Substituted thiazolidined derivative, process for its preparation and its pharmaceutical use

Abstract

A hydrate of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl)thiazolidine-2,4-dione, maleic acid salt, characterized in that it: (i) comprises water in the range of from 0.3 to 0.6 molar equivalents; and (ii) provides an infra red spectrum containing peaks at 1757, 1331, 1290, 1211 and 767 cm −1 ; and/or (iii) provides a Raman spectrum containing peaks at 1758, 1610, 1394, 1316 and 1289 cm −1 ; and/or (iv) provides a solid state nuclear magnetic resonance spectrum containing chemical shifts substantially as set out in Table I herein; and/or (v) provides an X-ray powder diffraction (XRPD) pattern substantially as set out in FIG. IV herein; a process for the preparation of such a compound, a pharmaceutical composition containing such a compound and the use of such a compound or composition in medicine.

1 . A hydrate of 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt characterised in that it: 
 (i) comprises water in the range of from 0.3 to 0.6 molar equivalents; and    (ii) provides an infra red spectrum containing peaks at 1757, 1331, 1290, 1211 and 767 cm −1 ; and/or    (iii) provides a Raman spectrum containing peaks at 1758, 1610, 1394, 1316 and 1289 cm −1 ; and/or    (iv) provides a solid state nuclear magnetic resonance spectrum containing chemical shifts substantially as set out in Table I; and/or    (v) provides an X-ray powder diffraction (XRPD) pattern substantially as set out in FIG. IV.    
     
     
         2 . A hydrate according to  claim 1 , wherein the water content is in the range of from 0.3 to 0.5 molar equivalents.  
     
     
         3 . A hydrate according to  claim 1  or  claim 2 , which provides an infra red spectrum substantially in accordance with FIG. I.  
     
     
         4 . A hydrate according to any one of  claims 1  to  3 , which provides a Raman spectrum substantially in accordance with FIG. II.  
     
     
         5 . A hydrate according to any one of  claims 1  to  4 , which provides a solid state nuclear magnetic resonance spectrum substantially in accordance with FIG. III.  
     
     
         6 . A hydrate according to any one of  claims 1  to  5 , which provides an X-ray powder diffraction (XRPD) pattern substantially as set out in FIG. IV.  
     
     
         7 . A hydrate according to any one of  claims 1  to  6 , in isolated form.  
     
     
         8 . A hydrate according to any one of  claims 1  to  7 , in pure form.  
     
     
         9 . A hydrate according to any one of  claims 1  to  8 , in crystalline form.  
     
     
         10 . A compound in the form of a rehydratable form of a hydrate according to any one of  claims 1  to  9 .  
     
     
         11 . A process for preparing a hydrate according to  claim 1 . characterised in that 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2, 4-dione, maleic acid salt is crystallised from aqueous ethanol.  
     
     
         12 . A process according to  claim 11 , wherein the aqueous ethanol contains from 2% to 15% of water by volume.  
     
     
         13 . A pharmaceutical composition comprising an effective, non-toxic amount of a hydrate according to  claim 1  and a pharmaceutically acceptable carrier therefor.  
     
     
         14 . A hydrate according to  claim 1 , for use as an active therapeutic substance.  
     
     
         15 . A hydrate according to  claim 1 , for use in the treatment and/or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof.  
     
     
         16 . The use of Hydrate for the manufacture of a medicament for the treatment and/or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof.  
     
     
         17 . A method for the treatment and/or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and certain complications thereof, in a human or non-human mammal which comprises administering an effective, non-toxic, amount of Hydrate to a human or non-human mammal in need thereof.