PHACETOPERANE FOR THE TREATMENT OF ATTENTION-DEFICIT HYPERACTIVITY DISORDER

• US 20150038533A1
• Filed: 11/29/2012
• Published: 02/05/2015
• Est. Priority Date: 11/29/2011
• Status: Abandoned Application

• Current Assignee: NLS Pharma AG
• Original Assignee: Assistance Publique - Hopitaux De Paris
• Inventors: Konofal, Eric, Figadere, Bruno
• Application Number:
  US14/360,355
• Publication Number:
  US 20150038533A1
• Time in Patent Office: Days
• US Class Current: 514/317
• CPC Class Codes: A61K 31/445 Non condensed piperidines, e.g. piperocaine
• CPC Class Codes: A61K 31/4458 only substituted in position 2, e.g. methylphenidate
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/20 Hypnotics; Sedatives
• CPC Class Codes: C07D 211/22 by oxygen atoms
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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.

Claims

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:

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 R₁ is a protecting group.