lower alkyl group, 
         (4) a cycloalkyl group, 
         (5) an amino lower alkyl group optionally having 1 or 2 substituents selected from the group consisting of an amino lower alkylcarbonyl group and a lower alkylcarbonyl group, 
         (6) a pyrrolidinyl group optionally having an amino lower alkylcarbonyl group, 
         (7) an alkoxy group, 
         (8) a lower alkoxy lower alkoxy lower alkyl group, 
         (9) a lower alkoxy lower alkoxy lower alkoxy lower alkyl group, 
         (10) a phenyl lower alkoxy group, 
         (11) an amino group optionally having 1 or 2 substituents selected from the group consisting of an alkyl group, a hydroxy-substituted lower alkyl group and a phenyl lower alkyl group, 
         (12) a morpholino group, 
         (13) a piperazinyl group optionally having a lower alkyl group, 
         (14) a piperidyl group optionally having a piperidyl group, or 
         (15) a cycloalkyloxy group; 
         provided when 
       
       
         
           
           
               
               
           
         
       
       then
 R 2  is not a hydrogen. 
 
     
     
         13 . The method according to  claim 12 , wherein the heterocyclic compound represented by formula (I) is a compound represented by formula (II) 
       
         
           
           
               
               
           
         
         wherein each symbol is as defined in claim  1 . 
       
     
     
         14 . The method according to  claim 12 , wherein the heterocyclic compound represented by formula (I) is a compound represented by formula (III) 
       
         
           
           
               
               
           
         
         wherein 
       
       
         
           
           
               
               
           
         
         wherein 
         R 2a  is 
         the following group 
         (1) 
       
       
         
           
           
               
               
           
         
         (2) 
       
       
         
           
           
               
               
           
         
         wherein 
         Y 1a  is a lower alkylene group, 
         Y 2a  is a lower alkylene group, 
         R 3a  is 
         (1) an alkyl group, 
         (2) a cycloalkyl group, 
         (3) a piperidyl group optionally having 1 or 2 substituents selected from the group consisting of a lower alkyl group, 
         (4) a tetrahydropyranyl group, 
         (5) a lower alkoxycarbonyl lower alkyl group, 
         (6) a lower alkoxy lower alkoxy lower alkyl group 
         (7) an amino lower alkyl group optionally having a lower alkylcarbonyl group, or 
         (8) the following group 
       
       
         
           
           
               
               
           
         
         wherein Ac′ is an alkylene group, Y 1a  is a lower alkylene group and other symbols are as defined in claim  1 , 
         R 4a  is 
         (1) an alkyl group, or 
         (2) a cycloalkyl group; and 
         A is a lower alkylene group. 
       
     
     
         15 . The method according to  claim 13 , wherein
 R 2  is   the following group   (1)   
       
         
           
           
               
               
           
         
       
       or
 (2) 
 
       
         
           
           
               
               
           
         
         wherein 
         Y 1a  is a lower alkylene group, 
         Y 2a  is a lower alkylene group, 
         R 3a′  is 
         (1) an alkyl group, 
         (2) a cycloalkyl group 
         (3) a piperidyl group optionally having 1 or 2 substituents selected from the group consisting of a lower alkyl group, 
         (4) a tetrahydropyranyl group, 
         (5) a lower alkoxycarbonyl lower alkyl group, 
         (6) a lower alkoxy lower alkoxy lower alkyl group 
         (7) an amino lower alkyl group optionally having a lower alkylcarbonyl group, 
         R 4a  is 
         (1) an alkyl group, or 
         (2) a cycloalkyl group.