Esters of thienyl carboxylic acids and amino alcohols and their quaternization products

Abstract

Compounds of the formula of which, in exemplary compounds, the thienyl group is attached via the 2-position and; (a) A is 3alpha-(6beta, 7beta-epoxy)-tropanyl methobromide and R<SUB>1 </SUB>is 2-thienyl; (b) A is 3alpha-(6, 7dehydro)-tropanyl methobromide and R<SUB>1 </SUB>is 2-thienyl; (c) A is 3beta-tropanyl methobromide and R<SUB>1 </SUB>is 2-thienyl; and, (d) A is 3alpha-(N-isopropyl)-nortropanyl methobromide and R<SUB>1 </SUB>is cyclopentyl. There are anticholinergics. Administered by inhalation, they are useful for the treatment of chronic obstructive bronchitis or slight to moderately severe asthma. Administered by the intravenous or oral routes, they are useful for the treatment of vagally induced sinus bradycardia.

We claim:  
     
       1. A compound of the formula 
                 
 
       wherein
 Q is a group of the formula —CH 2 —CH 2 —,  —CH═CH— or 
                 
 
 R and R′ are each independently C 1 -C 4 -alkyl;  
 R 1  is thienyl, phenyl, cyclopentyl or cyclohexyl; and,  
 X −  is a physiologically acceptable anion.  
 
     
     
       2. A compound in accordance with  claim 1 , of the formula 
                 
 
       wherein
 R is CH 3 , C 2 H 5 , n-C 3 H 7 , or i-C 3 H 7 ;  
 R′ is CH 3 ; and  
 R 1 , Q and X −  are as defined in  claim 1 .  
 
     
     
       3. A compound in accordance with  claim 2  wherein R 1  is thienyl. 
     
     
       4. A compound in accordance with  claim 2  wherein X −  is Br −  or CH 3 SO 3   CH 3   SO   3     −   . 
     
     
       5. A compound of the formula 
                 
 
       wherein X −  is a physiologically acceptable anion. 
     
     
       6. A compound of the formula 
                 
 
       wherein X −  is a physiologically acceptable onion. 
     
     
       7. A compound of the formula 
                 
 
     
     
       8. A compound of the formula 
                 
 
       wherein R 1  is 2-thienyl and A is 3α-(6,7-dehydro)-tropanyl methobromide. 
     
     
       9. A compound of the formula 
                   
       wherein R 1  is 2-thienyl and A is 3β-tropanyl methobromide. 
     
     
       10. A compound of the formula 
                   
       wherein R 1  is cyclopentyl and A is 3α-(N-isopropyl)-nortropanyl methobromide. 
     
     
       11. A method for treating chronic obstructive bronchitis which comprises administering, by inhalation, to a subject suffering from the same, a therapeutic amount of a compound in accordance with claims  1 ,  2 ,  3 ,  4 ,  6 ,  7 , or  8 ,  9 ,  10  . 
     
     
       12. A method for treating slight to moderately severe asthma which comprises administering, by inhalation, to a subject suffering from the same, a therapeutic amount of a compound in accordance with claims  1 ,  2 ,  3 ,  4 ,  6 ,  7 ,  8 ,  9 ,  10 . 
     
     
       13. A method for treating vagally induced sinus bradycardia which comprises administering, by the intravenous or oral routes, to a subject suffering from the same, a therapeutic amount of a compound in accordance with claims  1 ,  2 ,  3 ,  4 ,  6 ,  7 , or  8 ,  9 ,  10  . 
     
     
       14. A pharmaceutical composition, for administration by inhalation, suitable for the treatment of chronic obstructive bronchitis or slight to moderately severe asthma , which comprises a compound in accordance with claims  1 ,  2 ,  3 ,  4 ,  6 ,  7 , or  8 ,  9 ,  10  . 
     
     
       15. A pharmaceutical composition for oral administration, suitable for the treatment of vagally induced sinus bradycardia, which comprises a compound in accordance with claims  1 ,  2 ,  3 ,  4 ,  6 ,  7 , or  8 ,  9 ,  10  . 
     
     
       16. A pharmaceutical composition, for intravenous administration, suitable for the treatment of vagally induced sinus bradycardia, which comprises a compound in accordance with claims  1 ,  2 ,  3 ,  4 ,  6 ,  7 , or  8 ,  9 ,  10  . 
     
     
       17. A method for treating chronic obstructive bronchitis which comprises administering, by inhalation, to a subject suffering from the same, a therapeutic amount of a compound in accordance with  claim 5 . 
     
     
       18. A pharmaceutical composition, for administration by inhalation, suitable for the treatment of chronic obstructive bronchitis, which comprises a compound in accordance with  claim 5 . 
     
     
       19. A pharmaceutical composition, for administration by inhalation, suitable for the treatment of chronic obstructive bronchitis, comprising an inhalation powder comprising a compound in accordance with  claim 5 .