Phacetoperane for the treatment of attention-deficit hyperactivity disorder

Abstract

The invention relates to the treatment of an attention deficit hyperactivity disorder (ADHD) with alpha-phenyl(piperidin-2-yl)methanol, or the pharmaceutically acceptable salts and esters thereof, in particular the acetate derivative, more particularly dextrophacetoperane. The invention additionally provides a method of synthesis of the (S,S) enantiomer of alpha-phenyl(piperidin-2-yl)methanol as well as a method of synthesis of dextrophacetoperane.

1 . A method for treating an attention deficit hyperactivity disorder (ADHD) in a patient, which method comprises administering alpha-phenyl(piperidin-2-yl)methanol, or the pharmaceutically acceptable salts and esters thereof. 
     
     
         2 . The method according to  claim 1 , comprising administering the patient with alpha-phenyl(piperidin-2-yl)methyl acetate in the threo form (phacetoperane) or a pharmaceutically acceptable salt thereof. 
     
     
         3 . The method of  claim 2 , wherein said phacetoperane is in its dextrorotatory form. 
     
     
         4 . The method of  claim 2 , wherein said phacetoperane is in its laevorotatory form. 
     
     
         5 . The method of  claim 1 , wherein the patient is an adults. 
     
     
         6 . The method of  claim 1 , wherein alpha-phenyl(piperidin-2-yl)methanol, or a pharmaceutically acceptable salt and ester thereof, is administered by the oral route. 
     
     
         7 . The method of  claim 6 , wherein alpha-phenyl(piperidin-2-yl)methanol, or the pharmaceutically acceptable salt and ester thereof, is in a form suitable for prolonged release. 
     
     
         8 . The method of  claim 6 , wherein alpha-phenyl(piperidin-2-yl)methanol, or a pharmaceutically acceptable salt and ester thereof, is in the form of a combination or of a mixture of microgranules for immediate release, and of microgranules for prolonged release. 
     
     
         9 . A method of preparing the compound of formula (VI) in the form of (S,S) enantiomer: 
       
         
           
           
               
               
           
         
       
       in which R 1  represents a hydrogen or a protecting group, 
       said method comprising reduction of the compound of formula (V) 
       
         
           
           
               
               
           
         
       
       by an alkaline salt of tri-sec-butylborohydride. 
     
     
         10 . A method of preparing the (S,S) enantiomer of alpha-phenyl(piperidin-2-yl)methyl acetate(dextrophacetoperane) or a pharmaceutically acceptable salt thereof, said method comprising the following steps:
 preparation of the compound of formula (VI) in the form of (S,S) enantiomer according to the method defined in  claim 9 , and   acetylation of the compound of formula (VI), optionally followed by deprotection of the amine function of the piperidine group when R 1  is a protecting group.