Novel compound

Abstract

Piperidine compounds, processes for preparing them, pharmaceutical compositions comprising them and their use in therapy are disclosed.

1 . Paroxetine methanesulfonate.  
     
     
         2 . A compound according to  claim 1  in non-crystalline form.  
     
     
         3 . A compound according to  claim 1  in crystalline form.  
     
     
         4 . A compound according to  claim 3  having inter alia the following characteristic IR peaks: 1603, 1513, 1194, 1045, 946, 830, 776, 601, 554, and 539±4 cm−1.; and/or the following characteristic XRD peaks: 8.3, 10.5, 15.6, 16.3, 17.7, 18.2, 19.8, 20.4, 21.5, 22.0, 22.4, 23.8, 24.4, 25.0, 25.3, 25.8, 26.6, 30.0, 30.2, and 31.6±0.2 degrees 2 theta.  
     
     
         5 . A process for the preparation of a compound as claimed in  claim 1  or  2  by precipitation from a solution of a paroxetine methanesulfonate, spray drying or freeze drying a solution of a paroxetine methanesulfonate, evaporating a solution of a paroxetine methanesulfonate to a glass, or by vacuum drying of oils of a paroxetine methanesulfonate, or solidification of melts of a paroxetine methanesulfonate.  
     
     
         6 . A process for the preparation of a compound as claimed in  claim 3  or  4  by crystallization or re-crystallization from a solution of a paroxetine methanesulfonate in a solvent.  
     
     
         7 . A process according to  claim 5  or  6  in which the solution, oil or melt of a paroxetine methanesulfonate is prepared by chemical modification of a precursor paroxetine methanesulfonate salt.  
     
     
         8 . A process according to  claim 5  or  6  in which the solution, oil or melt of a paroxetine methanesutfonate is prepared by treating paroxetine free base or a labile derivative thereof with methanesulfonic acid or a labile derivative thereof.  
     
     
         9 . A process according to  claim 8  in which the paroxetine free base or a labile derivative thereof is provided in situ from a preceding reaction step in which the paroxetine free base, or a labile derivative thereof, has been formed.  
     
     
         10 . A process according to  claim 8  or  9  in which the labile derivative of paroxetine free base is an organic acid salt thereof and the labile derivative of methanesulfonic acid is an ammonium or amine salt thereof.  
     
     
         11 . A process according to  claim 5  or  6  in which the solution, oil or melt of a paroxetine methanesulfonate is prepared by deprotecting an acid-labile protected paroxetine precursor with methanesulfonic acid.  
     
     
         12 . A process according to any one of  claims 6  to  11  in which the solvent comprises an aromatic hydrocarbon, water, an alcohol, an ester. a ketone, an amide, a heterocyclic amine, a halogenated hydrocarbon, a nitrile, an ether or a mixture thereof.  
     
     
         13 . A process according to  claim 12  in which the solvent comprises toluene an alcohol, an ester, a ketone, a halogenated hydrocarbon, a nitrile, or an ether, optionally in admixture with water, an ether, or a lower alcohol, or mixtures thereof.  
     
     
         14 . A process according to any one of  claims 6  to  13  in which the solvent forms an azeotrope with water and prior to isolation of the product water is removed by azeotropic distillation.  
     
     
         15 . A process according to any one of  claims 6  to  14  in which the crystallisation is promoted by inclusion of an anti-solvent to the solvent.  
     
     
         16 . A process according to  claim 15  in which the anti-solvent is an ether or hexane.  
     
     
         17 . A process according to any one of  claims 6  to  16  in which the cryvstallisation is conducted at elevated temperature followed by controlled cooling.  
     
     
         18 . A process according to any one of  claims 6  to  17  in which crystallisation is induced by the addition of a seed crystal.  
     
     
         19 . A process according to any one of  claims 6  to  17  in which crystallisation is conducted without the addition of a seed crystal.  
     
     
         20 . A pharmaceutical composition comprising a compound according to any one of  claims 1  to  4  and a pharmaceutically acceptable carrier.  
     
     
         21 . A composition according to  claim 20  in which the carrier comprises a disintegrant.  
     
     
         22 . A composition according to  claim 20  or  21  in which the carrier comprises a binder.  
     
     
         23 . A composition according to any one of  claims 20  to  22  in which the carrier comprises a coloring agent.  
     
     
         24 . A composition according to any one of  claims 20  to  23  in which the carrier comprises a flavouring agent.  
     
     
         25 . A composition according to any one of  claims 20  to  24  in which the carrier comprises a preservative.  
     
     
         26 . A composition according to any one of  claims 20  to  25  adapted for oral administration.  
     
     
         27 . A composition according to  claim 26  which is a tablet or capsule.  
     
     
         28 . A composition according to  claim 27  which is a modified oval shaped tablet.  
     
     
         29 . A composition according to any one of  claims 20  to  28  comprising 1 to 200 mg of active ingredient, calculated on a free base basis.  
     
     
         30 . Use of a compound according to any one of  claims 1  to  4  in the manufacture of a medicament for use in the treatment and/or prevention of any one or more of the Disorders.  
     
     
         31 . A method for treating and/or preventing any one or more of the Disorders by administering an effective and/or prophylactic amount of a compound according to any one of  claims 1  to  4  to a sufferer in need thereof.  
     
     
         32 . A 1:1 solvate of paroxetine methanesulfonate with acetonitrile.  
     
     
         33 . Use of paroxetine methanesulfonate as an intermediate in the preparation of the hydrochloride.  
     
     
         34 . A process for preparing paroxetine hydrochloride by converting paroxetine methanesulfonate.  
     
     
         35 . A pack containing a pharmaceutical composition according to any one of  claims 20  to  29 .  
     
     
         36 . A compound according to  claim 3  substantially as hereinbefore described in Example 2.  
     
     
         37 . A compound according to  claim 3  or  32  substantially as hereinbefore described in any one of Examples 3 to 50.  
     
     
         38 . A process according to  claim 34  substantially as hereinbefore described in any one of Examples 51 to 53.  
     
     
         39 . A composition according to  claim 20  substantially as hereinbefore described in Example 54 or 55.