Thiazoline acid derivatives

Abstract

Phenyl- and pyridyl-substituted thiazoline acid derivatives useful in diagnosing and treating pathological conditions associated with an excess of trivalent metals in humans and animals.

1. A compound of the formula: 
                 
 
       wherein:
 Z is CH or N;  
 R is HI or acyl;  
 R 1 , R 2 , R 3  and R 5  may be the same or different and represent H, alkyl or hydrocarbyl arylalkyl having up to 14 carbon atoms;  
 R 4  is H or alkyl having 1-4 carbon atoms with the proviso that:  
 R 4  is alkyl having 1-4 carbon atoms when  
 Z is CH, R 5  is H and R 4 O is attached to the carbon atom labelled 4; and  
   that R   5    is H, when Z is CH, R, R   1   , R   2   , R   3    and R   4    are each H and R   4   O is attached to the carbon atom labeled  3 ;  a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof.  
 
     
     
       2. A compound of  claim 1  wherein Z is N and R=R 1 =R 2 =R 3 =R 4 =R 5 =H. 
     
     
       3. A compound of  claim 1  wherein Z is CH, R=R 1 =R 2 =R 3 =R 5 =H, and R 4  is alkyl having 1-4 carbon atoms. 
     
     
       4. A compound of  claim 3  wherein R 4  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or t-butyl . 
     
     
       5. A compound of  claim 1  wherein Z is N, R=R 1 =R 2 =R 3 =R 5 =H, and R 4  is alkyl having 1-4 carbon atoms. 
     
     
       6. A compound of  claim 5  wherein R 4  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or t-butyl . 
     
     
       7. A compound of  claim 1  having the formula: 
                 
 
       wherein:
 Z, R, R 1 , R 2 , R 3 , R 4  and R 5  have the meanings ascribed thereto in  claim 1 ;  
 
       a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof. 
     
     
       8. A compound of  claim 7  wherein Z is N and R=R 1 =R 2 =R 3 =R 4 =R 5 =H. 
     
     
       9. A compound of  claim 7  wherein Z is CH, R=R 1 =R 2 =R 3 =R 5 =H, and R 4  is alkyl having 1-4 carbon atoms. 
     
     
       10. A compound of  claim 9  wherein R 4  is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl or t-butyl . 
     
     
       11. A compound of  claim 7  wherein Z is N, R=R 1 =R 2 =R 3 =R 5 =H, and R 4  is alkyl having 1-4 carbon atoms. 
     
     
       12. A compound of  claim 11  wherein R 4  is methyl, ethyl, n-propyl, isopropyl, or t-butyl . 
     
     
       13. A compound of claim  7   1  wherein Z is CH, R=R 4 =R 1 =R 2 =R 5 =H, and R 3  is alkyl having 1-4 carbon atoms. 
     
     
       14. A compound of claim  7   1  wherein Z is CH, R=R 4 =R 1 =R 2 =R 5 =H, and R 3  is alkyl having 1-4 carbon atoms. 
     
     
       15. A compound of claim  7   1  wherein Z is CH, R 4 =R 3 =R 2 =R 5 =H, and R 1  is alkyl having 1-4 carbon atoms. 
     
     
       16. A compound of  claim 7  wherein Z is N, R=R 4 =R 1 =R 2 =R 5 =H, and R 3  is alkyl having 1-4 carbon atoms. 
     
     
       17. A compound of  claim 7  wherein Z is N, R=R 4 =R 1 =R 3 =R 5 =H, and R 2  is alkyl having 1-4 carbon atoms. 
     
     
       18. A compound of  claim 7  wherein Z is N, R=R 4 =R 3 =R 2 =R 5 =H, and R 1  is alkyl having 1-4 carbon atoms. 
     
     
       19. An optically pure compound of  claim 1  or  7 . 
     
     
       20. An (S)-enantiomer compound of  claim 7  having the formula: 
                   
       a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof. 
     
     
       21. An (S)-enantiomer compound of  claim 7  having the formula: 
                 
 
       a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof. 
     
     
       22. An (S)-enantiomer compound of  claim 7  having the formula: 
                 
 
       a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof. 
     
     
       23. An (R)-enantiomer compound of  claim 7  having the formula: 
                   
       
        
       
     
     
       24. An (R)-enantiomer compound of  claim 7  having the formula: 
                 
 
       a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof. 
     
     
       25. An (R)-enantiomer compound of  claim 7  having the formula: 
                 
 
       a salt thereof with a pharmaceutically acceptable acid or a pharmaceutically acceptable complex thereof. 
     
     
       26. A pharmaceutical composition in unit dosage form for treating a pathological condition in a human or non-human animal that is associated with an excess of a trivalent metal, ion or compound thereof comprising a therapeutically effective amount of a compound according to  claim 1  or  7  and a pharmaceutically acceptable carrier therefor. 
     
     
       27. A method of preventing or treating a pathological condition in a human or non-human animal that is associated with an excess of a trivalent metal, ion or compound thereof comprising administering to said animal a therapeutically effective amount of a compound according to  claim 1  or  7 .