Heterocyclic compounds, process for their preparation and pharmaceutical compositions containing them and their use in the treatment of diabetes and related diseases

Abstract

The present invention relates to novel antidiabetic compounds, their tautomeric forms, their derivatives, their stereoisomers, their polymorphs, their pharmaceutically acceptable salts, their pharmaceutically acceptable solvates and pharmaceutically acceptable compositions containing them. This invention particularly relates to novel azolidinedione derivatives of the general formula (I), and their pharmaceutically acceptable salts, pharmaceutically acceptable solvates and pharmaceutical compositions containing them.

1. An intermediate of formula (III) 
                 
 
       where G represents —CHO, —NH 2 , —CH═NOH, —CH 2 NHOH, —CH 2 N(OH)CONH 2  or —CH 2 CH(J)-COOR, wherein J represents hydroxy or halogen atom and R represents hydrogen, or lower alkyl group; and of X, Y and Z represents C═O or C═S and one of the remaining of X, Y and Z represents a group C═ and the other of the remaining of X, Y or Z represents C═C; with a proviso that when cyclic structure represented by X, Y and N form a pyrimidinone group, G does not represent CHO, R 1 , R 2  and R 3  are the substituents either on X, Y or Z or on a nitrogen atom and are the same or different and represent hydrogen atom, halogen, hydroxy or nitro, or optionally substituted groups selected from alkyl, cycloalkyl, alkoxy, cycloalkoxy, aryl, aralkyl, heterocyclyl, heteroaryl, heteroaralkyl, acyl selected from acetyl, propionyl or benzoyl; acyloxy selected from acetyloxy, propionyloxy, or benzoyloxy; hydroxyalkyl, amino, arylamino, arylamino, aminoalkyl, aryloxy, alkoxycarbonyl, alkylamino, alkoxyalkyl, thioalkyl, alkylthio or carboxylic acid or its amides or sulfonic acid or its amides with the provision that when R 1 , R 2  or R 3  is on a nitrogen atom it does not represent hydrogen, halogen, hydroxy, nitro; or substituted or unsubstituted aryloxy, alkoxy, cycloalkoxy, acyloxy selected from acetyloxy, propionyloxy, or benzoyloxy; alkylthio, carboxy or sulfonic acid groups; or any two of R 1 , R 2  and R 3  along with the adjacent atoms to which they are attached may form a substituted or unsubstituted cyclic structure of 4 to 7 atoms, with one or more double bonds, which are carboxylic or optionally contain one or more heteroatoms selected from oxygen, nitrogen and sulfur; the linking group represented by —(CH 2 ) n —O— is attached either through nitrogen atom or through X, Y or Z, where n is an integer ranging from 1-4; and Ar represents an optionally substituted divalent aromatic or heterocyclic group. 
     
     
       2. A pharmaceutical composition which comprises, a compound according to  claim 1  as an effective ingredient and a pharmaceutically acceptable carrier, diluent or excipient. 
     
     
       3. A compound selected from the group consisting of: 
           4   - [ 2   - [ 4   - oxo -   3 , 4   - dihydro -   3   - quinazolinyl]ethoxy]benzaldehyde,    
           4   - [ 2   - [ 2   - Methyl -   4   - oxo -   3 , 4 ,-dihydro -   3   - quinazolinyl]ethoxy]benzaldehyde,    
           4   - [ 2   - [ 2   - Ethyl -   4   - oxo -   3 , 4   - dihydro -   3   - quinazolinyl]ethoxy]benzaldehyde,    
           4   - [ 2   - [ 8   - Aza -   2   - methyl -   4   - oxo -   3 , 4   - dihydro -   3   - quinazolinyl]ethoxy]benzaldehyde,    
           4   - [[ 3   - Methyl -   5   - oxo -   3 , 4 , - dihydro -   2   - quinazolinyl]methoxy]benzaldehyde,    
           4   - [[ 3   - Ethyl -   4   - oxo -   3 , 4 , - dihydro -   2   - quinazolinyl]methoxy]benzaldehyde,    
           4   - [[methyl -   4   - oxo -   1 , 4 , - dihydro -   2   - quinazolinyl]methoxy]benzaldehyde,    
           3   - Methoxy -   4   - [[ 3   - Methyl -   4   - oxo -   3 , 4 ,-dihydro -   2   - quinazolinyl]methoxy]benzaldehyde,    
           4   - [ 2   - [ 2   - Ethyl -   4   - methyl -   6   - oxo -   1 , 6   - dihydro -   1   - pyrimidinyl]ethoxy]benzaldehyde oxime,    
         N - [ 4   - [ 2 [ 2   - Ethyl -   4   - methyl -   6   - oxo -   1 , 6   - dihydro -   1   - pyrimidinyl]ethoxy]benzyl]N - hydroxyurea,    
           4   - [ 2   - [ 2   - Ethyl -   4   - methyly -   6   - oxo -   1 , 6 ,-dihydro -   1   - pyrimidinyl]ethoxy]analine    
           4   - [ 2   -[   2   - Ethyl -   4   - oxo -   3 , 4   ,- dihydro -   3   - quinazolinyl]ethoxy]aniline,    
         Ethyl  2   - bromo -   3   - [ 4   - [ 2   - [ 2   - ethyl -   4   - methyl -   6   - oxo -   1 , 6   - dihydro -   1   - pyrimidinyl]ethoxy]phenyl]propanoate,    
         Ethyl  2   - bromo -   3   - [ 4   - [ 2   - [ 2   - ethyl -   4   - oxo -   3 , 4   - dihydro -   3   - quinazolinyl]ethoxy]phenyl]propionate,    
           3   - [ 4   - [ 2   - [ 2   - Ethyl -   4   - methyl -   6   - oxo -   1 , 6 , - dihydro -   1   - pyrimidinyl]ethoxy]phenyl]-     2   - hydroxypropanoic acid,    
         Ethyl  3   - [ 4   - [ 2   - [ 2   - Ethyl -   4   - methyl -   6   - oxo -1,6,- dihydro -   1   - pyrimidinyl]ethoxy]phenyl ]-   2   - hydroxypropanoate,    
           4   - [ 2   - [ 2 , 5 , 6   - Trimethyl -   4   - oxo -   3 , 4   - dihydro - thieno - [ 2 , 3   - d]pyrimidin -   3   - yl]ethoxy]benzaldehyde,    
           4   - [ 2   - [ 2   - Methyl -   4   - oxo -   3 , 4   - dihydro -   3   - quinazolinyl]ethoxy]aniline, and    
         Ethyl  2   - bromo -   3   - [ 4   - [ 2   - [ 2   - methyl -   4   - oxo -   3 , 4   - dihydro -   3   - quinazolinyl]ethoxy]phenyl]propanoate.