Useful combinations of monobactam antibiotics with beta-lactamase inhibitors

Abstract

A pharmaceutical composition, comprising a combination of an antibiotically active compound of the formula (I): with a β-lactamase inhibitor of one of the formulae (II) to (XIII) are active against Gram-negative bacteria, in particular such bacteria which have become resistant against antibiotics such as aztreonam, carumonam and tigemonam. Optionally the compositions may comprise another β-lactamase inhibitor of one of the formulae (II) to (XIII), particularly of formula (V) or formula (VI).

1 - 45 . (canceled) 
     
     
         46 . A compound of formula Ib: 
       
         
           
           
               
               
           
         
         wherein
 R1 is SO 3 H; 
 R2 is H; 
 R3 is methyl; 
 R4 is C(Rx)(Ry)Z; whereby
 Rx=Ry=H, and Z is a group of one of the formulae 
 
 
       
       
         
           
           
               
               
           
         
         wherein Rd, Re and Rf are individually selected from the group consisting of hydrogen and hydroxy, with the proviso that at least two of Rd, Re and Rf are hydroxy; and
 R5 is hydrogen; 
 
         or a pharmaceutically acceptable salt or inner salt thereof. 
       
     
     
         47 . The compound of  claim 46 , wherein Rd and Re are hydroxy and Rf is hydrogen, or a pharmaceutically acceptable salt or inner salt thereof. 
     
     
         48 . The compound of  claim 46 , wherein R4 is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or inner salt thereof. 
       
     
     
         49 . The compound of  claim 46 , wherein said compound is (3S,4S)-3-{(2Z)-2-(4-aminopyrimidin-2-yl)-3-[(1,5-dihydroxy-4-oxo(2-hydropyridyl))methoxy]-3-azaprop-2-enoylamin}-4-methyl-2-oxoazetidinesulfonic acid. 
     
     
         50 . A pharmaceutical composition, comprising a therapeutically effective amount of a compound according to  claim 46 , or a pharmaceutically acceptable salt or inner salt thereof, and a pharmaceutically acceptable excipient.