Synthetic Antibacterial Compounds and Uses Thereof

Patent metadata

Field	Value
Publication number	US-2022017482-A1
Application number	US-201917296080-A
Country	US
Kind code	A1
Filing date	Nov 20, 2019
Priority date	Nov 21, 2018
Publication date	Jan 20, 2022
Grant date	—

Abstract

Provided herein are synthetic compounds useful for inhibiting bacterial growth and uses thereof. Also provided are pharmaceutical compositions. The compounds and pharmaceutical compositions are useful for inhibiting growth of a bacterium or treating or preventing a bacterial infection.

First claim

1 . A compound having the structure:

or a pharmaceutically acceptable salt thereof, or a compound having the structure:

or a pharmaceutically acceptable salt thereof, or a compound having the structure:

or a pharmaceutically acceptable salt thereof.

2 . (canceled)

3 . (canceled)

4 . A composition comprising (i) an effective amount of a compound or pharmaceutically acceptable salt of a compound of claim 1 and (ii) a pharmaceutically acceptable carrier or vehicle.

5 . (canceled)

6 . (canceled)

7 . The composition of claim 4 , wherein the composition further comprises another antibacterial agent.

8 . The composition of claim 7 , wherein the other antibacterial agent is Amikacin, Apramycin, Gentamicin, Kanamycin, Neomycin, Tobramycin, Paromomycin, Streptomycin, Spectinomycin, Ertapenem, Doripenem, Imipenem/Cilastatin, Meropenem, Cefadroxil, Cefazolin, Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil, Ceftobiprole, Teicoplanin, Vancomycin, Telavancin, Clindamycin, Lincomycin, Lipopeptide, Daptomycin, Azithromycin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Telithromycin, Spiramycin, Aztreonam, Linezolid, Posizolid, Radezolid, Torezolid, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Penicillin G, Temocillin, Ticarcillin, Bacitracin, Colistin, Polymyxin B, Besifloxacin, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Pefloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, Temafloxacin, Mafenide, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Sulfonamidochrysoidine, Demeclocycline, Doxycycline, Minocycline, Oxytetracycline, Tetracycline, Arsphenamine, Chloramphenicol, Fosfomycin, Fusidic acid, Metronidazole, Mupirocin, Platensimycin, Quinupristin/Dalfopristin, Thiamphenicol, Tigecycline, Tinidazole, Trimethoprim, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifabutin, Rifapentine, Fosmidomycin, Pefloxin, Novobiocin, Delafloxacin or Eravacycline, or a pharmaceutically acceptable salt thereof.

9 . The composition of claim 7 , wherein the other antibacterial agent is a cationic peptide.

10 . The composition of claim 9 , wherein the cationic peptide is polymyxin B, polymyxin B nonapeptide, or Colistin.

11 . A method for inhibiting growth of a bacterium, comprising contacting the bacterium with an effective amount of a compound or pharmaceutically acceptable salt of a compound of claim 1 .

12 - 14 . (canceled)

15 . The method of claim 11 , wherein the bacterium is an aerobic bacterium.

16 . The method of claim 11 , wherein the bacterium is an anaerobic bacterium.

17 . The method of claim 11 , wherein the bacterium is a drug-resistant or multidrug-resistant (MDR) bacterium.

18 . The method of claim 11 , wherein the bacterium is a Gram-negative bacterium.

19 . The method of claim 11 , wherein the bacterium is a Gram-positive bacterium.

20 - 29 . (canceled)

30 . The method of claim 11 , wherein the bacterium is a persister bacterium.

31 - 37 . (canceled)

38 . The method of claim 11 , further comprising contacting the bacterium with another antibacterial agent.

39 . The method of claim 38 , wherein the other antibacterial agent is Amikacin, Apramycin, Gentamicin, Kanamycin, Neomycin, Tobramycin, Paromomycin, Streptomycin, Spectinomycin, Ertapenem, Doripenem, Imipenem/Cilastatin, Meropenem, Cefadroxil, Cefazolin, Cefalothin, Cefalexin, Cefaclor, Cefamandole, Cefoxitin, Cefprozil, Cefuroxime, Cefixime, Cefdinir, Cefditoren, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftazidime, Ceftibuten, Ceftizoxime, Ceftriaxone, Cefepime, Ceftaroline fosamil, Ceftobiprole, Teicoplanin, Vancomycin, Telavancin, Clindamycin, Lincomycin, Lipopeptide, Daptomycin, Azithromycin, Clarithromycin, Dirithromycin, Erythromycin, Roxithromycin, Troleandomycin, Telithromycin, Spiramycin, Aztreonam, Linezolid, Posizolid, Radezolid, Torezolid, Amoxicillin, Ampicillin, Azlocillin, Carbenicillin, Cloxacillin, Dicloxacillin, Flucloxacillin, Mezlocillin, Methicillin, Nafcillin, Oxacillin, Penicillin G, Penicillin V, Piperacillin, Penicillin G, Temocillin, Ticarcillin, Bacitracin, Colistin, Polymyxin B, Besifloxacin, Ciprofloxacin, Enoxacin, Gatifloxacin, Gemifloxacin, Levofloxacin, Lomefloxacin, Moxifloxacin, Nalidixic acid, Norfloxacin, Ofloxacin, Pefloxacin, Trovafloxacin, Grepafloxacin, Sparfloxacin, Temafloxacin, Mafenide, Sulfacetamide, Sulfadiazine, Silver sulfadiazine, Sulfadimethoxine, Sulfamethizole, Sulfamethoxazole, Sulfanilimide, Sulfasalazine, Sulfisoxazole, Sulfonamidochrysoidine, Demeclocycline, Doxycycline, Minocycline, Oxytetracycline, Tetracycline, Arsphenamine, Chloramphenicol, Fosfomycin, Fusidic acid, Metronidazole, Mupirocin, Platensimycin, Quinupristin/Dalfopristin, Thiamphenicol, Tigecycline, Tinidazole, Trimethoprim, Clofazimine, Dapsone, Capreomycin, Cycloserine, Ethambutol, Ethionamide, Isoniazid, Pyrazinamide, Rifampicin, Rifabutin, Rifapentine, Fosmidomycin, Pefloxin, Novobiocin, Delafloxacin or Eravacycline, or a pharmaceutically acceptable salt thereof.

40 . The method of claim 38 , wherein the other antibacterial agent is a cationic peptide.

41 . The method of claim 40 , wherein the cationic peptide is polymyxin B, polymyxin B nonapeptide, or Colistin.

42 . The method of claim 38 , wherein the bacterium is a Gram-negative bacterium and the other antibacterial agent is an outer membrane-damaging agent.

43 . (canceled)

44 . (canceled)

45 . A method for treating or preventing a bacterial infection, comprising administering to a subject in need thereof an effective amount of the compound or pharmaceutically acceptable salt of the compound of claim 1 .

46 - 71 . (canceled)

72 . The method of claim 45 , further comprising administering to the subject another antibacterial agent.

73 - 78 . (canceled)

Assignees

• Univ Mcmaster

Inventors

• Brown Eric
• Elhalfawy Omar M
• Farha Maya
• Magolan Jakob
• Gale Robert

Classifications

• A61K31/352

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• A61K31/05

  Phenols {(cannabinoids A61K31/658)} · CPC title

• C07D263/32

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• A61P31/04

  Antibacterial agents · CPC title

• A61K45/06 Primary

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title