Isoindoline derivatives

Abstract

Provided is a novel isoindoline compound of the formula (I): The compound is useful for anesthesia by inducing sedation in a mammal.

1 . A compound represented by formula (I): 
     
       
         
         
             
             
         
       
       wherein R 1 s are the same or different 2 groups, each of them is selected from the group consisting of C1-3 alkyl; 
       X is oxygen or sulfur; 
       R 2  is selected from the group consisting of phenyl, benzyl, pyridyl, pyridylmethyl, pyrimidinyl, cyclohexyl, methylpiperazinyl, indanyl, 1,3-benzodioxolyl and naphthyl, all of which may optionally be substituted; provided that when R 2  is phenyl, the 3- and 4-positions of the phenyl moiety are not substituted by alkoxy groups at the same time; 
          represents a single bond or double bond; and 
       L is 
     
     
       
         
         
             
             
         
       
     
     wherein W is oxygen or sulfur atom, A is a group represented by formula (J) 
     
       
         
         
             
             
         
       
     
     wherein R 3  is selected from the group consisting of hydrogen, linear or branched C1-8 alkyl, C1-3 alkyl substituted by at least one fluorine atoms, cyclopentyl, cyclohexyl, cycloheptyl, cyclohexylmethyl, benzyl, 2-pyridyl and 2-pyrimidinyl groups, 
     n″ is an integer of 0-3; or 
     
       
         
         
             
             
         
       
     
     wherein R 3  is as defined above;
 or a salt thereof. 
 
   
   
       2 . The compound of  claim 1 , wherein R 1 s are selected from the group consisting of methyl and ethyl. 
   
   
       3 . The compound of  claim 2 , wherein R 1  is 5,6-dimethyl. 
   
   
       4 . The compound of  claim 1 , wherein R 2  is an optionally substituted phenyl or an optionally substituted pyridyl. 
   
   
       5 . The compound of  claim 1 , which is represented by the formula 
     
       
         
         
             
             
         
       
     
     wherein R 2  is 
     
       
         
         
             
             
         
       
     
     wherein R 4  is selected from the group consisting of C1-5 alkyl, optionally substituted phenyl and optionally substituted benzyl, and L is 
     
       
         
         
             
             
         
       
     
   
   
       6 . An anesthetic composition for inducing sedative effect and anesthesia in a mammal, comprising an anesthetic effective amount of the compound of  claim 1  and a pharmaceutically acceptable carrier. 
   
   
       7 . The composition of  claim 6 , which is for intravenous injection. 
   
   
       8 . A method for inducing sedative effect and anesthesia in a mammal, comprising the step of administering an anesthetic effective amount of the compound of  claim 1  to the subject in need of anesthesia. 
   
   
       9 . The compound of  claim 1 , wherein L is 
     
       
         
         
             
             
         
       
     
     wherein A, W and n″ are the same as those defined in  claim 1 . 
   
   
       10 . The compound of  claim 9 , wherein R 3  is methyl or isopropyl. 
   
   
       11 . The compound of  claim 9 , which is represented by the formula: 
     
       
         
         
             
             
         
       
     
     wherein R 2  and L are selected from the following combinations: 
     
       
         
               
               
             
                   
               
                 R 2   
                 L 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
           
              
              
              
             
             
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
              
             
          
         
       
     
     or a pharmaceutically acceptable salt thereof. 
   
   
       12 . The compound of  claim 1 , wherein L is 
     
       
         
         
             
             
         
       
     
     wherein R 3  is the same as that defined in  claim 1 . 
   
   
       13 . The compound of  claim 12 , which is represented by the formula: 
     
       
         
         
             
             
         
       
     
     wherein R2 and L are selected from the following combinations: 
     
       
         
               
               
             
                   
               
                 R 2   
                 L 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
                 
                   
                     
                     
                         
                         
                     
                   
                 
                 
                   
                     
                     
                         
                         
                     
                   
                 
               
                   
               
           
              
              
              
             
             
              
              
              
              
             
          
         
       
     
     or a pharmaceutically acceptable salt thereof.