2-aminotetralines, a process for their preparation, and pharmaceutical compositions, for the prevention and therapeutic treatment of inflammatory and/or autoimmune pathologies

Abstract

2-Aminotetralines, a process for their preparation, and pharmaceutical compositions, for the prevention and therapeutic treatment of inflammatory pathologies (particularly septic shock) and/or autoimmune pathologies in which the aetiopathogenic role of inflammatory cytokines has been ascertained.

1 . 2-Aminotetralines having formula (I)  
       
         
           
           
               
               
           
         
       
       or their pharmacologically acceptable salts having formula (II)  
       
         
           
           
               
               
           
         
       
       wherein: 
 R and R 1 , are independently, halogen; hydroxy; C1-C4 alkoxy, optionally substituted in position ω with groups OH, NH 2 , NR 3 R 4 , wherein R 3  and R 4  are independently H, C1-C4 alkyl, unsubstituted or substituted in position ω with groups OH, NH 2 ; C1-C4 alkanoyl; C1-C4 alkyl; carbamoyl; carbamoyloxy; amino; amino substituted NR 3 R 4 , where R 3  and R 4  have the aforesaid meanings;  
 R 2  is hydrogen; halogen; hydroxy; methoxy, with the proviso that the case is excluded in which the 2-aminotetraline is a raceme in which (a) R═R 1 ═CH 3 O; R 3 ═H; or (b) R═F; R 1 ═CH 3 O; R 2 ═H; and  
 X −  is the monovalent anion of a pharmacologically acceptable acid.  
 
     
     
         2 . Compound according to  claim 1 , wherein the monovalent anion of a pharmacologically acceptable acid is selected from chloride, bromide, orotate, acid aspartate, acid citrate, acid phosphate, fumarate and acid fumarate, lactate, maleate and acid maleate, acid oxalate, acid sulphate, glucose phosphate, tartrate and acid tartrate.  
     
     
         3 . A compound according to  claim 1  which is selected from: 
 S(−)-2-amino-6-fluoro-7-hydroxytetraline hydrochloride (ST 1237);  
 R(−)-2-amino-6-fluoro-7-hydroxytetraline hydrochloride (ST 1238);  
 (R,S)-2-amino-5,6-difluoro-7-methoxytetraline hydrochloride (ST 1269);  
 (R,S)-2-amino-6-fluoro-7-methyltetraline hydrochloride (ST 1275);  
 (R,S)-2-amino-7-fluoro-6-hydroxytetraline hydrochloride (ST 1267);  
 (R,S)-7-acetyl-2-amino-6-methyltetraline hydrochloride (ST 1274);  
 (R,S)-2-amino-7fluoro-6-methoxytetraline hydrochloride (ST 1262).  
 
     
     
         4 . An orally or parenterally administrable pharmaceutical composition containing a compound of formula I or II and a pharmaceutically acceptable carrier and/or diluent.  
     
     
         5 . An orally or parenterally administrable pharmaceutical composition for the prevention and therapeutical treatment of inflammatory and/or autoimmune pathologies induced by inflammatory cytokines, and which comprises as active ingredient a compound according to  claim 1 ,  2  or  3  and a pharmacologically acceptable excipient.  
     
     
         6 . Composition according to  claim 5 , for the prophylactic and the therapeutical treatment of septic shock.  
     
     
         7 . Composition according to  claim 5 , for preparing a medicament for the therapeutic treatment of rheumatoid arthritis, pancreatitis, inflammatory bowel disease, systemic lupus erythematosus, glomerulonephritis and encephalomyelitis.