1,3,4-oxadiazole and 1,3,4-thiadiazole beta-lactamase inhibitors

Abstract

β-Lactamase inhibitor compounds (BLIs) are disclosed, including compounds that have activity against class A, class C or class D β-lactamases. Methods of manufacturing the BLIs, and uses of the compounds in the preparation of pharmaceutical compositions and antibacterial applications are also disclosed.

1 .- 21 . (canceled) 
     
     
         22 . A pharmaceutical composition comprising aztreonam or a pharmaceutically acceptable salt thereof and a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         23 . A method of treating or preventing a bacterial infection comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to  claim 22 . 
     
     
         24 . The method of  claim 23  wherein the bacterial infection is caused by bacteria that produce a class A, class C or class D β-lactamase. 
     
     
         25 . The method of  claim 24  wherein the bacterial infection is caused by bacteria selected from  Acinetobacter  spp.,  Acinetobacter baumannii, Citrobacter  spp.,  Escherichia  spp.,  Escherichia coli, Haemophilus influenzae, Morganella morganii, Pseudomonas aeruginosa, Klebsiella  spp.,  Klebsiella pneumoniae, Enterobacter  spp.,  Enterobacter cloacae, Enterobacter aerogenes, Pasteurella  spp.,  Proteus  spp.,  Proteus mirabilis, Serratia  spp.,  Serratia marcescens , and  Providencia  spp. 
     
     
         26 . The method of  claim 24  wherein the bacterial infection is caused by bacteria that produce a KPC-2 or KPC-3 β-lactamase. 
     
     
         27 . The method of  claim 24  wherein the bacterial infection is caused by bacteria that produce an OXA-15 β-lactamase. 
     
     
         28 . The method of  claim 23  wherein the bacterial infection is caused by β-lactam resistant bacteria. 
     
     
         29 . The method of  claim 23  wherein the aztreonam and the compound of formula (I) are administered together in a single composition. 
     
     
         30 . A pharmaceutical composition comprising meropenem or a pharmaceutically acceptable salt thereof and a compound of the formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         31 . A method of treating or preventing a bacterial infection comprising administering to a subject in need thereof a therapeutically effective amount of the pharmaceutical composition according to  claim 30 . 
     
     
         32 . The method of  claim 31  wherein the bacterial infection is caused by bacteria that produce a class A, class C or class D β-lactamase. 
     
     
         33 . The method of  claim 32  wherein the bacterial infection is caused by bacteria selected from  Acinetobacter  spp.,  Acinetobacter baumannii, Citrobacter  spp.,  Escherichia  spp.,  Escherichia coli, Haemophilus influenzae, Morganella morganii, Pseudomonas aeruginosa, Klebsiella  spp.,  Klebsiella pneumoniae, Enterobacter  spp.,  Enterobacter cloacae, Enterobacter aerogenes, Pasteurella  spp.,  Proteus  spp.,  Proteus mirabilis, Serratia  spp.,  Serratia marcescens , and  Providencia  spp. 
     
     
         34 . The method of  claim 32  wherein the bacterial infection is caused by bacteria that produce a KPC-2 β-lactamase, KPC-3 β-lactamase or an OXA-15 β-lactamase. 
     
     
         35 . The method of  claim 33  wherein the bacterial infection is caused by β-lactam resistant bacteria. 
     
     
         36 . The method of  claim 33  wherein the meropenem and the compound of formula (I) are administered together in a single composition.