Substituted thiazolidinedione derivatives

Abstract

A compound of formula (I): or a tautomeric form thereof, wherein: R 1 represents a hydrogen atom, C 1-12 alkyl, C 1-12 alkoxy, C 1-12 alkylcarbonyl or arylC 1-12 alkyl; A 1 represents hydrogen or 1 to 4 optional substituents selected from the group consisting of: C 1-12 alkyl, C 1-12 alkoxy, aryl, and halogen; aryl represents phenyl or naphthyl optionally substituted with up to five groups selected from halogen, C 1-12 alkyl, phenyl, C 1-12 alkoxy, haloC 1-12 alkyl, hydroxy, nitro, C 1-12 alkoxycarbonyl, C 1-12 alkoxycarbonyl C 1-12 alkyl, C 1-12 alkoxycarbonyloxy, or C 1-12 alkylcarbonyl: A 2 represents a benzene ring having 1 to 3 optional substituents selected from hydrogen, halogen, C 1-12 alkyl, C 1-12 alkoxy; and M − represents a counter-ion other than the maleate ion.

1. A compound of formula (I): 
                 
 
       or a tautomeric form thereof, wherein:
 R 1  represents a hydrogen atom, C 1-12  alkyl, C 1-12  alkoxy, C 1-12  alkylcarbonyl or arylC 1-12  alkyl;  
 A 1  represents hydrogen or 1 to 4 optional substituents selected from the group consisting of: C 1-12  alkyl, C 1-12  alkoxy, aryl and halogen;  
 aryl represents phenyl or naphthyl optionally substituted with up to five groups selected from halogen, C 1-12  alkyl, phenyl, C 1-12  alkoxy, haloC 1-12  alkyl, hydroxy, nitro, C 1-12  alkoxycarbonyl, C 1-12  alkoxycarbonyl, C 1-12  alkoxycarbonyloxy, or C 1-12  alkylcarbonyl;  
 A 2  represents a benzene ring having 1 to 3 optional substituents selected from hydrogen, halogen, C 1-12  alkyl, C 1-12  alkoxy; and  
 M −  represents a counter-ion other than the maleate ion  
 which is  5 - [ 4   - [ 2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]thiazolidine -   2 , 4   - dione tartaric acid salt or a tautomer of  5   -[   4   - [ 2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]thiazolidine -   2 , 4   - dione tartaric acid salt.   
 
     
     
       2. A process for the preparation of a compound of formula (I)  according to  claim 1 , or a tautomeric form thereof,  which process comprises reacting a compound of formula (II): 
                 
 
       wherein R 1 , A 1 , and A 2  are as defined in relation to formula (I) in  claim 1 , with a source of counter-ion M −  which is defined in relation to formula (I), as defined in  claim 1 
   5 - [ 4   - [ 2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]thiazolidine -   2 , 4   - dione or a tautomeric form thereof with a source of tartarate ion.   
 
     
     
       3. The compound according to  claim 1 , wherein the salt is in a solid form. 
     
     
       4. A pharmaceutical composition comprising a compound according to  claim 1  and at least one pharmaceutically acceptable carrier. 
     
     
       5. The pharmaceutical composition according to  claim 4  comprising an individual isomer of  5 - [ 4   - [ 2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]thiazolidine -   2 , 4   - dione tartaric acid salt or a tautomer of  5   -[   4   - [ 2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]thiazolidine -   2 , 4   - dione tartaric acid salt.   
     
     
       6. The pharmaceutical composition according to  claim 4  comprising a mixture of isomers of  5 - [ 4   - [ 2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]hiazolidine -   2 , 4   - dione tartaric acid salt or a tautomer of  5   - [ 4   -[   2   -( N - methyl - N -(   2   - pyridyl ) amino ) ethoxy]benzyl]thiazolidine -   2 , 4   - dione tartaric acid salt.   
     
     
       7. The pharmaceutical composition according to any one of  claims 4  to  6 , wherein the composition is in a form suitable for oral administration. 
     
     
       8. The pharmaceutical composition according to  claim 7 , wherein the form is chosen from tablets, capsules, and powders. 
     
     
       9. The pharmaceutical composition according to  claim 7 , wherein the form is a tablet. 
     
     
       10. The pharmaceutical composition according to  claim 4 , wherein the composition is in a form suitable for injection. 
     
     
       11. The pharmaceutical composition according to  claim 4 , wherein the composition is in a form suitable for percutaneous absorption. 
     
     
       12. The pharmaceutical composition according to  claim 4 , wherein the at least one pharmaceutically acceptable carrier is chosen from microcrystalline cellulose, starch, sodium starch glycollate, polyvinylpyrrolidone, polyvinylpolypyrrolidone, magnesium stearate, and sodium lauryl sulphate. 
     
     
       13. The pharmaceutical composition according to  claim 4 , wherein the at least one pharmaceutically acceptable carrier comprises a diluent, filler, disintegrant, wetting agent, lubricant, colourant, flavourant, or adjuvant.