PHACETOPERANE FOR THE TREATMENT OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER
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.