Potentiators of Antibacterial Activity

Abstract

The present invention relates to compounds that potentiate the activity of antibacterials. The present invention also relates to compositions useful in treating bacterial infection in mammals, and methods therewith. The present invention also relates to a method of inhibiting bacterial efflux of an antibiotic, thereby increasing the efficacy of the antibiotic.

1 - 31 . (canceled) 
     
     
         32 . A pharmaceutical composition comprising:
 (i) an antibiotic; and   (ii) the compound:   
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         33 . (canceled) 
     
     
         34 . The composition of  claim 32 , wherein the antibiotic is in a class selected from fluoroquinolone, marcolide, ketolide, rifampin, chloramphenicol, aminoglycoside, oxazolidinone, penicillin, cephalosporin, carbapenem, glycopeptide, sulfonamide, or trimethoprim. 
     
     
         35 . The composition of  claim 34 , wherein the antibiotic is selected from ciproflaxacin, levofloxacin, gatifloxacin, moxifloxacin, ofloxacin, norflaxacin, erythromycin, azithromycin, clarithromycin, telithromycin, rifamipin, tetracycline, minocycline, chloramphenicol, gentamicin, linezolid, penicillin, amoxicillin, ceftriaxone, imipenem, vancomycin, teicoplainin, sulfamethoxazole, isoniazid, ethambutol, para-aminosalicylic acid, mupicorin, or cycloserine. 
     
     
         36 . A method of treating a bacterial infection in a mammal comprising the step of administering to the mammal a composition of  claim 32 . 
     
     
         37 . The method of  claim 36 , wherein the bacterial infection is caused by a gram-positive or a gram-negative bacteria. 
     
     
         38 . The method of  claim 36 , wherein the bacteria is  Salmonella  spp.,  Proteus  spp.,  Acinetobacter  spp.,  Shigella  spp.,  Neisseria  spp.,  Enterobacter  spp.,  Burkholderia  spp.,  Pseudomonas  spp.,  Klebsiella  spp.,  Haemophilus  spp.,  Serratia  spp.,  Providencia  spp.,  Vibrio  spp.,  Francisella  spp.,  Yersinia  spp.,  Actinobacillus  spp.,  Kingella  spp.,  Cardiobacterium  spp.,  Eikenella corrodens, Brucella  spp.,  Bartonella  spp.,  Vibrio  spp.,  Pasteurella  spp.,  Edwardsiella  spp.,  Aeromonas  spp.,  Plesimonas  spp.,  Bartonella  spp.,  Staphylococcus  spp.,  Streptococcus  spp., Enterococci spp.,  Bacillus  spp.,  Corynebacterium spp, Actinomyces  spp.,  Nocardia  spp.,  Rhodococcus  spp.,  Aerococcus  spp.,  Abiotrophia  spp.,  Erysipelotrix  spp.,  Listeria  spp.,  Archanobacterium  spp.,  Mobiluncus  spp.,  Gardnerella  spp.,  Chlamydia  spp.,  Mycoplasma  spp.,  Legionella  spp.,  Coxiella  spp.,  Rickettsia  spp.,  Ureaplasma urealyticum, Borrelia  spp.,  Leptospira  spp.,  Treponema  spp.,  Bacteroides  spp.,  Clostridium  spp.,  Helicobacter  spp.,  Campylobacter  spp.,  Peptostreptococcus  spp.,  Fusobacterium  spp,  Propionibacterium  spp.,  Prevotella  spp.,  Porphyromonas  spp., or  Mycobacteria  spp. 
     
     
         39 . The method of  claim 36 , wherein the bacteria is  Streptococcus  (group A),  Streptococcus  (group C),  Stenotrophomonas maltophilia, Archanobacterium haemolyticum, Chlamydia pneumoniae, Neisseria gonorrhoeae, Corynebacterium diphtheriae, Corynebacterium ulcerans, Mycoplasma pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Moraxella catarrhalis, Pseudomonas aeruginosa, Bordetella pertussis, Bacteroides fragilis, Klebsiella pneumoniae, Mycobacterium tuberculosis, Klebsiella pneumoniae, Burkholderia pseudomallei, Legionella pneumophila, Francisella tularensis, Bacteroides fragilis, Rhodococcus equi, Coxiella burnetti, Rickettsia rickettsii, E. coli, Proteus mirabilis, Salmonella typhi, Salmonella typhimurium, Staphlycoccus saprophyticus, Streptococcus  (group B),  Aerococcus urinae, Morganella morganii, Corynebacterium urealyticum, Ureaplasma urealyticum, Yersinia enterocolitica, Mycobacterium avium, Streptococcus  viridans group,  Streptococcus bovis, Staphylococcus  coagulase-negative,  Stomatococcus mucilaginosus, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Erysipelothrix rhusiopathiae, Coxiella burnetii, Chlamydia psittaci, Corynebacterium diphtheriae, Clostridium perfringens, Borrelia burgdorferi, Neisseria meningitidis, Mycoplasma pneumoniae, Pseudomonas fluorescens, Pseudomonas putida, Serratia marcescens, Campylobacter jejuni, Treponema pallidum, Bacillus cerus, Listeria monocytogenes, Leptospira, Rhodococcus equi, Vibrio vulnicicus, Bacillus anthracis, Francisella tularensis, Pasterurella multocida, Eikenella corrodens, Erysipelothrix rhusiopathiae, Corynebacterium minutissimum, Edwardsiella tarda, Bacillus cereus, Plesimonas shigelloides, Clostridium botulinum, Clostridium perfringrens, Clostridium difficile, Streptococcus  beta-hemolytic groups,  Haemophilus ducreyi, Chlamydia trachomatis, Calymmatobacterium granulomatis, Gardnerella vaginalis, Bartonella henselae, Enterococcus faecalis, Enterococcus faecium, Burkholderia pseudomallei, Treponema carateum,  or  Helicobacter pylori.    
     
     
         40 . The method of  claim 36 , wherein said bacterial infection is, upper respiratory infections, lower respiratory infections, ear infections, pleuropulmonary and bronchial infections, urinary tract infections, intra-abdominal infections, cardiovascular infections, sepsis, CNS infections, skin and soft tissue infections, GI infections, bone and joint infections, genital infections, eye infections, or granulomatous infections. 
     
     
         41 . The method according to  claim 36 , wherein said bacterial infection is selected from pharyngitis, sinusitis, otitis externa, otitis media, bronchitis, empyema, pneumonia, cystitis and pyelonephritis, reneal calculi, prostatitis, peritonitis, dialysis-associated peritonitis, visceral abscesses, endocarditis, myocarditis, pericarditis, transfusion-associated sepsis, meningitis, encephalitis, brain abscess, osteomyelitis, arthritis, genital ulcers, urethritis, vaginitis, cervicitis, conjunctivitis, keratitis, or endophthalmitis. 
     
     
         42 . A method of inhibiting bacterial efflux of an antibiotic, comprising the step of contacting the bacteria with the compound of  claim 32 . 
     
     
         43 . The method of  claim 42 , wherein the antibiotic is selected from ciproflaxacin, levofloxacin, gatifloxacin, moxifloxacin, ofloxacin, norflaxacin, erythromycin, azithromycin, clarithromycin, telitrhomycin, rifamipin and derivatives thereof, tetracycline, minocycline, chloramphenicol, gentamicin, linezolid, penicillin, amoxicillin, ceftriaxone, mupirocin, or imipenem.